".I am the Surgeon Geneml of the heterosexuals and the homosexuals, of the young and the old, of the moml or the immoml, the married and the unmarrkd. Z don't have the luxury of deciding which side Z want to be on." -C. Everett Koop Z7ze ubshingron Posf Health Magazine 24 March 1987 Report of The Surgeon General's Workshop on Children With HIV Infection And Their Families Presented by the U.S. DEPARTMENT OF HEALTH 8 HUMAN SERVICES Pubk Health Servcce Health Resources and Services Administration Bureau of Health Care Dellvery and Assistance Division of Maternal and Chrld Health In conjunction wtth &i The Children's Hospital of Philadelphia Apnl 6th-9th. 1987 DHHS Pubkatron No. HRS-D-MC 87-1 This book is dedicated to the memory of Samuel Jared Kushnick in testimony of how much "his life has counted" and how well "his voice is heard." i'ke Surgeon General5 Workshop on Children with HIV Infection and Their Families was supported by grants from l7ze Division of Maternal and Child Health-Public Health Service U.S. Department of Health and Human Services This report was edited by Dr. Benjamin K. Silverman The Children's Hospital of Philadelphia and Mr. Anthony Waddell Allied Medical Consultants, Washington, D.C. The photograph of the AIDS virus used in the logo was taken by Mr. Rob13 J. Mum, wt of Pathology, School of Medicine. University of California, Davis, CA 95616 PREFACE This Surgeon General's Workshop on Children with HIV Infection and Their Families provides an opportunity to summarize the current knowledge about AIDS (Acquired Immunodeficiency Syndrome) in children and to make recommenda- tions about future directions in research, prevention, and amelioration of the effects of pediatric AIDS. Surgeon General's Workshops, of which this is the fifth, have been useful vehicles for assembling experts to improve the health of mothers and children. Representatives of major professional and voluntary organizations and from various components of the Department of Health and Human Services insure not only a comprehensive coverage of the subject but also a network to disseminate and implement the recommendations. In the early eighties we realized that children could develop AIDS when it became apparent that this then very mysterious disease could be transmitted by blood transfusions and the administration of blood products to treat hemophilia. Initially it was difficult to distinguish this entity from the rare and puzzling congen- ital immunodeficiency diseases in children. By 1984 the numbers of children with AIDS had begun to escalate, espe- cially in New York City, Newark, and Miami. The Division of Maternal and Child Health first held an ad hoc meeting to try to delineate the nature of the problem in NYC where infants were occupying acute care hospital beds unneces- sarily because no alternative living arrangements were available. DMCH joined other departmental groups in cosponsoring the first National Meeting on Pedi- atric AIDS in November, 1984. Attendees at this meeting agreed that AIDS did occur in children, that the number of children involved was undercounted in the CDC surveillance system, and that infected infants and children and their fami- lies were subject to discrimination and sometimes barred from basic services. Participants expressed concern about seemingly insoluble problems, although some told of initial efforts to solve them. DMCH, the New York State Health Department, and the Albert Einstein College of Medicine cosponsored a second National Pediatric AIDS Meeting held in March, 1986. A larger group-predominantly of physicians but also of other health workers, child welfare workers, and educators-exchanged information about the clinical spectrum and treatment efforts. A new confidence resulted from the increasing knowledge about the etiology and transmission of AIDS. We recog- nized that many generic solutions were applicable to HIV infection. Many could remember when most infections could be managed even without vaccines and antibiotics. It has been especially heartening to hear how the State Health Depart- ment, the Hemophilia Treatment Center, and the local school had worked together in Swansea, Massachusetts, to retain a boy with AIDS in school in a manner that evoked the best instincts of his classmates and their families. This, then, is actually the third national meeting on pediatric AIDS, and is conducted as a Surgeon General's Workshop to bring our best efforts to bear against this new disease. C. Everett Koop, M.D., Sc.D. Surgeon General . . . Ill PLANNING COMMITTEE Planning Committee for the Surgeon Generals Workshop on Children with HIV Infection and Their Families WORKSHOP CHAIRPERSON Stanley A. Plotkin, M.D. Division of Infectious Diseases Children's Hospital of Philadelphia WORKSHOP DIRECTOR John Hutchings, M.D. Division of Maternal and Child Health U.S. Department of Health and Human Services COMMITTEE MEMBERS Organizational Representatives Phillip Brunell, M.D. American Academy of Pediatrics Margaret W. Hiigartner, M.D. National Hemophilia Foundation LaVohn E. Josten, Ph.D., R.N. American Nurses Association Solbritt Murphy, M.D. Association of Maternal and Child Health Directors Richard H. Schwarz, M.D. American College of Obstetricians and Gynecologists Public and Private Representatives Eunice Diaz, MS., M.P.H. Director, Health Promotion and community Affairs White Medical Center, Los Angeles Anna Garcia, M.S.W. University of Miami School of Medicine James Oleske, M.D. College of Medicine and Dentistry of New Jersey iv Public and Private Representatives Wade P. Parks, M.D., Ph.D. University of Miami School of Medicine Gloria Rodriguez, M.S.W. New Jersey State Department of Health Arye Rubinstein, M.D. The Albert Einstein College of Medicine Gwendolyn B. Scott, M.D. University of Miami School of Medicine Diane W. Wara, M.D. University of California-San Francisco Medical School Federal Representatives Department of Health and Human Services C. Everett Koop, M.D., D.Sc. Surgeon General Public Health Service Georgia Buggs Division of Maternal and Child Health Sander G. Genser, M.D., M.P.H. Alcohol, Drug Abuse, and Mental Health Administration Harold Cinzburg, M.D., J.D., M.P.H. National Institute of Allergy and Infectious Diseases/AIDS Program Harry Haverkos, M.D. National Institute of Drug Abuse Martha F. Rogers, M.D. Centers for Disease Control Anne Willoughby, M.D. National Institute of Child Health and Human Development V ChiMren k Hospital of Philadelphia Representatives Stephen D. Barbour, M.D., Ph.D. Division of Infectious Diseases Shirley Bonnem Vice President Stephen W. Nicholas, M.D. Department of Pediatrics Benjamin K. Silverman, M.D. Department of Emergency Medicine vi WORKSHOP PROGRAM Monday, April 6, 1987 Plenary Session The Children's Hospital of Philadelphia Greetings John Hutchings, M.D. Assistant Director Division of Maternal and Child Health Depattment of Health and Human Services Rockville, MD Presiding Welcome Keynote and Charge Stanley A. Plotkin, M.D. Director. Division of Infectious Diseases The Children's Hospital of Philadelphia Edmond F. Notebaert, President and Chief Executive Officer The Children's Hospital Foundation The Children's Hospital of Philadelphia Robert Zimmerman. M.P.H. Acting Deputy Secretary for Public Health Programs Pennsylvania State Department of Health Harriett Williams Deputy Commissioner for Community Health Services City of Philadelphia C. Everett Koop. M.D.. Sc.D. Surgeon General Public Health Service Department of Health and Human Services Global Epidemiology Thomas C. Quinn. M.D., M.S. National Institute of Allergy and Infectious Dwases Associate Professor of Medwine Johns Hopkins University, Baltimore, MD The Human Immunodeficiency Virus Wade P. Parks. M.D., Ph.D. Director of Pediatrics Division of Immunology and Infectious Disease University of Miami School of Medicme Miami, FL Immunology of HIV Infection Arthur J. Ammann. M.D. Director, Collaborative Research Genentech. Inc. South San Francwo, CA Epidemiology and Transmission of Pediatric Infection Martha F. Rogers. M.D. AIDS Program/Center for Infectious Diseases Centers for Disease Control Atlanta. GA Approaches to Prevention of HIV Infection Walter R. Dowdle, Ph.D. Acting Deputy Director (AIDS) Centers for Disease Control Atlanta. GA Natural History of HIV Infection I Natural History of HIV InfectIon II Gwendolyn B. Scott. M.D. Associate Professor of Pcdiatrlcs Head, Division of Infectious Disease and Immunology University of Miami School of MedIcme Miami. FL James Oleske. M.D. Associate Professor Department of Pcduxrlcs College of Medicine and Dentistry of New Jersey Newark. NJ vii Tuesday, April 7, 1987 HIV Transmitted by Blood Products Supporwe Treatment or Pediatric HIV Infection DN~ Abuse and Women's Medical Issues Educatmn to Prevent HIV Infection Management of Children with HIV Infection Vaccine Strategies A Mother's Viewpoint Wednesday, April 8, 1987 Individual Work Group Recommendations Surgeon General's Response Plenary Session Continued Margaret W. Hileanner. M.D. Professor of PedLtrics Director, Division of Pediatric Hematology/Oncology New York Hospital-Cornell Medical Center New York, NY Arye Rubenstein. M.D. Professor of Pediatrics. Mwrobmlogy and Immunolog\ Albert Einstein College of Medicine of Yeshiva Un~verstt) Bronx. NY Constance Et. Wofsy. M.D. Co-Director, AIDS Activities Principal Investigator. Prqect AWARE San Francisco General Hospital San Francisco, CA Karolynn Siegel. Ph.D. Director of Research Department of Social Work Memorial Sloan Kettermg Cancer Center New York, NY Harold M. Ginzburg. M.D.. J.D.. M.P.H Chief, Epidemiology Branch AIDS Program Nauonal Institute of Allergy and Infectious D~reares Bethesda, MD Mary Boland. R.N. M.S.N.. C.P.N.P Director, AIDS Program Children's Hospital of New Jersey Newark, NJ Gerald V. Quinnan. Jr.. M.D. Division of Virology Office of Biologics Research and Review Center for Drugs and Biologics Food and Drug Administration Bethesda, MD Helen G. Kushnick General Management Corporation Los Angeles, CA Individual Work Groups Begin Plenary Session: Work Groups' Summation and Presentation C. Everett Koop, M.D.. Sc.D Close . . . vu1 CONTENTS INTRODUCTION ............................................ SURGEON GENERALS KEYNOTE ADDRESS. ................. EXCERPTS FROM PRESENTATIONS. ......................... The Global Epidemiology of the Acquired Immunodeticiency Syndrome.. .......................................... The Human Immunodeficiency Virus. ...................... The Immunology of Pediatric AIDS. ....................... Transmission of Human Immunodeficiency Virus Infection in the United States. ........................................ Approaches to Prevention of HIV Infection. ................. Natural History of HIV Infection in Children I. .............. Natural History of HIV Infection II. ....................... HIV Transmitted by Blood Products. ....................... Supportive Care and Treatment of Pediatric AIDS. ........... Intravenous Drug Abuse and Women's Medical Issues. ........ Education to Prevent HIV Infection. ....................... Legal Issues Surrounding Medical Care, Treatment, and Research of Children. .................................. Management of the Child with HIV Infection: Implications for Service Delivery. ..................................... Current Developments and Future Prospects for AIDS Vaccines. A Mother's Viewpoint. ................................... WORK GROUP RECOMMENDATIONS. ....................... RESPONSE OF THE SURGEON GENERAL. .................... APPENDICES.. ............................................. A-Panicipants ......................................... B-Work Group Leaders and Recorders. .................... C-Guidelines for Management of HIV. .................... D-Selected Readings. ................................... E-CDC Classification System; Education and Foster Care for Children Infected with HIV ............................ 7 11 13 17 20 22 24 26 29 32 3.5 38 41 44 47 51 71 76 76 86 87 88 91 ix COMMONWEALTH OF PENNSYLVANIA OFFICE OF THE GOVERNOR HARRISBURG GREETINGS: As Governor of the Commonwealth of Pennsylvania, it gives me great pleasure to extend greetings to all those gathered for the AIDS workshop being held by United States Surgeon General, Dr. C. Everett Koop, M.D. at The Children's Hospital of Philadelphia. I applaud all of you for the dedicated and professional efforts you have taken to improve and strengthen pediatric health care. Best wishes for a productive and meaningful workshop. INTRODUCTION AIDS in children has been a sensational but little understood issue. Fear and ignorance have impeded efforts to understand and control the AIDS epidemic in adults, and this has been even more true for children. Children acquire AIDS as a consequence of adult behavior, but they nevertheless have shared general public opprobrium frequently cast on affected patients. As of 30 March 1987, a cumulative total of 471 children nationwide met the strict criteria established by the Centers for Disease Control (CDC) for Acquired Immunodeficiency Syndrome (AIDS) in children. An untold additional number, perhaps two to three times more, are infected with the Human Immunodeficiency Virus (HIV) but do not meet the CDC criteria. It is not generally appreciated that AIDS is only one of the more severe manifestations of infection with HIV. Other children infected with HIV may fall anywhere on a spectrum from being completely asymptomatic through suffering growth and developmental retarda- tion to having multisystem disease known as AIDS-Related Complex (ARC) involving blood, skin, brain, heart, kidneys, and other organs. Both future opportunities for control of HIV infection and the possibilities for future disaster lie in the area of heterosexually transmitted infections in adults and their consequences to children. At present, pediatric infections-other than those acquired previously through HIV contaminated blood products-stem largely from mothers who themselves are intravenous drug users or whose partners either abuse drugs or are bisexual. If the virus continues to spread through these groups, there inevitably will be more heterosexual infections and more transmission to infants, both within and without the drug using and bisexual sectors. The idea for this conference arose from our perception that the attention of the nation needed to be focused on prevention of HIV infection in children and on the difficulties of caring for those children already infected. At the same time, we learned that the Surgeon General was considering convening a workshop specif- ically to deal with issues arising from pediatric AIDS. Accordingly, a series of meetings took place in the summer and fall of 1986 to plan for a conference. In the subsequent months, approximately 200 people were invited to a closed conference, known as the "Surgeon General's Workshop on Children with HIV Infection and Their Families." We made a deliberate effort to convene not only clinical and research physi- cians, but other types of health providers, clergy, economists, educators, media representatives, and parents. Due attention was given to ethnic and geographical representation. The workshop took place at Children's Hospital of Philadelphia on 6-8 April, 1987. The fifteen papers surveying what is known in the field were presented in plenary session. Following are abstracts of the papers presented in the plenary sessions and summaries of the recommendations from the Work Groups. 