- Email: [email protected]
The AIDS Epidemic: Past and Future
CHILDREN AFFECTED BY HIV I AIDS
1056-4993/00 $15.00 + .00
THE AIDS EPIDEMIC Past and Future Brian W. C. Forsyth, MBChB, FRCP(C)
Now at the end of its second decade, the AIDS epidemic is a major world crisis that affects the health and psychologic well-being of tens of millions of individuals, causes devastation among families, threatens the social welfare of communities, and impedes the economic progress of poor nations. The course of the epidemic is changing in different parts of the world: in North America and Europe the expansion of the epidemic has slowed; in sub-Saharan Africa, where rates of infection are already staggeringly high, the increasing spread of the epidemic continues; and in eastern Europe, which was relatively spared earlier in the epidemic, there now are rapidly emerging epidemics. There is a widening gap between developing and developed countries-countries with limited resources are experiencing dramatic escalations in the spread and effects of the epidemic whereas in countries such as the United States, where newer, expensive therapies are available, there have been significant decreases in morbidity and mortality. These differences are particularly true for children: in the developed world, where interventions aimed at reducing perinatal transmission are readily affordable, there has been a dramatic decrease in the number of perinatally infected children. This is not so in the developing world, however, where resources are lacking and there are many competing priorities, and reduction in perinatal transmission has not yet become a reality. Of particular concern is the increasing rate of infection among people younger than 25 years of age who now account for 50% of all new infections.
From the Department of Pediatrics, Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut
CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA VOLUME 9 • NUMBER 2 • APRIL 2000
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A WORLD VIEW OF THE EPIDEMIC
By the end of 1998 the number of people living with HIV infection was estimated to be 33.4 million, of which 95% are in the developing world (Fig. 1).38 According to estimates from the Joint United Nations Programme on HIV I AIDS (UNAIDS) and the World Health Organization (WHO), close to six million individuals were infected in 1998 alone and approximately 10% of these were younger than 15 years of age. There is an increasing trend for women to be infected, and women now account for 43% of all infected adults. Since the epidemic began, approximately 14 million adults and children have died. In 1998, approximately 2.5 million people died from AIDS, and it rose to become the fourth leading cause of death worldwide after being ranked seventh just 1 year previously.35 In comparison, malaria accounted for about 1 million deaths. These mortality statistics, however, do not portray the true extent of the effects of the epidemic, but serve as a prelude for the much more devastating results that are due to come as the epidemic ages and as people who are now infected but healthy become ill and die. Sub-Saharan Africa continues to dominate the world AIDS epidemic in sheer numbers. Approximately 70% of all new infections in 1998 occurred in this region and there were two million AIDS-related deaths. AIDS is now the leading cause of death in Africa, accounting for one in every five deaths. 35 Despite such devastation, there are many more people living with HIV infection- 21.5 million adults and 1 million children- who, without access to therapy, are expected to die in future years. Southern Africa is particularly hard hit: in Botswana, Namibia, Swaziland, and Zimbabwe, between 20% and 26% of people 15 to 49 years of age are already infected; and one in seven of all new infections
Figure 1. Adults and children estimated to be living with HIV and AIDS as of the end of 1998. Total: 33.4 million. (Courtesy of UNAIDS, United Nations Program on HIV/AIDS, Geneva, Switzerland, December, 1998.)
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on the continent now occurs in South Africa, a country that was relatively spared earlier in the epidemic. Rates of infection among pregnant women attending prenatal care have been found to be as high as 50% at one site in Zimbabwe. In other areas of the continent, infection rates are also very high; for example, more than 10% of the populations of the Central African Republic, Cote D'Ivoire, Djibouti, and Kenya are already infected. Although rates of infection are lower in other parts of the world, the numbers are still significant and show a rapid increase in some areas. By April 1999, there were approximately 7.2 million infected people in Asia, and approximately 20% of these were infected within the last year alone.35, 36 In South and Southeast Asia there were an estimated 1.2 million new infections in 1998, and approximately 700,000 of these were in young people and children. The highest HIV prevalence rates can be found in Cambodia, Thailand, Myanmar, and India. Epidemic spread is affected by changing economics, with people moving from rural to urban areas as economies expand, and then moving back to rural areas as unemployment rises. In India, for example, infection rates in rural areas are increasing and are now sometimes higher than in urban areas, unlike earlier in the epidemic. Prostitution is a major factor, as an increasing number of young women enter the sex trade for financial reasons. For example, in Phnom Penh the number of sex workers rose from about 1500 in 1990 to approximately 40,000 by the late 1990s, and in Battambang, Cambodia's second largest city, 40% of prostitutes are already infected with HIV. 36 In India nearly half of prostitutes are younger than 18 years of age. The epidemic in Latin America is similar to that in industrialized countries. Sex between men and intravenous drug use are the major modes of transmission, although there is also an increase in heterosexual transmission. This is particularly true in the Caribbean, where prevalence rates among pregnant women have been reported as high as 8% in Haiti and at one surveillance site in the Dominican Republic. 