1 The results set out in these pages exemplify a peculiarly American way of problem-solving: to bring together the informed and the interested, to give each a voice, and to form a consensus which avoids extremes. We believe that these recommendations are both sound and urgent. If we can learn how to deal humanely with HIV-infected children and to prevent new mothers and children from becoming infected, there is still a chance of stopping the AIDS epidemic. For this purpose, the energies of the American people will need to be mobilized in a "moral equivalent of war" to fight against the spread of HIV. Stanley A. Plotkin, M.D. Director, Division of Infectious Diseases The Children's Hospital of Philadelphia Professor of Pediatrics and Microbiology University of Pennsylvania Professor, The Wistar Institute EXCERPT FROM KEYNOTE ADDRESS C. Everett Koop, M.D., D.Sc. Surgeon General, Public Health Service Nearly five years ago I came to Philadelphia to stand before a similar group of concerned Americans and share my concerns about handicapped children and their families. My opening remarks at that Surgeon General's Workshop noted that our task would not be easy. We were to consider very complex issues, such as the emotional, the moral, the medical, the technological, the social, the psycho- logical, and the financial issues associated with the care for handicapped children. I also mentioned the awesome challenge of putting a dollar value on a human life. I wish it were not so, but those remarks are just as appropriate today when we consider yet another problem of major proportion to cope with: the conse- quences of Human Immunodeficiency Virus (HIV) infection in children and adoles- cents. Five years ago little was known about the nature and extent of AIDS. And although we suspected that children would become involved, it was then far from reality. A great deal has changed since that time, as you are well aware. Many of you in this audience have contributed to our expanding knowledge about AIDS or are in some way associated with issues related to this deadly disease. As a result you are familiar with its history. As of the beginning of April 1987, there were among children under 13 years of age 471 reported cases that meet the Centers for Disease Control (CDC) criteria for pediatric AIDS and 139 reported cases among adolescents aged 13 to 19. The nearly 500 cases among young children is double the number of cases reported only a year ago. Sixty percent of those children have already died. Unfortunately, we expect the number of infected children to continue to increase dramatically. By 1991, the Public Health Service estimates that 3,000 children will have suffered from the disease and virtually all will die. As frightening as this may sound, the number is undoubtedly underestimated. We know that HIV infection in children has manifestations that are legion; full-blown CDCdefurition AIDS is only part of the story. As many as 2,000 additional children are reported to have symptoms of the infection, but do not fit the specific diagnostic criteria. It has been found that congenitally acquired HIV infection may affect the infant's central nervous system (CNS) and thus may lead to alterations in growth and development-signs and symptoms not previously identified with AIDS. With recognition of the wide clinical spectrum of HIV infection in children, the CDC has developed a more detailed and exhaustive classification system for the asymptomatic as well as the symptomatic child, the immunologically compromised child, and the children with neurological disease, lung disease, secondary cancer, cardiopathy , and nephropathy We know this disease has many presentations in children and, as our knowledge expands, our public health surveil- lance will continue to reflect this knowledge. The development of blood-screening procedures and methods of heat treating blood-factor products virtually eliminated the risk of new pediatric AIDS cases from blood and blood products. However, some children had earlier acquired 3 AIDS from contaminated blood. These children and their families also need our attention. The burden suffered by these children, some of whom may also have a severe chronic illness like hemophilia, is enormous. About two-thirds of pediatric AIDS cases are the result of transmission from infected mother to child. While there are other modes of transmission of infec- tion to children and adolescents-sexual abuse, drug abuse, and sexual intercourse-our major focus in pediatric AIDS must be on transmission from the infected pregnant woman. Most of these mothers are intravenous drug abusers or sex partners of drug abusers or of bisexual men. As the virus continues its spread among the general population, however, a woman's lack of direct involve- ment with these high risk behaviors will be no guarantee against her infection and transmission to her fetus. Present information suggests that up to 65 % of babies born to infected mothers will contract the disease. The outlook for these children is almost certain death. Currently, there are almost no programs that provide coordinated, community- based care for pediatric HIV-infected patients. There is a lack of foster care place- ment for HIV-infected infants and children. Pediatric units are overwhelmed by the social and medical demands of both ill and well children with HIV infection. There are not enough hospital personnel to provide and coordinate multi- disciplinary inpatient, outpatient, community care, and just plain hugging and playing with these children. Pediatric house staff in some institutions where the prevalence of AIDS is high are concerned that their neonatal experience is skewed because of the large numbers of neonates with AIDS. Many of these children also suffer abandonment by the mother and society. Because of the stigma of AIDS, there are fewer foster homes open to these chil- dren. In fact there have been virtually impenetrable barriers between them and a whole variety of social and public health services. Our infants and children with this dread disease must be afforded a normal and dignified life. They must be nurtured, helped to grow and develop, allowed to interact with peers, attend school, and encouraged to enjoy and participate in all activities of childhood, despite a shortened life span. The AIDS epidemic is imposing severe social and economic burdens on many communities. It will take combined resources from all levels of government and the private sector to meet the increasing costs: of care for an expanding patient population; of educational efforts to reduce high risk behaviors; of maintaining an effective research effort for improved prevention, treatment, and cure; of the social support to juveniles with AIDS and their families to secure the most normal and dignified existence possible. So far I have been focussing on the issues related to children with AIDS and the heartfelt concern we have for these children. Although we have learned a great deal about AIDS in a short time, our knowledge is nevertheless extremely limited. Prudent judgment must continue to guide us. Under all circumstances we must remain committed to providing humane and dignified care, and we must be willing to bear the responsibilities and costs during the short, troubled lives of these children. Let us look at this profound tragedy from yet another perspective. Why is there pediatric AIDS? The overwhelming majority of children with congenital AIDS have this disease because of parental prenatal behaviors. While AIDS can afflict children at all levels of society, it is occurring disproportionately in those who have the least capacity and resources to cope. Over half of all babies born with AIDS are black with one or both parents infected with AIDS. Another 25 percent 4 of all babies born with AIDS are Hispanic. What we are seeing in reference to AIDS, therefore, is more tragic evidence of high-risk pregnancies and births which are most likely to occur among black women. . . who are poor. . . who are not ready for the world of work. . . who may not even have a high school diploma. . .and who do not have ready access to good prenatal and perinatal health care. This population of young women produces a disproportionate number of low- birth-weight babies. Life for these babies is a struggle from "day one". . . and many of them never make it to "day two." This is additional catastrophic news for the black community, already under great economic and social stress. And it's also more evidence of the apparent inability of American society in general to make much headway in helping these young women deal with their own sexuality and their own destinies. Maternal infection with the HIV is preventable and so too is congenitally acquired AIDS. Assembled here today is a group of national experts from the sciences, the professional community, the government, and the community at- large to address a public health problem of great importance to our nation and to all people of the world. President Reagan has recently called AlDS "Public Health Enemy No. 1." As the Surgeon General of the United States Public Health Service, I am asking you to join with the President to bring all of our skill, exper- tise, and resolve to focus attention on the broad range of health concerns related to children suffering from AIDS. Your task for the next several days will be to develop recommendations for a national strategy for reducing the tremendous burden of this devastating condi- tion, especially among our children. I ask that your recommendations give specific attention to the development of an expanded knowledge base, the health resources and services necessary to address the AIDS problem, and the social strategies necessary to assure that our knowledge and resources are best applied in the service of better health for our children. The recommendations that will emerge from this Surgeon General's Workshop can change attitudes by utilizing calmness, confidence, and clarity in what we say. We must be precise in the use of words lest we exacerbate fear which can only lead to discrimination against children. In dealing with the specific problems of pediatric AIDS, we need guidelines for our communities to bring together local officials, health professionals, educators, religious leaders, and parents to develop an interdisciplinary, moral, and just approach for the battle against AIDS. I wish you well and look forward to the fruits of your labors. You really have the opportunity to make a major contribution to our under- standing of pediatric AIDS, and also to the alleviation of some of the burden borne by children with HIV infection and their families. 5 clrY OF PHILADELPHIA w WILSON GCOOE UL\.,.P April 6, 1987 CHILDREN WITH HIV INFECTION (AIDS) AND TREIR FAMILIES WORKSHOP Philadelphia, PA TO ALL IN ATTENDANCE: As Mayor of Philadelphia, I am privileged to extend my best wishes on this most significant workshop, addressing the issue of "Children with HIV Infection (AIDS) and Their Families.' This gathering is a special one, charged with the important task of formulating recommendations to the Surgeon General of the United States, C. Everett Koop, H-D., in helping to set a national policy regarding this growing problem. May all of you in attendance here today be re- newed and encouraged in your efforts through the diverse and informative Workshop sessions. I express my admiration for the commitment and deter- mination of all participants, and I offer my deepest hopes that this workshop will be an unparalleled success in achiev- ing its goals and objectives. Sincerely, g!2mi2Lm W. WILSON GOODE Mayor WWG:hs EXCERPTS FROM PRESENTATIONS THE GLOBAL EPIDEMIOLOGY OF THE ACQUIRED IMMUNODEFICIENCY SYNDROME Thomas C. Quinn, M.D. Introduction Since its initial recognition in 1981, the acquired immunodeficiency syndrome (AIDS) has become a global pandemic. As of 1 March 1987, nearly 42,000 cases had been reported from over 90 countries. Thirty-two thousand cases have been reported in the United States, an additional 3,000 cases in the other countries of the Americas, 4,500 cases in Europe, and 2,600 cases officially reported in Africa-with several thousand suspected and many more unrecognized in that continent alone. Australia and New Zealand had reported 404 cases for Oceania, and 103 cases had been reported from 10 Asian countries. Because of under- reporting, however, these numbers do not reflect accurately the true incidence of AIDS worldwide. The World Health Organization estimates that there are over 100,000 cases of AIDS throughout the world, with a large majority of these cases occurring in North America and Africa. An additional 300,000-500,000 cases of AIDS-related conditions (ARC) and an estimated 5-10 million people world- wide have already been infected with the virus that causes AIDS, the human immunodeficiency virus (HIV). Figure 1. S-10 million This latter group of infected people represents the human reservoir of this infec- tion from which future cases of AIDS will emerge. In the United States, for example, it is estimated that by 1991 over 270,000 cases of AIDS will have devel- oped from the present pool of l-2 million HIV-infected individuals. In that year, over 54,000 deaths will occur from AIDS, and AIDS will be ranked as one of the leading causes of premature death in our society. For other areas, particu- larly Central Africa, where already lo%-15 % of the general population has been infected by the AIDS virus, these numbers will be even greater. With conserva- tive estimates of 20%-30% of HIV-infected people developing AIDS within a 7 five year period, and with an 80% mortality rate two years from time of diag- nosis of AIDS, AJDS has clearly established itself as one of the most serious epidemics of the century. AIDSischaracterizedbytheunusualappearance of life-threatening oppomulistic infections or malignancies occurring in an individual who has a severe depres- sion of the cell-mediated immune system. Under this clinical case definition, 31,834 patients (including 31,381 adults and 453 children) have been reported as AIDS cases to the CDC as of 2 March 1987. Of these patients, 18,835 (57% of adults and 61% of children) are known to have died, including over 80% of those patients diagnosed before January 1985. Since the initial reports of AIDS in early 1981, the number of cases reported for each 6-month period continues to increase. However, the increases are not exponential, as evidenced by the length- ening period of time required to double the number of cases. Cases have now been reported from all 50 States, the District of Columbia, and the 4 U.S. territories. Fifty-three percent of all the cases have been repotted from New York and California, and the incidence rate of AIDS for New York City and San Francisco is approximately 100 cases/lOO,OOO population. Adult Patients Ninety-seven percent of all adult AIDS patients can be placed in a group that suggests the possible means of disease acquisition. Homosexual or bisexual men not known to have used intravenous drugs represent 65% of ah reported cases, or 70% of the male cases. Heterosexual Iv drug users comprise 17% of all cases, including 15 % of the male cases and 5 1 I of the female cases. Homosexual or bisexual men who have used IV drugs comprise 8% of all cases. Persons with hemophilia or coagulation disorders who have received Factor 8 or Factor 9 concentrates represent 1% of all cases. Heterosexual partners of persons with AIDS or at risk for AIDS represent 4 % of all cases, including 2 % of the males and 27 % of the females. The proportion of female AIDS cases in this risk group increased significantly between 1982 and 1986 from 12 % to 27%, a trend which may prove to be a good marker for following patterns in heterosexual transmis- sion. This last category of heterosexual partners also includes those who, without other identifiable risk, were born in countries in which heterosexual transmis- sion is believed to play a major role, such as in Haiti and Africa. Recipients of transfused blood or blood components comprise 2 % of all cases, which represents 1 X of male cases and 10% of the female. For 3% of AIDS patients, the possible means of disease acquisition is undetermined, in these cases primarily due to lack of epidemiologic investigations before death. Table 1. Distriburion of Eriologic Risk FQC~OU in AIDS Patients in the U.S.A. Male (93%) Female (7%) To~Q~ Homosexual or bisexual men (Non-IVDU)* 70% - 65% Homosexual or bisexual men (IVDU) 8% - 8% Heterosexual IVDU 15% 51% 17% Heterosexual partners of persons with AIDS 2% 27% 4% Coagulation disorders 1% >I% 1% Other transfused patients 1% 10% 2% Undetermined risk factor 3% 11% 3% 100% 100% 100% *(IVDU = Intravenous Drug User) (Total 31,381 patients at March 2, 1987) 8 Pediatric Patients The percentages displayed in Table 2 have remained fairly constant in the weekly CDC reports. An additional undetermined number of children with evidence of HIV-infection are not included in these numbers because they do not fit the CDC definition for AIDS. These children are defined as having AIDS-related complex (ARC), not a reportable syndrome at this time. Many, if not all, will progress to AIDS. Table 2. Demographic and Clinical Distribution of Pediatric AIDS Pm.ents < 13 years) AGE: ETIOLOGIC RISK FACTORS: (a) C 5 years (88%) (a) Parent with AIDS or in high-risk category (80%) (b) > 5 years (12%) (b) Blood transfusion (12%) RACE: (c) Concentrate for coagulation disorders (5%) (a) Black (57%) (d) Not known (3%) (b) Hispanic (22%) CLINICAL DIAGNOSIS: (c) white (20%) (a) Pneumocystis carinii pneumonia (52%) SEX: (b) Other opportunistic infection (47%) (a) Male (55%) (c) Kaposi's sarcoma (1%) (b) Female (45%) (Total 453 patients at 2 March 1987) Pediatric patients have been reported from 29 States, the District of Columbia, and Puerto Rico, with 72% of the pediatric patients reported in Florida, New Jersey, and New York. Since the majority of AIDS cases in children are the results of perinatal transmission from the mother, trends in female AIDS cases may also predict future trends for AIDS in children. Other Countries The epidemiology of AIDS in other countries of the Americas, such as Canada and Brazil, and in Europe is quite similar to that described for the United States. The male-to-female ratio is 13 : 1, and there is a predominance of cases occurring among homosexual or bisexual men and intravenous drug users. However, in tropical countries such as in Africa and Haiti, the male-to-female ratio is 1: 1 and the majority of cases are identified among heterosexually active individuals who deny the above risk factors. Currently, an accurate assessment of the exact number of cases and risk factors for transmission among those cases is not entirely feasible, due to these developing countries' lack of resources to support an accurate surveil- lance system. Serologic surveys for HIV infection and preliminary AIDS surveil- lance studies using modified case definition, however, have provided useful information regarding the spread of HIV infection and AIDS in these areas. In areas where international scientific teams have been monitoring AIDS, it is estimated that the annual incidence of AIDS is approximately 200 cases/1OO,CKlO population, a rate twice that observed presently in New York City or San Fran- cisco. The male-to-female ratio of AIDS cases in Central Africa is approximately 1: 1, and the sex and age-specific distribution of AIDS cases reflects patterns Seen with other sexually transmitted diseases in which the incidence and morbidity rates are higher among younger women and older men. Serologic studies have indicated prevalence rates of HIV antibody ranging from 5%-88% for blood donors, 27 %-88 % among female prostitutes, and 2 %-lo% among pregnant women of Central Africa. Longitudinal data on HIV seroprevalence have shown a rapid rise in HIV antibodies among prostitutes in Kenya from 4% in 1980 to 59 % in 1986. These data demonstrate the rapid spread of HIV infection in a high 9 risk heterosexually active group in Africa. Exposure to infected blood transfu- sions and blood-contaminated needles used for medicinal purposes further amplify the transmission of HIV among the general population of these tropical areas. Consequently, the entire Central African population has become at risk, and some natural history studies have already documented there a 1% annual seroconversion rate in a general heterosexual population. As a result of heterosexual transmission, African women of child-bearing age are exposed to HIV. As in U.S. studies, maternal HIV infection appears to be strongly associated with seropositivity among infants in Africa. In one city of Central Africa, approximately 8 9% of all infants are born to seropositive mothers. While it is unclear what percent of these children will acquire HIV infection perina- tally, it is evident that a substantial number of newborn children are presently being infected with HIV. Children in developing countries are also at risk for acquiring HIV infection from unscreened blood transfusions for the anemia associated with malaria, malnutrition, and other endemic diseases, as well as from exposure to blood-contaminated needles and syringes used for medicinal purposes. Thus, it can be anticipated from these data that HIV infection will have a dramatic effect on the general health of these children and potentially on the safety and efficacy of childhood vaccinations. New Viruses This problem in Africa is now being exacerbated by the appearance of addi- tional human retroviruses, referred to as HTLV-IV or LAV-2, or HIV-2, some of which may cause symptomatic disease, including AIDS. Infection with these retroviruses is rapidly spreading throughout West Africa, primarily by heterosexual transmission, blood transfusions, exposure to blood contaminated needles and syringes, and perinatally from mother to infant. Diagnostic assays for HIV-2 are not entirely reliable for detection of infection with these other human retroviruses, and new methods need to be developed rapidly to help control the spread of these retroviruses. Additional studies on the relationship of these human retroviruses to HIV, including genomic and protein comparisons, as well as on the patho- genicity and natural histdry studies, will help facilitate the development of safe and effective vaccines against these human retroviruses. With an estimated 5-10 million people already infected with HIV, and with projections of l-2 million cases of AIDS occurring worldwide over the next several years, it is evident that AIDS has clearly become established as a global pandemic, presenting an unprecedented health problem for our society. Unless control efforts are successful, HIV infection will continue to spread rapidly by sexual, parenteral, and perinatal modes of transmission. Until a safe and effective vaccine is avail- able, prevention of HIV transmission must rely primarily on educational programs, modification of sexual practices, screening of blood transfusions, and intensive counseling of seropositive individuals. Faced with one of the greatest epidemics of our lifetime, we must make prevention and control of HIV infection an inter- national public health priority, requiring the full commitment of the necessary political, financial, and professional resources of all countries. 10 THE HUMAN IMMUNODEFICIENCY VIRUS Wade Parks, M.D., Ph.D. The virus etiologically associated with AIDS is a member of the Family Retroviridae. A defining characteristic of this family of viruses is that they have a dipfoid linear single-stranded RNA genome that is surrounded by a protein capsid. The capsid is surrounded by a lipoprotein envelope. This envelope or coat is covered with viral glycoproteins that are involved in viral entry into suscep- tible cells and is a major target of the host immune system. A unique marker of the Family Retroviridae is the reverse transcriptase which is a part of the virion and which catabolizes the synthesis of DNA from RNA and is thus an RNA- dependent DNA polymerase. The AIDS virus is a member of one of the sub- families of Retroviridae. Figure 1. The subfamily Lentivirinae that contains the AIDS retrovirus includes a number of unglulate viruses associated with chronic, persistent infections in their natural hosts. These include Equine Infectious Anemia (EIA) or "swamp fever" described first in 1904, Visna-the prototypic lentivirus which causes a neurologic disease of sheep, and Caprine Arthritis and Encephalitis Virus (CAEV). The morphology of lentivirus virions is relatively unique with an elongated, bar-shaped nucleoid. Lentiviruses have a slightly larger genome than most retroviruses, and a larger and more highly variable vii-ion external glycoprotein than other retroviruses. Thus far, the reverse transcriptase differs only slightly, preferring a different divalent cation-magnesium-over manganese. 11 The etiologic agent of AIDS was originally termed the Lymphadenopathy- Associated Virus or LAV by Luc Montagnier and his co-workers at the Institut Pasteur in Paris. When Robert Gallo and his colleagues at the National Cancer Institute repeatedly isolated virus from AIDS patients, they referred to their isolates as Human T-Lymphotropic Virus type III, or HTLV-III. Gallo and his group had already described an HTLV-I and HTLV-II, human-infecting members of the Family Retroviridae, subfamily oncovirinae. Hence, the etiologic agent of AIDS was called HTLV-III in this country and LAV in Europe and frequently abbreviated HTLV-IWLAV. More recently, a group of virologists have recom- mended the term, Human Immunodeficiency Virus (HIV), for the AIDS virus. The retrovirus of AIDS has a structure that is similar to other retroviruses. This means that the linearized form can be depicted as bound on either end by two non-coding regions known as long terminal repeats (LTRs). Moving 5' to 3', the gene order is gag, pal, and env between the LTRs. The gag gene encodes for structural proteins of the virus, including the ~24 molecule, which is the most abundant polypeptide of the virion and which is very important as a diagnostic marker in infected patients. The pal gene encodes for the reverse transcriptase, a remarkable polyfunctional molecule which subserves proteolytic, catalytic, and integration activities within newly infected cells. The env gene encodes for the virion surface proteins, which are glycosylated, hence glycoproteins. The trans- membrane protein is known as p4 1E and is the major component of newer recom- binant diagnostic seroassays for detecting infection. The external glycoprotein is known as gp120. The gp120 contains the region that forms the attachment to the viral target, the CD4 molecule that characterizes certain T-lymphocytes. This high affinity ligand interaction is the mechanism by which the virus can infect cells. Antibodies to the gp120 can neutralize viral infectivity. The gp120 has multiple regions that are highly variable in genetic sequence; these regions differ from one virus to another. Thus, the virus varies markedly, enabling the virus to avoid elimination by the host's immune system. Finally, the AIDS retrovirus has some additional genetic features that demon- strate its amazing versatility. Within the virus there are a number of open reading frames that have the capacity to encode for proteins. Two of these have been described: tat and arr. Roth are products of spliced mRNAs and appear to subserve important biological roles for viral replication. The rut gene especially codes for a protein that binds to a very specific region of the 3-LTR and then enhances transcription. Since the protein can act in trans, it is called the tram activator (tat). The tat gene product serves to turbocharge the replication of the AIDS retroviruses. Hence, in the short time that an infected lymphocyte may undergo cell division in response to a given antigenic stimulus, gut and its related proteins allow maximal production of the retrovirus and thereby increase the probability for successful virus infection of other lymphocytes. In general, the retrovirus of AIDS is a highly adapted pathogen. Its genetic functions subserve two essential prerequisites for any virus's survival, replica- tion and avoiding immune elimination. A full knowledge of the molecular mechanisms of viral replication and their relevance may be central to the control of the AIDS epidemic. 12 THE IMMUNOLOGY OF PEDIATRIC AIDS Arthur J. Ammann, MD. The pathogenesis of AIDS, felt to be a result of HIV infection, is best studied in infants and children, since they represent a more pristine host. Undoubtedly, HIV infection and its resultant clinical manifestations are a consequence of infection with this retrovirus as well as the interaction between HIV and other preexisting or subsequent infectious agents. Studies of infants suggest that HIV infection alone may result in impairment of the immune system and secondary susceptibility to opportunistic infection. Even in the case of isolated HIV infection, however, the clinical manifestations and severity of the disease may vary, implying that the time at which infection occurs (as early as 20 weeks gestation), the amount of viral inoculum, and preexisting immunodeficiency are important variables. Experimental evidence suggests that the monocyte/macmphage may be the initial cell infected with HIV and may subsequently be a major source of continued virus replication and infection. It is important to emphasize that certain organs have significant numbers of monocytes and macrophages that are CD4 receptor-positive (the CD4 receptor is required for HIV infection of cells). This may provide an explanation for the occurrence of the isolated brain and lung involvement some- times observed in infants with HIV infection. In vitro infection of monocytes with HIV may result in giant cell formation, with a histologic appearance similar to that of the giant cells found in tissue sections obtained from the lung and brain of HIV-infected patients. The interaction of HIV and other viruses may result in clinical features unique to either adult AIDS or pediatric AIDS. For example, Kaposi's sarcoma- a frequent malignancy in AIDS -has not been convincingly demonstrated in pedi- atric AIDS. On the other hand, chronic parotid swelling and pulmonary lymphoid interstitial pneumonitis (LIP) are frequently found in pediatric AIDS but rarely observed in adult AIDS. The pathogenesis of LIP was linked to infection with Epstein-Barr virus (EBV) in several studies which used EBV DNA probes to detect the presence of virus in lung tissue. The response to EBV infection in patients with AIDS is abnormal. In EBV-infected infants with AIDS followed prospectively, virus was cultured for several weeks prior to appearance of antibody to EBV antigen. There was an absence of an IgM anti-VCA response and failure to develop antibody to Epstein-Barr Nuclear Antigen (EBNA). IgG antibody to Anti-Viral Capsid Antigen (VCA) and antibody to Early Antigen (EA) remained high in most patients, suggesting persistent chronic EBV infection. This is in contrast to normal individuals where infection results in an initial increase in antibody to VCA, followed by a decline to low levels which persist for life. Patients with pediatric AIDS and EBV infection also have prolonged virocytemia, easily recoverable EBV, and increased numbers of EBV-infected cells. It is possible that the existence of HIV infection in the lung, followed