38 In Eastern Europe and Central Asia there is now an alarmingly sharp rise in HIV infections that is largely related to intravenous drug use. 37, 38 The number of cases in Eastern Europe increased ninefold in just 3 years, from less than 30,000 cases in 1995 to 270,000 cases by the end of 1998. Ukraine presently has the worst crisis, but the Russian Federation, Belarus, Moldova, and Kazakhstan also have rapidly escalating numbers. In each of these countries, epidemic spread is related to economic failure with the resulting increases in poverty and the disenfranchisement of young people. There is an increase in intravenous drug use and greater reliance on prostitution as a means of livelihood. There also has been a significant deterioration in health care systems, which together with changes in sexual behavior has contributed to dramatic increases in other sexually transmitted diseases such as syphilis. 15 In turn, lack of control of sexually transmitted diseases contributes to the expansion of the HIV epidemic, as the presence of other sexually transmitted diseases facilitates sexual transmission of HIV. 6, 16 To date, rates of condom use are low, and there
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is a tremendous need for effective interventions to quickly halt these rapidly emerging epidemics. THE EPIDEMIC IN THE UNITED STATES
In the United States, 1996 marked a major turning point in the epidemic when the introduction of new therapies slowed the progression of HIV disease, leading to a reduction in the number of AIDS cases and a dramatic decrease in HIV-related deaths (Fig. 2). As of December 1998, 688,200 Americans have been reported to have AIDS and 410,800 of these have died.7 In 1998 48,266 AIDS cases were reported to the Centers for Disease Control (CDC), which is only 65% of the number reported in 1996. Between 1996 and 1997, age-adjusted death rates from HIV infection fell an unprecedented 47% and HIV infection fell from the eighth to the fourteenth leading cause of death. 5 The 1997 age-adjusted HIV death rate was the lowest in a decade and approximately one third of that in 1995. AIDS had been the leading cause of death for those 25 to 44 years of age in 1995, but by 1997 it had fallen to the fifth leading cause of death for this age group.
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Figure 2. Estimated incidence of AIDS (triangles) and deaths (diamonds) of adults with AIDS (adjusted for reporting delays): 1985 to June 1998, United States. Trends in the incidence of AIDS must be viewed in light of changes in the history of the epidemic. The expansion of the case definition in 1993 created a large increase in the number of reported cases and required statistical adjustments to interpret the AIDS incidence data properly. Recent declines in AIDS incidence and deaths are primarily caused by the success of antiretroviral therapies introduced in 1996 that delay disease progression. (Courtesy of the Centers for Disease Control and Prevention, Atlanta, Georgia, 1999.)
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There continues to be other changes in the epidemic as it progresses. For example, women are increasingly affected: in 1998 women represented 23% of the reported cases of AIDS, whereas in the first 5 years of the epidemic only 7% were women.7 Blacks and Hispanics accounted for 45% and 20% of the cases reported in 1998 as compared with 25% and 14% of cases in the first 5 years of the epidemic. The largest single risk factor among men continues to be homosexual transmission (45% in 1998) and among women, heterosexual transmission (38%). Intravenous drug use accounted for 21 % and 29% of male and female cases, respectively. With more effective therapies delaying or preventing the onset of AIDS, however, statistics on AIDS fail to portray the true nature of the epidemic, and reporting of cases of HIV infection rather than statistics on AIDS is now a more accurate way of monitoring spread of the epidemic. Such reporting of cases of HIV infection has occurred in 25 states since 1994 and therefore provides information on the recent epidemic trend. Contrary to the declining rates of AIDS, these statistics show that the rate of spread of HIV infection remains fairly constant. Importantly, in the states where HIV was reported, 72% of cases were reported prior to an AIDS diagnosis.10 Reporting of HIV disease has also illustrated the fact that reliance on AIDS statistics tends to underrepresent women, African Americans, and those who contract the disease through heterosexual transmission. Data from HIV reporting between 1995 and 1996 showed that although HIV diagnoses declined slightly among men (-3%), there was an increase among women ( +3%). Similarly, there was a decrease among African Americans ( - 3%) and whites ( - 2% ), but an increase among Hispanics ( + 10% ). Statistics obtained from the 25 states that have had HIV reporting also provide important information on the spread of disease among youth. Because of the delay between the time of infection and the development of AIDS, statistics based on AIDS reporting have always tended to minimize the true extent of infection among adolescents. Of the 7200 cases of HIV disease reported among individuals between 13 and 24 years of age between 1994 and 1997, 44% were in girls, 63% were in African Americans, and at least 26% were heterosexually acquired. These statistics provide a more accurate picture of the HIV epidemic among young people and help focus the need for risk reduction efforts on these high-risk groups. WOMEN AND HIV INFECTION
In 1998 there were between 120,000 and 160,000 women living with HIV disease in the United States, and most of these were unaware of their HIV status. 21 Women of color are disproportionately affected; in 1998, 80% of the reported cases of women with AIDS were in African Americans or Hispanics.20 Most HIV-infected women are living in poverty, which, among other things, affects their access to health care. 30• 31