by EBV infection, results in a lymphoid proliferative response manifested as LIP. EBV-infected B cells are more susceptible to HIV infection than uninfected B cells and may be stimulated by HIV antigens to excessive proliferation. A suggested interaction between HIV and EBV was based on observations in EBV- 13 infected adults who subsequently became infected with HIV and developed addi- tional immunologic abnormalities. The more common sequence of infection in pediatric AIDS, HIV followed by EBV infection, may result in a lympho- proliferative disorder. Adults have a reverse sequence more commonly, and they rarely develop LIP. The presence of LIP may modify the susceptibility of infants to opportunistic infection. Two studies note that patients with LIP had fewer opportunistic pulmonary infections and that patients with Pneumocystis carinii pneumonia (PCP) do not have evidence of pulmonary hyperplasia. HIV infection of immunocompetent cells may result in immunodeficiency by several mechanisms. Following infection, syncytia formation and fusion of cells occur with subsequent death in vitro. A similar mechanism in vivo could result in T-cell depletion. Cytotoxic T-cells may also destroy infected cells in vivo resulting in reduced numbers of T4 cells and the characteristic reversed T4/T8 ratios seen in most patients. However, early immunologic abnormalities occur prior to depletion of immunocompetent cells, suggesting that HIV infection may directly interfere with immune function. For example, HIV infection of T-cells in vitro results in decreased IL-2 and CD4 receptor mRNA and IL-2 and CD4 receptor expression. It is also known that Peripheral Blood Mononuclear Cells (PBMC) from patients with AIDS and preAIDS have decreased cytokine produc- tion in vitro. Many of these cytokines are essential for immune interaction, antiviral, and antitumor effects. Deficiencies of interferon-a (IFN-a), interferon-y (IFN-y), tumor necrosis factor-a (TNF-a), tumor necrosis factor B (TNF-B), interleukin-2 (IL-2), and interleukin-1 (IL-l) have been described. One or more cytokine deficiencies may result in secondary defects, such as abnormal monocyte/ macrophage function, decreased natural killer-cell activity, decreased antibody formation, and decreased T-cell immunity. Abnormalities of macrophage function may play a more critical role in the patho- genesis of HIV-induced immunodeficiency than previously appreciated. The macrophage may act both as a reservoir of HIV infection and, as a result of its central role in the T- and B-cell immunity, may play a primary role in early immunodeficiency . Immunodeficiency following HIV infection may also result from the immunosuppressive effects of HIV envelope glycoprotein or other immuno- suppressive regions of virus proteins. Following HIV infection, envelope glycoproteins are secreted to the surface of cells. Several regions of the envelope glycoprotein are capable of suppressing the immune response in vitro. Glycoprotein 120 (gpl20) is capable of binding to the CD4a region of the CD4 receptor and interferes with immune function in vitro as measured by mitogenic and antigenic stimulation. Prospective studies of patients with AIDS suggest that B-cell abnormalities may precede other laboratory features of immunodeficiency. Patients usually have polyclonal hypergammaglobulinemia. This may result from chronic HIV antigen stimulation or loss of suppressor T-cell regulation. In contrast, antibody levels to HIV antigens are not markedly elevated as is usually observed in other chronic viral infections. Further, specific IgM antibody to HIV is difficult to demonstrate in either acute or chronic infection. As the syndrome progresses, patients lose their ability to respond to other antigens following immunization. 14 Table 1. B-Ceil Abnmnalitics in AIDS * Polyclonal hypergammaglobulinemia W Failure to produce antibody following immunization w Increased spotttaneous IgG secretion, due to: 1) antigenic stimulation by HIV 2) increased numbers of EBV infected cells 3) HIV-induced T-cell dependent B-cell activation W Decreased B-cell response to antigens * Decreased B-cell response to T-41 independent mitogens T-cell abnormalities are numerous and profound. Early abnormalities consist of inability of PBMC to respond to antigens in vitro and of cytotoxic T-cells to kill target cells. In vivo, this correlates with absence of reaction to delayed hyper- sensitivity skin tests. As the syndrome progresses, PBMC from patients lose their ability to respond to mitogens and alloantigens and are unable to produce normal amounts of essential cytokines (IFN-a, IFN-y, TNF-a, TNF-b, IL-l, IL-2). The broad-based T-cell deficiencies are most likely a result of both intrinsic abnor- malities and severe T-cell depletion. Table 2. T-Cell Abnormalities in AlDS Number * Lymphopenia * Decreased T helper cells (decreased H/S ratio) * Decreased T suppressor cells m Increased Dr and OKTlO expression on CD8 cells Function * Absent delayed hypersensitivity shin tests * Diminished PBMC response to antigens * Diminished PBMC response to mitigens (PWM, Con A, PHA) * Decreased cytokine production IL-I, IL-2 IFN-a, IFN-y TNF-a, TNF-8 * Decreased Thymic hormones (thymulin) A number of monocyte defects have been reported in AIDS. Monocytes fail to mature at a normal rate, do not have normal chemotaxis and adherence, and, as determined by use of certain in vitro assays, are unable to kill some micro- organisms. An unanswered critical question is whether antigen processing or antigen presentation of HIV-infected macrophages is abnormal. The major abnormality of the complement pathway which has been described in AIDS is that of increased immune complex formation. This is probably a result of both non-specific polyclonal hypergammaglobulinemia and chronic antigenemia as a consequence of chronic infection with a number of microbial agents. Some of the severe consequences of chronic immune complex formation, such as renal failure, are rarely observed in patients with AIDS. However thrombocytopenia, which is more commonly found, may result from removal of immune complex coated platelets from the circulation. 15 Table 3. Complement Abnormalities in AIDS * Increased circulating immune complexes * Increased HIV specific immune complexes m Immune complex deposition (renal disease, thrombocytopenia) In order to establish a diagnosis of HIV infection, either antibody to HIV or the presence of HIV must be demonstrated. A number of tests for antibody are commercially available. Most of these are enzyme-linked immunosorbent assays (ELISA) and utilize HIV antigens coated on to plastic surfaces to detect IgG anti- body in the test serum. The assays are designed to be highly sensitive and there- fore readily detect antibody positives, but as a consequence also have a high rate of false positives. Table 4. Enzyme Linked Immunosorbent Assay (ELlSA) * ?????? 1) Disrupted virus placed in plastic wells or on plastic beads 2) Incubated with test serum 3) Antibody to antigen detected by enzymatic reaction. * ??????????????? 1) Sensitive - best for screening 2) High number of false positives (<50X are confirmed positive by Western blot) 3) A positive must be confvmed by Western blot It is necessary to confirm each positive by first repeating the ELISA and then, if again positive, confirming the presence of antibody to specific HIV antigens by a Western blot. Other antibody assays include indirect immunofluorescence and radioimmunoprecipitate assays and are primarily for investigational purposes. A major difficulty in the diagnosis of HIV infection in newborns and infants is the inability to differentiate between passively transferred maternal IgG anti- body to HIV and actively produced antibody from the infant. Unfortunately IgM antibody to HIV has been detected only inconsistently. There are several other methods of establishing HIV infection in the infant. Serial antibody testing by Western blot may demonstrate the emergence of new antibodies to HIV antigen. Culture of PBMC for virus or the use of DNA probes may demonstrate presence of HIV, but the methods are currently less sensitive than antibody assays. Newly developed assays for the detection of HIV antigen in serum may provide an alter- native means of testing. A diagnosis in pediatric AIDS can be confkmed using a few well established assays of immunologic function coupled with assays for virus infection or demon- stration of viral antigen. The confirmation of HIV infection is essential to provide appropriate care for infected infants and children. 16 TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN THE UNITED STATES Martha F. Rogers, M.D. The human immunodeficiency virus (HIV) is transmitted by three routes: 1) from mothers to infants during the perinatal period, 2) through parenteral exposure to infected body fluids, primarily blood, and 3) through sexual contact. Although other modes of transmission have been proposed, including transmis- sion through casual contact, through insect bites, through exposure to contami- nated needles used for tatooing, ear piercing, or acupuncture, and through receipt of hepatitis-B vaccine or immune globulin, there is little or no evidence supporting such occurrence. Perinutal Transmission Perinatal transmission accounts nationwide for about three-quarters of cases of HIV infection in prepubertal children. The epidemiologic characteristics of these children closely parallel those of heterosexual adults with AIDS, particu- larly women. Over half (65%) of reported cases of AIDS in women, 69% of heterosexual men with AIDS, and 73% of the perinatally acquired AIDS cases in children were related to IV drug abuse or sexual contact with IV drug abusers. The geographic areas most affected by heterosexual and perinatal transmission have been the New York City metropolitan area, northern New Jersey, and southern Florida. The majority of heterosexual men (74%), women (72%), and children with perinatally acquired infection (88 W) have been black or Hispanic. Most are inner-city dwellers of low socioeconomic status. Evidence suggests that perinatal transmission can occur by three modes: 1) transplacental passage of the virus in utero, 2) exposure to infected maternal blood and vaginal fluids during the labor and delivery of the infant, and 3) post partum ingestion of breast miIk containing the virus. The proportion of perinatrdly acquired cases attributable to each of these modes is unknown. Preliminary data from prospective studies of infected women and their infants indicate that the frequency of transmission from mothers to their infants may be as high as 50%. Both symptomatic and asymptomatic women can transmit HIV to their infants. The risk factors associated with transmission, however, have not been defined. Mothers can transmit HIV in more than one pregnancy. Each infected infant is at risk of developing AIDS. Table 1. Possible Risk Factors for Transmission of Hlvfiom Mothers to 7heir Infants Viral factors-viremia, latent vs. active infection, X cells infected Substance abuse or other environmental/behavioral factors Other infections present Level of immune suppression Continued exposure to HIV Host factors 17 These prospective studies also indicate that maternal HIV infection is probably not associated with adverse prenatal or neonatal infant outcomes, nor with an increase in obstetrical complications. Two studies have reported an increased frequency of spontaneous abortions among seropositive women, but three other studies have not observed this trend. To date none of the women in the CDC Classification-3 or less developed AIDS during the pregnancy. In one study, however, a trend towards an increased incidence of hospitalizations for infections in seropositive versus seronegative pregnant women was observed. In addition, a greater proportion of seropositive pregnant women developed complications during an average of 6 months' follow-up postpartum, compared with seropositive women who did not become pregnant and who were followed an average of 12 months. Parenteral Transmission Transmission through parenteral exposure to infective body fluids has occurred primarily in 2 populations: 1) in persons sharing contaminated needles used to inject illicit drugs, and 2) from donors to recipients of blood or blood products. Transmission through accidental injuries with contaminated needles or other cutting objects in the health care setting has been extremely rare, occurring in less than 1% of such injuries. About one-fifth of reported AIDS cases are attributable to transmission through use of contaminated needles for injecting illicit drugs. Seventy-four percent of these patients come from New York and New Jersey. Seroprevalence studies of IV drug abusers have shown infection rates of up to 70% in these areas, 42% in Boston, 11% in Chicago, and 10% in San Francisco. Several studies have shown that in IV drug abusers, seroprevalence is highest in those who are black or Hispanic. Transmission through receipt of infected blood or blood products accounts for 3 % of adult and 17 % of the pediatric AIDS patients nationwide. Cases are scattered throughout the United States with California and New York having the greatest number of cases. Most of the children with transfusion-acquired AIDS were trans- fused in the neonatal period or had coagulation disorders. No cases of transfusion-acquired AIDS have been reported in children trans- fused after initiation of donor screening for HIV antibody in March-April 1985. Although transmission through transfusion of seronegative blood can occur when the donor is in the early stages of HIV infection and is viremic but not yet producing antibody, this has been rare. In one study of the recipients of blood collected prior to HIV screening from donors who later developed AIDS, the risk of HIV infection following receipt of blood from an infected donor approached 100%. In instances of split donations, in which one recipient became infected, so did the other. Once a seropositive donor transmitted the virus to a recipient, all subsequent recipients of blood from that donor also became infected. Although donor screening procedures and heat treatment of coagulation products have markedly reduced the transmission of HIV through these routes, cases of AIDS in persons who received these products before these interventions will continue to occur. The incubation period for AIDS in adults with transfusion- acquired infection averages 3 years and has been as long as 7 years. The incubation is shorter for children, averaging 2 years and ranging up to 6 years. 18 Sexual Transmission Sexual contact is the most common mode of HIV transmission in adults, and accounts for over threequarters of reported cases. Sexual contact between homosexual or bisexual men has accounted for 95% of sexually acquired HIV infection, but heterosexual transmission is increasing, particularly in minority populations. In contrast to gay male cases, about three-quarters of women with AIDS and of heterosexual men with AIDS are black or Hispanic. The frequency of transmission between heterosexual sex partners is around lo%-15% in the partners of hemophiliac men and transfusion recipients, about 40% in the non-drug-abusing partners of IV drug abusers, and about 58 % in a study of partners of primarily IV drug abusers and Haitian immigrants. Some persons have acquired infection after only a few at-risk sexual encounters, while others did not acquire infection despite repeated contact over several years. Medical conditions (such as cervicitis or vaginitis), menstruation, and sexual prac- tices (anal intercourse) that involve greater exposure to blood and friable tissues increase the likelihood of transmission. Transmission has occurred, however, in persons engaging in vaginal intercourse exclusively and without any of the above conditions. Casual Contact Transmission through close but nonsexual contact (so called "casual") has been extremely rare. Only three possible cases have been reported. Two of these cases involved nursing care of bedridden patients associated with extensive and repeated contact with blood and body fluids of the infected patient. The other case involved apparent transmission between two siblings, but the nature of the contact was not well characterized. Nine other independent studies of over 400 family members of HIV-infected patients have not found evidence of household transmission. In addition, none of the family members of the over 30,000 AIDS cases reported to the Centers for Disease Control (CDC) has developed AIDS as a result of house- hold contact. Intervention methods designed to prevent further spread of HIV infection must consider the epidemiology of the infection including the modes of transmission, the characteristics of the currently affected populations, and the potential for spread within these populations and to other groups. 19 APPROACHES TO PREVENTION OF HIV INFECTION Walter R. Dowdle, Ph.D. The five basic mechanisms for prevention of infectious diseases include 1) immunoprophylaxis (vaccine), 2) chemoprophylaxis/therapy (drugs), 3) sanitation (environment), 4) lifestyle modification (behavior), and 5) vector control. Of these five mechanisms, the first four are applicable to prevention of HIV infection. There is no evidence to suggest that the AIDS virus is transmitted through insect or other vectors. The first two of the four mechanisms, vaccines and prophylactic/therapeutic drugs, are under development. Ideally, both will be incorporated into future strate- gies. Much progress has been made toward understanding the basic properties of potential retrovirus vaccines, but 5 to 10 years or more may be required before a vaccine can be realistically considered as a public health tool. How a vaccine will be utilized in prevention strategy will depend upon its availability, cost, efficacy, and safety. Greater promise has been shown for antiviral drugs, partic- ularly as we learn more about the pharmacology and clinical efficacy of certain classes of drugs. For the present, however, our strategy must rely on the two remaining mechanisms, modifying the environment and modifying personal behavior. Modifying the environment is of limited benefit, but some changes have already been accomplished. Tests for screening the blood of donors for HIV antibody have been used regularly for nearly two years. This screening has vastly reduced the risk of transfusion-associated infections. Donor screening and treatment of factor VIII has virtually eliminated the risk of AIDS for persons with hemophilia. The environment does not pose a major risk for health care workers. Needlestick injury would appear to be the greatest concern, but recommendations for caution by health care workers have been widely disseminated. Our main task has been to reassure the public that the general environment does not present a threat. The virus is not transmitted through casual social contact or food and water. The remaining and most important mechanism for prevention consists of modifying behavior. This is a difficult and often controversial task that in the past has not been considered effective for other sexually transmitted diseases (STDs) . Nevertheless, we must make a concerted effort to develop effective educa- tional programs regarding HIV infection. Specific mechanisms for modifying behavior include modification of sexual practices of infected persons, routinely offering testing and counseling to persons at high risk, treating IV drug abusers to preclude transmission of the virus through the use of contaminated needles, and information and education programs. There is considerable evidence that risk reduction already has occurred in the gay community. Effective information/education programs include a whole spectrum of activi- ties, ranging from TV spots to individual counseling sessions. An effective program requires multiple channels of information tailored to specific audiences and delivered through the auspices of a wide range of private and public organi- zations and institutions. The public Health Service Information/Education Program is directed to the general public, to school- and college-aged young persons, to other persons at increased risk, and to health workers. The program is budgeted 20 at over 79 million dollars, with 102 million proposed for next year. The general public can be informed and educated through hotlines, coalitions, ad campaigns, and clearinghouses. That, of course, forms the foundation and background on which more specific programs aimed at high-risk groups can be developed. Each of the nation's school systems will decide how best to implement education in AIDS prevention at appropriate ages. There is less argument here than may appear on the surface. Our interest is in assisting local school groups in developing their own curricula. We are trying to facilitate that activity, but by no means is the Federal government attempting to tell anyone what to teach. The individual school boards will make their own decisions. We do feel that there is great demand and eagerness in the schools to move on the education issue. Efforts at educating health workers can be productive, because they are a major channel of information to infected patients and in carrying preventive informa- tion to others. When we speak of educating those at increased risk for pediatric AIDS, the preferable strategy is to prevent infection in women of child-bearing age. This is a very difficult area. Those at increased risk are the female sex partners of men at high risk, intravenous drug users, prostitutes and clients. These are diffi- cult to reach. The second line of defense is to provide counseling to those already infected to help them enter into a program of comprehensive health care and follow-up, including avoidance of pregnancy. After that, our options grow less and less clear. In some geographic areas and for some populations, these information/educa- tion activities are beginning. To ensure maximum effectiveness, these programs must be constantly evaluated and modified if necessary. Increased knowledge and general awareness of prevention information is important, but our ultimate criterion of success must be a change in personal behavior that results in decreased trans- mission of infection. 21 NATURAL HISTORY OF HIV INFECTION IN CHILDREN Gwendolyn B. Scott, M.D. One hundred thirty-four cases of perinatal Human Immunodeficiency Virus (HIV) infection were identified in South Florida between January 1981 and December 1986. Each year since 1981, we've seen an increasing number of cases. In 1986 we identified one-third of our total case load, and so far in 1987 we are seeing at least one new case per week. These infants were born to 109 infected women. Drug abuse accounted for 22% of the disease in the mothers in compar- ison to 60% reported nationally. Fifty-one of these children meet the CDC surveil- lance criteria for AIDS; 81 others have clinical symptomatology and are diagnosed as ARC. Two, who are now 7 years old, are asymptomatic. Ninety-two percent of these children were black. The majority of children presented with clinical disease in the first two years of life (74%). There are, however, a number of children who present between the ages of 2 and 6 with the first manifestations of disease. The overall mortality in these children is 35 % , but among those who meet the criteria for AIDS, the mortality is 73.5 % . Pneumocystis carinii pneumonitis (PCP) and Candida esophagitis are the most common opportunistic infections. Failure to thrive is the presenting complaint. Lymphadenopathy , hepatosplenomegaly , and persistent oral thrush are some of the more common findings. We have seen disseminated cytomegalic virus infec- tion frequently, five cases of cryptosporidiosis, and one case of Mycobacterium avium-intracellulare. Tumors occur, but are rare in children. We have a few cases of Kaposi's sarcoma, one of lymphoma of the liver, and one of Burkitt's lymphoma of the lung. Opportunistic infections presenting in the first year of life are associated with a higher mortality. In an effort to better describe the clinical outcome of infection in pediatric cases, a syndrome approach has been applied. Table 1. Syndromes Associated with Pediarn'c HIV fnfecrion Wasting Syndrome Lymphoid Interstitial Pneumonitis Recurrent Bacterial Infection Encephalopathy Lymphadenopathy Syndrome Cardiomyopathy Hepatitis Renal Disease More than one of these syndromes may occur in the same patient separately or simultaneously. There appears to be a relationship between the immune response and the development of these syndromes. For example, patients with early onset pneumocystis pneumonitis or encephalopathy tend to have decreased evidence of immune response and have a higher mortality. In comparison, patients with LIP, lymphadenopathy syndrome, cardiomyopathy, recurrent bacterial infections, or renal disease generally have a lymphoproliferative response with hyper- 22 gammaglobuhnemia, lymphadenopathy, and hepatosplenomegaly. Children with PCP have an earlier age of onset and a higher mortality rate than those with LIP. Table 2. LIP and Early Onser PCP LIP PCP Mean Age of Onset 15.8 mos. 6.2 mos. Median Age of Onset 13.5 mos. 5 mos. Overall Mortality 25.7% 85.7% The overall mortality for PCP is 85.7 % as compared to 25.7 % in the LIP group. The immune response in these groups differs. PCP is associated with a lympho- ablative response, while LIP is associated with a lymphoproliferative response. A greater understanding of the spectrum of disease and knowledge of the natural history of the various syndromes wiIl allow better predictions of prognosis. Although not all HIV infected children die early in life, this is an illness that is unpredictable and is associated with a high rate of morbidity and mortality. The child is usually the first member of the family that is identified as being infected. In this situation, screening of the parents and siblings is indicated. In the majority of cases, the mother is asymptomatic at the time of diagnosis of HIV infection in her infant. Of the 109 mothers in our patient population, 30% have subsequently developed AIDS or ARC. Seventeen mothers have died. This series of patients has offered us the opportunity to evaluate the risk of an HIV infected pregnant woman delivering an infected infant. Twenty-three HIV infected women have had 40 subsequent infants after the birth of the index case. Not every subsequent infant will be infected. We have followed one woman who has delivered four infected infants, but another mother had an infected infant and subsequently delivered three uninfected children. Still another had an infected infant, an uninfected one, and then another infected one. We obviously do not know what factors cause a mother to pass the infection on to her infant. Of all the subsequent infants, 52% are infected. This represents a substantial risk for these women and emphasizes the importance of identifying them so they can receive appropriate counselling regarding pregnancy. This population may repre- sent a special population of women, and further studies are underway to deter- mine the risk of having an infected child in an HIV-positive woman who has not had previously infected infants. In conclusion, pediatric HIV infection presents with a broad spectrum of disease and is associated with a high mortality rate. The majority of children with this disease are black or Hispanic and reside in the lower socioeconomic areas of the inner city. It is important to recognize infected children early so that appropriate instructions for care can be given to the parent and regular medical followup can be instituted. In addition, with the development of anti-viral drugs, early diag- nosis and recognition will be imperative, so that early treatment can be given. Screening of the family is important to identify infected family members and to give appropriate counselling and education. The HIV-positive woman is at risk for giving birth to an infected infant. Prevention of perinatal infection will only be accomplished by prevention of disease in women or by other interventions, such as drug therapy. Identification of HIV-positive women is important so that appropriate education and counselling can be provided. 23 NATURAL HISTORY OF HIV INFECTION II James Oleske, M.D Estimates from the CDC suggest that by 1991 there will be 12.5 million Americans infected with the AIDS virus (Human Immunodeficiency Virus-HIV) and 250,000 of these will be symptomatic AIDS cases. Based on our experience and those of others caring for pediatric AIDS cases, by 1991 there may be 10,000 to 20,000 symptomatic HIV infected infants and children in the USA. Our difficulties in providing care to over 60 active pediatric AIDS cases at Children's Hospital of New Jersey in Newark indicate major problems in the near future. The health care requirements of infants and children infected with HIV are extensive and include the complex tertiary medical capabilities of a pediatric hospital and intense psychological services. The care we provide to these chtidren includes vigorous nutritional support, including placement when necessary of intravenous catheters, early hospitalization for treatment of possible infection episodes, and monthly replacement therapy with intravenous gamma globulin. Tissue biopsy of lung, lymph nodes, thymus and bone marrow, as well as CAT scan, gallium scan and esophagoscopy are frequent requirements in the clinical evaluation of these children. Research and time consuming investigational drug studies are now being undertaken on our patients. All of these activities -diagnosis, clinical care, and necessary research- have placed an enormous burden on the available resources at our children's hospital. Besides the medical dilemma posed by AIDS, there is the significant public misunderstanding of this disease with ongoing stigmatization of patients and their families. The development of antibody screening tests has substantially reduced (although not eliminated) the risk of blood transfusion acquired AIDS. It is true that the majority of cases of AIDS in children is due to perinatal exposure from an infected mother, but for the next five to six years we must follow a cohort of newborns who received small blood transfusions in the nursery between 1980 and 1985, and who are at risk of developing this disease. As pediatricians we must insist that we have safe blood products for use in children and that we use blood products appropriately. It doesn't take a sophisticated laboratory to make a diagnosis of AIDS. If the epidemiology and the clinical historic patterns are present, we are comfortable in Newark making the diagnosis after simple laboratory studies including: Complete Blood Count (CBC), quantitative immunoglobulin assays, liver func- tion testing, chest X-rays, and HIV antibody testing. Anemia leads the list of abnormalities. These children are almost all anemic and most have elevated liver enzymes. Table 1. Laboratory Findings in Infants and Children Hypergammaglobulinemiia/Hypogammaglobulinemia Anemia Depresssed T-helper cells Lzukopenia Reversed lymphocyte subset ratio Thrombocytopenia Depressed lymphocyte responses to mitogens Elevated level of circulating immune complexes Decreased specific