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Compared with men, poor women with HIV disease tend to have more advanced disease when they first enter care, and women of color are less likely than white women to receive medications. 26• 30 Because of the association with poverty and drug use, HIV-infected women may also experience other stressors, such as violence, that can contribute significantly to the level of psychologic distress. In a study of 2000 HIV-infected women, nearly 50% reported a history of sexual abuse and 60% experienced domestic violence. 21 For some women, there may be ongoing drug use, or, if a woman is not using drugs herself, her partner or other members of her family might continue to be involved with drugs. Almost two thirds of HIV-infected women are mothers, and for these women, the responsibilities of being a parent often take greater priority than dealing with the infection.21 CHILDREN AND AIDS
Changes in the incidence of AIDS have been even more dramatic in children than in adults. For example, in 1998 only 382 children were reported to the CDC with perinatally acquired AIDS, a mere 47% of the 894 cases reported in 1992. Although some of this reduction is the result of advances in therapy and the slowing of progression of disease as in adults, the greater contribution to this decline is the success in decreasing perinatal transmission from mother to child. In 1994, the results of a randomized clinical trial (ACTG 076) demonstrated that when Zidovudine (AZT) was given to HIV-infected women during pregnancy and labor and was given to their children for the first 6 weeks of infancy, the rate of transmission of HIV was reduced by approximately two thirds (from 24% to 8%).13 This finding was rapidly followed by recommendations by the Public Health Service for routine offering of HIV testing to pregnant women and treatment to women found to be infected.8 Introduction of this policy has had a rapid and dramatic effect- the rate of HIV transmission from infected mothers to their children is now below 6% in some areas of the country, 29 about 25% of what it was in earlier years. The recent confirmation that the rate of perinatal transmission can be lowered to about 2% when women are also offered the option of being delivered by cesarean section18• 23 is likely to further reduce the number of children being born with HIV disease in the United States and other countries where this is an affordable option. Preventing Perinatal Transmission of HIV in Developing Countries
Whereas decreasing the rate of perinatal transmission has altered the picture of pediatric AIDS in the developed world, the same successes have not been seen in poorer countries, where the protocol used in the ACTG 076 trial is unaffordable. The picture in developing countries is
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further complicated by the fact that HIV is also transmitted by breastfeeding. Between 15% and 30% of infants born to infected mothers contract the infection during pregnancy or at the time of birth, but in cultures where children are exclusively breastfed, an additional 10% to 20% contract the infection through breastfeeding.17 Substituting infant formula for breastfeeding is not only too expensive in most countries, but also is associated with an increased risk of morbidity and mortality from other infectious causes. 2• 25 Following the success of the ACTG 076 trial, a number of studies were initiated in developing countries to determine whether shorter and less expensive courses of antiretroviral therapy given to pregnant women might have a similar effect in decreasing perinatal transmission. Although some of these studies are not yet complete, the early results do demonstrate a beneficial effect, although not to the same extent as the ACTG 076 trial. A study performed in Thailand in a formula-feeding population resulted in the transmission rate being decreased by 50%,33 whereas other studies in breastfeeding populations in Africa had decreases in transmission rates of about 37%.14• 34 The preliminary results of a multisite, UNAIDS-sponsored study conducted in a population that included both formula-feeding and breastfeeding infants demonstrated that transmission can be decreased by about one third even if antiretroviral therapy isn't started until after women go into labor. 32 Obviously, this means that far less medication is needed and therefore treatment is significantly less expensive. Whether or not the countries that have the highest rates of HIV disease can successfully introduce programs to prevent perinatal transmission is still to be seen. Implementation of such intervention not only requires access to affordable medications, but also a sound system for providing prenatal and perinatal care, as well as HIV testing with counseling. Even when women agree to testing, a large proportion do not return for the results: a survey of researchers conducting 13 different studies offering potential treatments to pregnant women in developing countries showed that on average only 69% of the women both accepted testing and returned for the results. 3 In addition if a woman is found to be positive, she then needs to be able to adhere to taking her medication. Obviously, fears of stigmatization or, even worse, fears of abuse or being thrown out of her home might interfere with a woman getting tested, or might cause her not to take her medication. 27 Orphans
Although there is a real opportunity to decrease the number of children being infected with HIV, the number of infected adults worldwide continues to increase, resulting in a rapidly escalating number of children orphaned by the epidemic. According to UNAIDS statistics, by the end of 1997 approximately 8.2 million children younger than 15 years of age had lost their mothers, or possibly both parents, to the