antibody responses Elevated serum transaminase levels The clinical spectrum of illness in children with HIV infection is expanding as our experience with this disease increases. When we looked carefully at our 24 AIDS and ARC children with failure to thrive, we realized that many of these infants had problems with the central nervous system. Many had a chronic encephalopathy. Others had primary HIV infections of the CNS, with failure to thrive and loss of developmental milestones, the equivalent of the dementia seen in adults. A child who is otherwise well can present with p&nary CNS infection without any other manifestation of AIDS, and even an essentially normal immune system. Table 2. Neurologic Findings in Children with HIV Infection Developmental Delay/Loss of Developmental Motor Dysfunction Milestones Microcephaly Chronic Encephalopathy Abnormal CT Scan Findings-Cortical Seizure Disorders Atrophy, Calcifications One of the clinical problems we have had is dealing with the gastrointestinal manifestations. These children have a variety of GI problems including disten- sion, diarrhea, inability to eat, and tremendous discomfort. The resultant effect is marked malnutrition. In seven of fifteen autopsies, we saw cardiovascular abnor- malities. Three were congestive cardiomyopathies and four arteriopathies. One case resulted in a fatal coronary artery aneurysm. Unlike adults, infants with HIV infection will most likely be symptomatic over the course of their illness. There are some differences between pediatric and adult AIDS, and these are outlined in the following table. Table 3. Differences between Pediatric and Adult AIDS 1. Kaposi's sarcoma and B cell lymphoma are rare in children 2. Hepatitis B infection is less frequent than in adults 3. Hypergammaglobulinemia is more pronounced in children 4. Peripheral lymphopenia is uncommon in children 5. Lymphoid interstitial pneumonitis (LIP) is much more common in children 6. Some children will have normal ratio of helper to suppressor T cells (although quantita- tively T helper cells are diminished) 7. Serious bacterial sepsis is a major problem in children 8. Dysmorphic features may be found in some children 9. Acute mononucleosis-like presentation is rare in children 10. Progressive neurologic disease secondary to primary HIV CNS infection is more pronounced in children The final mortality rate is unknown, but with our present program at Children's Hospital, we have seen the mortality rate decrease to 35%. With the use of intravenous gamma globulin therapy, the quality of life for our patients has improved, with recurrent septic episodes decreasing from 45% in 1983 to 5% in 1986. We try to provide optimum care to each child, comprehensive rehabili- tation services, early intervention programs, and psychological support for the families of our patients. We have learned that HIV probably causes primary infec- tions not only of the immune system, but also of the CNS, heart, kidneys, and liver. This primary multisystem/organ infection with the HIV virus as well as its known secondary opportunistic infections and malignancies present a major problem in devising therapeutic programs. Educational programs regarding the real risk of transmission, i.e., blood contaminated needles used in drug addic- tion, and sexual contact, need to be extended to school age children and hard-to- reach risk populations. If child-bearing age women at high risk for HIV infection would avoid pregnancy, we eventually would see no new cases of pediatric AIDS. 25 HIV TRANSMITTED BY BLOOD PRODUCTS Margaret W. Hilganner, M.D The extent to which the national blood supply has been contaminated by the Human Immunodeficiency Virus is unknown. With a basis of epidemiologic data, however, one can say that the virus probably came into the blood supply in 1977. Retrospective study of stored samples of hemophiliac plasma showed the appear- ance of anti-HIV antibodies in 1979 in a few patients (i.e., became seropositive) and in the majority of hemophiliacs during the years 1980-1983. The first hemophiliac was reported with the disease in 1981. When widespread testing of the donor population became available in March 1985, 0.4%-0.9% of donors were found seropositive nationwide, with the highest figures in those cities (New York, Miami, Los Angeles, and San Francisco) with the greatest reported number of AIDS patients. Incidence The CDC has recorded a total of 939 cases of AIDS related to transfusions of HIV-contaminated blood products as of 2 March 1987. This figure is 2.9% of the total persons reported with AIDS and includes all adults, adolescents, and children. Of this total, 287 individuals have had hemophilia or other coagulation disorders and have been transfused with fresh frozen plasma, cryoprecipitates for factor concentrate, while 652 individuals have been transfused with red blood cells or components of blood. When the figures for the children are separated from the total, we find that 78 children or 18% of the total 453 children reported with AIDS have had the virus transmitted via blood and blood products. Of those, 24 (5%) have had hemophilia and 54 (or 12 W) have been transfused for other reasons. Although these numbers are increasing with time, the percentages of the total have remained stable. The higher percentage in babies transfused with blood or components is probably related to the shorter incubation period seen in infants, while the percentage in young hemophiliacs is only slightly higher than the figures seen in the adult hemophiliac. Natural History Information about the natural history of the disease in the transfused patient is evolving slowly, but with some accuracy, because the date of transmission of the infected blood can be ascertained in many cases. A wide spectrum of disease seems to exist, with variables related to age, underlying diseases for which the transfusion was given, and the product used for transfusion. The Red Cross "Look Back" study currently going on in all Blood Banks is tracing recipients of blood from donors known to have been HIV-negative on subsequent testing. The Transfusion Safety Study (TSS) is enrolling all donors and recipients of HIV-positive blood donated in the six months prior to universal screening of all donors for seropositivity in four high risk cities in the United States. With these two studies, one hopes that complete epidemiological information will be obtained concerning the natural history of AIDS as transmitted through blood products. At present, data from the TSS show that 90% of those patients who received a 26 unit of blood found retrospectively to be HIV seropositive have themselves become seropositive. Although 75% of recipients died within one year after the trans- fusion of causes not related to AIDS, there is a potential reservoir of unsuspecting anti-HIV positive individuals deserving close follow-up and counseling. Children tranfused in the newborn period who subsequently developed AIDS were first reported in 1983 by Ammann et al., who found that symptoms appeared six months to three years post transfusion. Others have shown that the incubation period from transfusion to the appearance of symptoms seems shorter in those children who were transfused as very small premature babies, when compared to the older child where the incubation period may be the same as in the trans- fused adult. In the adult, Cm-ran has shown that the incubation period may be 15 months to 57 months (mean 27 months), and current CDC data suggest a span of seven years. In addition, Cm-ran showed that blood components other than those used by hemophiliacs could transmit AIDS. The product used for transfusion has marked influence on the transmission of disease. Those products containing white cells appear to have transmitted disease more readily than red cell products. For example a set of twins seen at The New York Hospital were transfused with components from the same donor. The twin receiving the red cells did not become HIV positive, while the twin receiving the platelets developed signs and symptoms of AIDS within 16 months. Those who received a greater number of transfusions in the period 1980-1985 are more likely to be seropositive than those receiving a smaller number of trans- fusions or single donor units. For example: only 12% of the 84 transfusion- dependent thalassemia patients at The New York Hospital-Cornell Medical Center in New York City are seropositive. The figures for hemophiliacs, however, are as follows: Table 1. HIV Starus of Hemophiliacs-NYHXUMC Total Anti-HIV Positive 119/163 Adults 2 18 years 83194 Children < 13 years 19143 < 18 years 36169 73% 88% 44% 52% The thalassemia patients have a donor exposure of 12-24 per year, while the hemophiliac may have a donor exposure of 800,000 to 1 million per year. The single donor unit is less likely to be contaminated than the pooled donor product from which the factor concentrates for the hemophiliac are manufactured. The hemophilia patient population, however, appears to be different from the homosexual or IV-drug-using population in relation to progression of HIV disease and infectivity of sexual partners. For example: only 20%-30% of the seropositive hemophiliacs have the syndrome of AIDS related complex (ARC), and only 2% have developed symptoms of AIDS. This figure appears substantially lower than for the homosexual population, where 30%-35% of those followed longitudi- nally have developed AIDS. Measures Taken to Prevent Transmission of HIV in Blood Products: Although HIV transmission via blood transfusions was recognized before a test was available to define the HIV antibody status, decisive measures could not be designed to insure the purity of the national blood supply. In the spring of 1984, the New York Blood Center developed a confidential intake questionnaire allowing 27 the center to determine whether the donor was at risk and thereby to designate whether the blood donation should be used for transfusion or discarded. This process of self-exclusion allowed the donor to preserve his confidentiality and contribute to improving the quality of the blood supply. Self-exclusion has now been adopted by all other blood collection agencies. Table 2. Measures Taken to Prevent Transmission of HIV in Blood and Blood Producrs 1. Self-elimination of at risk donors 2. Screening of Donor-March 1985 HIV antibody testing (ELISA) 3. Treatment of pooled products: Heat-wet or dry state Solvent/Detergent B-Propriolactone, U-V Light Monoclonal antibody derived Recombinant DNA derived 4. HIV-Antigen tests Treatment of the pooled plasma concentrates of clotting factors was begun in 1984 to decrease the amount of hepatitis virus contamination. Subsequently all of the methods used were found effective in the elimination of HIV: Beta propriolactone , ultra-violet light, solvent-detergent treatment, and heat have been used to treat the concentrates in the wet or dried state. The Dry Heat method is the current choice. Monoclonal antibody separation and recombinant manufac- ture of factors are being tested and appear promising. In 1985 the ELISA screening tests were introduced to identify blood or plasmaphoresis products containing HIV-positive antibodies. These tests are 99.2% specific for antibody and 93.4 %-99.6 % sensitive. The Western blot test performed on all positive donations is 75 % sensitive for HIV antibodies. Newer ELISA tests currently being tested are even more specific than those in use. With all of these tests, the blood supply has been rendered virtually free of donations contami- nated with HIV.' The problem remains for the donation given in that period between infection and development of antibody. A few recipients of red blood cells from units which tested seronegative at time of donation have become antibody positive: the blood donor has also subsequently become antibody positive. Many more are being iden- tified with the "Look Back" program. We look forward therefore to the licensure and marketing of a test for HIV antigen which will close the time span between infection and antibody development, so that we may have a national blood supply completely free of HIV. 28 SUPPORTIVE CARE AND TREATMENT OF PEDIATRIC AIDS Arye Rubinstein, M.D. This summary addresses some specific issues which may alter the course of the disease. Supportive Care Failure to thrive due to a variety of etiologies is one of the major features of pediatric AIDS. In some cases, malabsorption and protein-losing enteropathy are identified. In others, it may be related to factors such as chronic infection. Proper nutritional support (adequate caloric and protein intake) in many instances may be crucial for the care of the child with AIDS. Where this goal cannot be achieved by oral feedings, one has to consider nasogastric feeding or intravenous hyper- alimentation. In our experience nasogastric feeding is of limited value. Gener- ally, weight gain could be achieved through intravenous hyperalimentation using venous (broviac) access, but this may be compromised by the development of infections in the access lines. Infection Control and Prophylaxis Probably the most frequent problems in children with HIV infection, especially under the age of 2 years, are recurrent bacterial infections which may progress to sepsis and meningitis. The optimal strategies to prevent these infections have not yet been established: I) Antibiotics (trimethoprim-sulfa, ampicillin). Several groups have suggested that the use of prophylactic antibiotics may avert the cata- strophic outcome of acute infections, especially in those patients who have a severe underlying B cell deficiency. The drawbacks for the use of prophylactic antibiotics are the development of side effects, resistant bacterial strains, and poor compli- ance. II) Intravenous gamma globulin. Intravenous gamma globulin has been applied in pediatric AIDS since 198 1. The rationale for the use of this therapy was the documentation of an underlying B cell defect. In our experience this approach has significantly reduced bacterial infections, especially in the younger age group. Many unresolved issues exist with regard to this treatment: 1) what dose is to be used; 2) is the higher dose currently used by us (300mg/kg) advanta- geous over the low dose used in some agammaglobulinemic patients (lOO-2tig/kg) with regard to a) the delay of immunological attrition, b) preven- tion of infections, and c) removal of circulating immune complexes; 3) although no risks have been involved with intravenous gamma globulin, it is a costly treat- ment and requires a twice monthly 2-3 hour hospital short-stay admission; 4) should the European double-blind control study on IV gamma globulin be dupli- cated in the U.S. ; and 5) should gamma globulin be used in any HIV infected child who has a B-cell defect or should it be restricted to those who present clini- cally with infections. Treatment of Specific Infections Certain infections in AIDS are extremely difficult to manage. Our experience demonstrates that salmonellosis is extremely hard to eradicate. Trimethoprim-sulfa, ampicillin, or ceftriaxone have failed in many cases to elim- 29 inate the carrier state. While in imrnunocompetent hosts the carrier state is of no risk, children with AIDS who are carriers of salmonella often suffer recurrent septic episodes. New strategies should be designed, therefore, to treat this condi- tion. One of the promising medications is Fluroquinolone used at 4OOmg twice a day. Pneumoqstis cariniipneumonia (PCP). The most frequently utilized treatment includes trimethoprim-sulfamethoxazol. In cases of failure, pentamidine is introduced. Other medications such as dapsone in combination with other treat- ments or as an alternate treatment have not shown great promise. Disseminated cytomegalovirus (CMV} infection with/without retinitis. No treat- ment has achieved permanent improvement. Trisodium phosphonoformate (Foscarnet) may have a role. Variceffa. A benign disease in immunocompetent children, varicella may be life-threatening for immunocompromised patients. Children with apparently normal in vitro lymphocyte mitogenic responses to specific and non-specific mitogens and with normal T4 cell numbers and percentages have developed fatal varicella. We, therefore, have adopted the policy of administering acyclovir in any case where an extensive vesiculation occurs or where new vesicles develop after the fourth day of the disease. Treatment Modalities for the Direct or Indirect Control of HIV Infection 1) Immuno-reconstitution or immuno-potentiation. A whole host of such modal- ities has been attempted in adults, including: bone-marrow transplantation, thymic transplantation, thymic hormones, alpha and beta interferon, interleukin-2, intravenous gamma globulin, isoprinosine, imuthiol, and enkephalins. The results have been disappointing. They do not appear to control the virus, and some of these immunopotentiating agents may activate virus replication. Experience with these agents in children is limited. Several thymic transplants have been performed but did not result in permanent objective benefit. The use of thymic transplants and thymic hormones in children is of special interest, since children with HIV infection demonstrate early in the disease course low levels of thymulin (FTS). Our trials with thymic hormone- fraction V-have not yielded encouraging results. Thymic hormones seem to temporarily improve T cell functions, but subsequently a phase of rapid immunological attrition and disappearance of T4 cells was detected. 2) Antiviral agents. A number of antiviral agents have been used in adults. These include reverse transcriptase inhibitors such as ansamycin, suramin, Foscamet, AZT, dCT, AL-721, a lipid component that promotes the extraction of cholesterol from the viral membrane, and ribavirin (Virazole) which inhibits guanyl transferase in the capping of the 5' end of HIV mRNA. Currently the two most promising drugs are AZT and dCT. Phase I trials with AZT in children with AIDS are in progress. In adults it has major side effects. dCT seems to have less side effects in adults, but has the disadvantage of limited penetration of the blood-brain barrier. The frequent and devastating CNS disease in children with HIV infection has to be taken into consideration when an antiviral agent is selected. Infection of fetal brain could be documented in the first trimester of pregnancy. Brain atrophy can also be documented in neonates by CT scans. Consequently, early treatment of CNS disease is imperative. Any antiviral drug that does not penetrate the blood-brain barrier, therefore, may be of little benefit for the treat- ment of HIV infection in the pediatric age group. 30 3) Hyperimmune Serum. We have used hyperimmune serum intravenously since May 1984. Its benefit for the control of HIV infection has not yet been established. Hyperimmune serum, however, may have a major role in the preven- tion of infection. It should be considered for use in HIV-infected women during early pregnancy to prevent fetal infection. 4) Combination treatments. Two forms of combination treatments are to be considered: a) the combination of various antiviral agents. Some in vitro studies suggest, however, that the combination of two or more antiviral agents may result in antagonism. For example, in vitro AZT and ribavirin seem to antagonize each other's effect on the AIDS virus; and b) the combination of antiviral agents and immunopotentiation. Antiviral agents may avert the activation of HIV by immunopotentiating agents. 31 INTRAVENOUS DRUG ABUSE AND WOMEN'S MEDICAL ISSUES Constance B. Wofsy, M.D. Epidemiology Women constitute 7% of all reported AIDS cases in the United States, in striking contrast to the ratios elsewhere. Of women with AIDS, 28% are white, 51% are black, 20% are HispanicLatino. Table 1. Women with AIDS Percent of Total AIDS Cases International Central Africa 40%-50X Haiti 20X-25% Canada, France 12% u.s.* 1% *If male homosexuals/bisexuals and hemophiliacs are excluded. women make up 30% Fifty-two percent of women with AIDS are intravenous drug users (TVDUs), but 27 % are non-IVDUs who were infected by a male sexual partner, usually an IVDU male. Of importance, 78% of women with AIDS are between the ages of 13 and 39, the peak childbearing ages. In pediatric AIDS, 45% of white and 88% of non- white children acquired the disease from an IVDU parent. It is estimated that there are more than a half million regular or casual IVDU women in the United States. As many as 75,000 women IVDUs and 20,000 non- IVDU female partners of male IVDUs may already be infected with the virus. With an estimated l-2 million Americans infected, there may be 200,000 women who carry the virus. Many haven't a clue that they are infected. The most highly represented populations of infected women, IVDUs and nonwhites, ate already highly stigmatized, but we must not let fear of stigma immobilize educational efforts. Tmnsmission HIV has been isolated from blood, semen, and cervical secretions. Transmission can occur by vaginal intercourse from man to woman and from woman to man. Iong-term sexual partners having unprotected sex with an infected person for several years have a 15 % -45 % chance of becoming infected. An interesting study done in Miami examined the percent of seroconversion in 32 couples after they learned that one was seropositive. Eight chose abstinence and none seroconverted. Ten chose to use condoms and only one seroconverted. Fourteen did nothing in the way of protection and 12 became seropositive. `able 2. Reintionship Betwen Condom Use and Seroconwrsion N SEROCONV - Abstinence 8 0 Condom lo I No Condom 14 I2 FischL et al. JAMA 1981; 257640. % - 0 10 86 Sexual partners who also share needles are at even greater risk. 32 Women Who Use IV Drugs IVDUs are hard to reach. Only an estimated 15% are in treatment programs. To reach others, we must rely on community networks, health clinics, jails, schools, churches, and the media. For those with little education and short atten- tion span, the message must be simple and direct, and the language culturally specific. Many who use drugs do not perceive of themselves as users. Those who do not understand the health risks and the need to clean needles may continue to share because they erroneously consider their partner to be nonrisk. Sharing is socially expected; the urgency of the fix exceeds the risk; carrying drug paraphernalia like a clean needle or bleach bottle may make one subject to arrest. The sexual and needle risks for the woman often come from a man who is also a user, and even more recalcitrant in acknowledging his own risk and in taking responsibility for his female partner. Our research group in San Francisco studied 289 sexually active women, none of them prostitutes, and found that 5% were seropositive. These were self-referred, so they do not represent a cross-section of the city. All of the seropositives have a personal history of intravenous drug use or have a sustained relationship with a specific high-risk partner. For over a year and a half, we followed 200 women with no such personal history and found only one seroconversion in a city rampant with HIV. Women IVDUs have few resources. They often have responsibility for children, multiple health problems, lack of family support, lack of money, depression, and low self-esteem. Prostitution may be a means of support for the drug habit and family. HIV infection und Pregnancy IV drug use does not inhibit fertility; some of these women have several children arid may desire more. Birth control is often limited because of perceived lack of risk of pregnancy, irregular periods, decreased sexual frequency as a result of drug use, and lack of power to control the sexual expectations and preferences of male partners. Few programs are targeted at pregnant addicts. Existing programs may be costly and too understaffed to deal with family patterns of abusive treatment, implemen- tation of childbearing skills, and birth control education. An infected woman has a 20%-60% chance of passing infection to her child. An infected child is very likely to die, or be severely ill by two years of age. Pregnancy may accelerate HIV expression in the woman and thus should be avoided for the sake of mother and child. In one study, however, it was found that 25% of infected babies were born to mothers who hadn't a clue they were infected or that their partners were in a risk group. The infected infant estab- lished the mother's diagnosis. Many women who have had an infected child nevertheless have proceeded to have additional children despite intensive culturally specific counseling. Child- birth may provide self-esteem or be culturally expected. Chnical Expression of HIV Infection in Women The spectrum of HIV-related infections and malignancies is similar in men and women, except that women rarely get Kaposi's sarcoma. Gynecologic problems do not seem to be significantly increased. Symptoms of HIV infection in women may be overlooked by physicians for 33 many reasons. Non-IVDU women are perceived to be a low risk group and HIV symptoms are nonspecific. IV drug users have medical problems whose symptoms mimic HIV related disorders (e.g., bacterial endocarditis, cotton lung, skin infec- tions). Physicians may feel inadequate to the task of AIDS care, may wrongly assume that all infected women are IV drug users or prostitutes, or may not have overcome their own fears. It is known that strong stigma and profound repercus- sions may result from the identification of an infected individual. Availability for HIV testing or adequacy of the medical staff and community to deal with the consequences are lacking. Thus, strong clues to infection may be overlooked and women may proceed under the illusion that there are no risks. Societal Issues for Women Infected with HIV HIV infected women come from all walks of life. Forty-eight percent don't use IV drugs. Many issues cross all class, race, and cultural boundaries-for example: 1) extreme isolation-infection is often kept rigorously secret. depriving women of the desperately needed support of family, friends, community, and particularly other infected women; 2) profound grief for the loss of health, body image, sexuality, and childbearing potential; 3) unavailability of medical care, counseling, child care, housing, and related services; 4) lack of informed primary care, OB/GYN, sex counselors, and abortion counselors; 5) the burden of making decisions about initiation, continuation, and termination of pregnancy: 6) the lack of natural "community," such as shared by gay men; 7) the abruptness of the diag- nosis, which may be disclosed at the birth of an infected baby or death of a spouse; 8) loss of self-esteem-feeling dirty, useless, unwanted, and unlovable; 9) the feeling of responsibility from watching a child die; 10) the stigma that "women with AIDS are prostitutes who infect their children"; and 11) lack of male respon- sibility, and the societal assumption that women have the responsibility for control of sex and conception. Importance of all Women to the AIDS Epidemic Women still constitute the large bulk of the country's educators and caregivers through roles of teachers, nurses, social workers, counselors, girlfriends, wives, and mothers. All persons in these positions shoulder a great responsibility. They are expected to overcome their own fears, become comfortable with sexual, drug, and lifestyle issues, acquire wisdom, nurture and teach the young, comfort the fearful, and care for the sick. It's a tall order. 34 EDUCATION TO PREVENT HIV INFECTION Karolynn Siegel, Ph.D. Education regarding modes of transmission of HIV infection remains the most important public health strategy for controlling the spread of AIDS. Education must mean more than just imparting information about practices that place one at risk of becoming infected or of infecting others. It must also aim: to motivate or persuade people to adopt certain behaviors and relinquish others, to eliminate irrational fears about transmission through casual contact, to debunk myths and stereotypes about the "kind of people" who get sexually transmitted diseases, to dispute notions of culpability or blame for the epidemic, to instruct all levels of society in safe sexual practices, and to insure cooperation in anti-drug programs. While there is widespread agreement on the central role that education must play in stemming the epidemic, there is somewhat less agreement on who should be educated and at what ages, what messages should be communicated, and who should assume responsibility for this education. These issues are currently the focus of much public discussion and debate. I want to emphasize the need to create a collective sense of national purpose in combatting this disease. AIDS is still viewed by the majority of people as the problem of a few select and socially isolated groups. We must strive to over- come a "we/they" mentality. We must promote a feeling that as a society we all have a shared interest in controlling this epidemic, which must take precedence over more narrow self or special group interests. Everyone needs to feel a personal investment in bringing about a solution to the problems the epidemic has posed. The establishment of a national office of AIDS education, or a national director of AIDS education, as recommended in the Institute of Medicine report, would constitute a very important first step. The public must receive a clear and unequivocal message that this problem merits a national plan of action and concerns all Americans. In England, Prime Minister Thatcher recently distributed a flyer under her name to every household in the country, informing people of the seriousness of the AIDS problem and telling them what they could do to protect themselves. This action sends a clear and powerful message to the populace. It says that this matter has the attention of the highest leaders of the country; every citizen should be informed about it and concerned with helping control it. I would like to move on to the question of "who should be educated?" Clearly, we must continue to focus heavily on the established risk groups-gay and bisexual men and intravenous drug users and their partners. We must target extensive educational activities to blacks and Hispanics, groups greatly over-represented among those with AIDS. We must enlist ongoing cooper- ation of support groups, community leaders and community-based organizations and must always consider cultural norms. We must find a way to tie the hoped- for behavior change into their own value and belief system. The importance of bearing a healthy child may be used to help perspade women to use condoms as protection against AIDS and other sexually transmitted diseases (STDs). 35 We know that adolescence is a time of experimentation that often involves drug use and sexual experimentation. The AIDS epidemic has increased the urgency to reach a goal of having "every junior and senior high school student receive timely STD education." A principal concern is how we should communicate. Here, we can draw some lessons from our efforts over the past few years to educate risk groups members - especially gay men. Our own research indicates that some of the messages contained in risk-reduction guidelines, which have been used as a principal educa- tional tool among gay men, have sometimes had unintended negative conse- quences. Recommendations like `know your partner" and "reduce your number of partners" have often created a false sense of security. One can rarely take the kind of exhaustive sexual history from a prospective partner that would be neces- sary even to begin to evaluate the degree of risk inherent in sexual encounter. We have found that men who continue to engage in risky sex, but with fewer partners or nonanonymous partners, believe that they have adequately reduced their risk of infection because they are in compliance with safe-sexual-practices guidelines. Similar messages are being used now in educational materials directed to the heterosexual public. While multiple messages about different prophylactic behaviors may not seem to be competing with each other, they are. The message we communicate should be unambiguous, confrontational, and consistent. There are only two acceptable adaptations to the threat of the infection-abstinence, or using a condom in every sexual encounter where a risk of transmission may exist. If you offer people several alternative ways to adapt, they wilI usually choose the course of action that involves least personal change. There would be no problem if the alternatives were all equally efficacious, but they rarely are. Who should do the educating? The source of any message is an important deter- minant of the attention it will receive. Therefore, I would recommend that we make greater use of opinion leaders in trying to alter the public's attitudes toward the epidemic and modify sexual norms among sexually active individuals. Opinion leaders are widely esteemed public figures who have the confidence and trust of much of the public. Because they are respected and trusted, their positions on matters are sought and afforded a special consideration. They can perform an especially valuable role in shaping public attitudes around such controversial issues as AIDS. There is the need to develop strategies for changing social attitudes and norms to support the adoption of behavior that will slow or halt the spread of infection. Social norms can be a powerful force in constraining certain practices. The need for the acceptance and approval of others is an important motive in shaping behavior. Peer social pressure is the most compelling force for modification of life style of adolescents in particular. Sex has always been considered a private act. Now, however, we are compelled to recognize that it can sometimes have public consequences. We can no longer afford to assert the position that what someone else does sexually is solely his own business. We must acknowledge that we have a vested interest in employing positive social sanctions to encourage people to conduct themselves in a way that will contribute to the control of the epidemic. We have to create a social environ- ment in which abstinence is a positively sanctioned option. For those individuals who choose to engage in intimate sexual relations, we must confer social approval 36 on those who behave in a sexually responsible way. People must come to regard the use of condoms as a normative expectation. At this time, we must depend on the schools to educate children about AIDS, STDs, and drug use. To pretend that we can rely on parents is really to abrogate our responsibility and to know this may leave many children unprepared to protect themselves against these threats. There are no easy answers to the problem of educating the public about AIDS. While there is some base of knowledge and experience to guide us, the diffrcul- ties that confront us are formidable. For example, the popular perception that AIDS remains a "medical mystery" and that there is disagreement even among the supposed experts on some matters greatly complicates the educational task. When available scientific evidence is regarded as indeterminant or provisional, its power to influence behavior is likely to be significantly diminished. 31 LEGAL ISSUES SURROUNDING MEDICAL CARE, TREATMENT, AND RESEARCH OF CHILDREN Harold Ginzburg, M.D., J.D., M.P.H. Introduction The ethical and legal issues surrounding informed consent and the individual right of privacy in the care and treatment of minors and in their participation in research protocols thus far are not unique to those infected with HIV. We can apply precedents derived from previous decisions. These form a base from which to build ethical and legal criteria to manage issues created by the AIDS epidemic, some of which may now be unforeseeable. The Right to Knowledge: Informed Consent Informed consent is a merger of the sharing of knowledge and the receipt of permission to proceed with the therapeutic or research intervention; informed consent is educated consent. Obtaining such consent from a competent adult is significantly different from obtaining consent for a minor or incompetent adult. A clinician or clinical investigator should seek informed consent only under circumstances that provide the prospective patient or research subject or their respective legal representatives with sufficient opportunity to consider whether or not to participate in the treatment or research. The decision-making process should be free of the possibility of coercion or undue influence. The information provided by the health care professional must be in language that the patient or research subject can be expected to understand. No informed consent, either oral or written, may include any exculpatory language through which the subject or representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability or negligence. Informed consent has become a structured and formal process; a written docu- ment is prepared by the medical institution which explains the proposed medical treatment or medical research. The basic legal tenet of modem informed consent is over 70 years old. Justice Cardozo stated that: "Every human being of adult years and sound mind has a right to determine what shall be done with his own body; and a surgeon who performs an oper- ation without his patient's consent commits an assault and battery for which he is liable in damages. . . [A person] is considered to be master of his own body, and he may, if he be of sound mind, expressly prohibit the perfor- mance of life-saving surgery or other medical treatment. . . The law does not promote [a physician] to substitute his own judgement for that of the patient." The American Hospital Association (AHA) has promulgated "A Patient's Bill of Rights" which states in part: "The patient has the right to receive from his physi- cian information necessary to give informed consent prior to the start of any proce- dure and/or treatment" and "The patient has the right to be advised if the hospital proposes to engage in or perform human experimentation affecting his care or treatment. The patient has the right to refuse to participate in such research projects." Another policy statement of the AHA deals with collaborative (physi- 38 cian and patient or research subject) decision-making as the basis for informed consent. The need for essential information to be present in the language familiar to the patient (or his parent or guardian) and the need for formal documentation of the presentation of such information have resulted in lengthy informed consent forms that are specific to the condition being treated. Gone are the "blanket" informed consent forms hospitals have used in the past. The medical and legal (professional) communities have long held that neonates and young children are not able to give meaningful consent for medical care and treatment. Parents are presumed to be in the best position to speak the mind of the child under the substituted judgment theory. Thus, parents or court-appointed legal guardians may give legally binding permission for children to receive medical treatments and also to become participants in research protocols. Few would argue about the appropriateness of the parent or guardian being the responsible person for authorizing medical treatment for their child or ward. Enrolling a child in a medical research protocol, however, is a more complex issue. Although the potential benefits of participation in research protocols (extended life or an improved quality of life) may often be substantial, many of these research protocols also may present substantial risks to the child. What are the decision-making processes that will maximize the potential benefits of medical science to the non- consenting child while protecting his or her fundamental rights? 7he Right ro Privacy The right to privacy is a fundamental constitutional right; this right may be overridden only by the demonstration of a compelling State interest. While minors are legally presumed not to be able to give informed consent or withhold consent for their medical care and treatment [in most jurisdictions this is an "irrebuttable" presumption (i.e., it cannot be successfully challenged in a court of law)], the parens patriae doctrine, the doctrine of informed consent in emergencies, the "Infant Doe" regulations of the United States Department of Health and Human Services, and numerous cases where a court-appointed guardianship is created to permit the treatment of a minor over the objections of the parent(s) (e.g., Jehovah's Witness' blood transfusion cases) - all support the general presumption that medical care and treatment should be provided to minors. Adults do have a right to refuse treatment, even if it will lead to their demise; they do not have the right to extend their personal beliefs to their children when the outcome of such an imposition is irreversible. The minor's personal right of privacy has been invoked when the guardians or parents, after determining that the minor is terminally ill and medical care offers no real hope of restoring health, have declined treatment. Historically, refusing necessary and life-saving treatment has constituted child abuse. In such circumstances the court may intervene, in parens patriae, to act as the general guardian, granting consent for the initiation of medical treatment. The court gener- ally will not intervene in this role to grant consent for the initiation of an experimental medical treatment. The final regulations of the Department of Health and Human Services to imple- ment the Child Abuse Amendments of 1984 to the Child Abuse Prevention and Treatment Act, 42 USC section 5101(a), enacted October 9, 1984, indicate that medical neglect (failure to provide adequate medical care) and withholding of medically indicated treatment, in the medical care of infants, are to be based on "reasonable medical judgment" and not on "quality of life standards." The final 39 rule requires that procedures be developed consistent with State law to obtain access to medical records and/or other pertinent information when such access is necessary to assure an appropriate investigation or a report of medical neglect. The Judicial Council of the American Medical Association states that the deci- sion whether to exert maximal efforts to sustain life should be the choice of the parents in consultation with the treating physician. Parental authority should be respected unless there is convincing evidence to the contrary. There is a substan- tive consensus on the deliberate withholding of life-saving treatment: 1) The law will support a decision not to provide treatment that would be futile or inhumane; no available treatment or surgical procedure offers any hope of survival; heroic efforts would be invasive, traumatic, and painful; medical opinion on diagnosis and prognosis is clear and unanimous. 2) The law will support terminating life-support for a patient whose brain has irreversibly ceased to function. 3) The law will defer, in matters of honest professional disagreement, to well-reasoned medical-ethical decisions which are the result of free and open communication among all concerned parties. The tension develops when, as in HIV infections, there is no acute decision to be made; the clinical course, though predictable, is not rapid; and the quantity of pain and suffering cannot be estimated, with any degree of medical certainty, before it occurs. The Duty to Warn Individuals with HIV antibodies have a right to medical confidentiality, but is it the physician's duty to warn those in foreseeable danger of contracting HIV from an infected individual? When, and under what circumstances should individual liberties, such as medical confidentiality, be abridged for the good of the community? If the female partner has not been notified that her male consort is seropositive or infected, becomes pregnant and delivers an infected child, is there liability? And for whom? The physician? The male consort? Both? These and other questions, basic to the medical care of children with a variety of health conditions, become all the more difficult when the condition is HIV infection. 40 MANAGEMENT OF THE CHILD WITH HIV IMPLICATIONS FOR SERVICE DELIVERY INFECTION: Mary G. Boland, R.N., M.S.N., C.P.N.P. Management of the Child with HIV Infection: Impact on Health Care Services In areas where HIV infection is epidemic, children with HIV infection and their families are straining the resources of health care delivery systems and human services agencies. The child and family have multiple medical, social, and emotional needs. The need for children to receive day care and attend school is forcing communities to deal with AIDS-related issues at the local level. While a small number of children acquire the disease as a result of transfusion of infected blood and blood products, the majority of infected children acquire AIDS perinatally. Mothers of these children are infected, and it is not unusual for both parents and one or more siblings to be infected and ill. Thus, the parents are confronted by issues regarding their own health status as well as that of the child. For the most part, children who get this disease and their parents are disen- franchised. They are not like the gay community, which is able to mobilize itself. They need health care providers who are not only sensitive to their needs but knowledgeable regarding the disease, and willing to advocate for the children and their families. About 80% of the children come from a home where one or both parents have a history of drug abuse. Because of problems related to drug use, many families are already receiving assistance from multiple health and human service agencies. The majority of the families are headed by a single parent, usually the mother, who is eligible for or receiving public assistance and Medicaid. After the diag- nosis, many of the children are eligible for and do receive Supplemental Security Income (SSI) and Medicaid. Prior to the diagnosis, 25% of the families in our program were known to the child protective services agency (Division of Youth and Family Services), and many were already in foster care. For most children, placement occurred because of unwillingness or inability of the mother to care for the child, rather than as a result of illness in the child. Active intravenous drug use resulted in inability of the mother to provide food and shelter for the child. In two families, acute encephalopathic symptoms in the mother required legal action and placement of the infant with other family members. We have no boarder babies in our institution and have a good record in terms of iden- tifying foster homes for our children when we have needed them. Initially, many of the mothers appeared well. However, as length of follow-up has increased, more mothers are becoming symptomatic,