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disease and over 95% of these orphans live in sub-Saharan Africa. 38 One third of the children orphaned by AIDS are younger than 5 years of age. In the United States, early projections were that by the end of the century the number of motherless children and adolescents would exceed 80,000. 28 The decrease in mortality since these projections were made, however, suggests that the actual number is likely lower. In the developing world, the picture is very different. Studies done in the early 1990s showed that the number of orphans was already high; for example, in a rural community in Uganda, more than 10% of the children had lost a parent, 24 and in a study done in Zimbabwe, 14.7% of children were already orphaned. 19 Such figures will continue to parallel the increasing rate of infection among adults. Orph•med rhildrf'n are most often looked after by members of the extended family, frequently aging grandparents, or sometimes adolescent siblings. As the infection rate in a community increases, however, there are fewer working adults and fewer resources available to care for orphaned children. ADOLESCENTS AND YOUTH
Young people are disproportionately affected by the HIV epidemic. Worldwide it is now estimated that about half of all new HIV infections occur in people younger than 25 years of age. 38 In 1998 nearly three million young people became infected with the virus, and the infection rate is tending to increase more rapidly among youth than it is among older individuals. In the United States, even though there is a decline in AIDS incidence, there has not been a comparable decline in the number of newly diagnosed cases of HIV infection among young people.11 Unlike in the older population, in the adolescent age range HIV infection tends to be more prevalent among girls than among boys. Rates of infection with other sexually transmitted diseases continue to be very high among youth and serve as an indicator of the high risk for HIV infection among this age group. Of the 12 million cases of sexually transmitted diseases reported in the United States each year, one quarter occur among teenagers and two thirds are acquired by 25 years of age. 12 Drug use among adolescents can also increase the risk of HIV infection, not only through direct infection from intravenous drug use, but also through increased risk for unsafe sexual activity when inhibitions are lowered from use of alcohol or other drugs. WHAT DOES THE FUTURE HOLD?
Throughout the world, the major focus continues to be on decreasing the risks of transmission through changing people's behavior, whether this be unsafe sexual practices or intravenous drug use. Although general trends are disappointing, many initiatives have had some success. For example, an intervention in Thailand focused on
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increasing condom use resulted in an increase in condom use and a decrease in the incidence of sexually transmitted diseases and HIV. 4 Similarly, in Senegal a program focused on sex workers led to a significant drop in sexually transmitted diseases. 38 Both in the developed world and in some countries in Africa, there has been a leveling off of new infections, which is likely a result of such intervention efforts. There is some evidence that young people might be more likely to adopt safer sex practices than older individuals. Studies done in Chile and Brazil have shown that compared with older adults, a higher proportion of young people use condoms, and in the United States there has been a rise in the proportion of high school students reporting either sexual abstinence or condom use. In a survey done in 1997, 63% of boys reported condom use at the time of last intercourse compared with 55% in a similar survey conducted 6 years earlier. For girls, the proportion increased to 51 % from 38% in the same time period.9 Other approaches to decreasing HIV transmission are also being tried. For example, in Africa, antibiotics are being used more widely for the treatment of sexually transmitted diseases that contribute to risk of HIV transmission. Development of a "female condom" has allowed women to have more control over their own protection, and research continues into potential virocides that could be used to decrease sexual transmission. It is well recognized, however, that there are unlikely to be major advances in slowing the epidemic without a breakthrough in development of a vaccine to prevent HIV infection, which, to date, has been painstakingly slow. Certainly variability in the virus has been the most important problem facing HIV vaccine researchers, but there are many hurdles to overcome, including major ethical concerns that surround clinical trials. 1• 22 A live attenuated virus that has multiple deletions to its genome is considered by many to be the best approach, but there are major concerns about the potential for developing a vaccine that could in fact be pathogenic. Although presently there are more than 25 candidate vaccines being examined, by the end of 1998 there were only two vaccines in large-scale clinical trials designed to test their efficacy, one in the United States and a second in Thailand. Results from these studies will not be available until 2003. SUMMARY
As we near the end of the second decade of AIDS, this global epidemic is characterized by a widening gap between wealthier nations in North America and Europe and the poorer nations of the world. In developed countries the epidemic has stabilized and there are dramatic decreases in morbidity and mortality resulting from the use of intensive but expensive therapies. This contrasts with the experience of poorer nations, where the epidemic's spread is often unabated and has devastating effects on communities, families, and individuals. A decrease in
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transmission from mothers to their children is a possibility that still needs to be realized in developing countries, although the potential now exists. Adolescents and young adults are most at risk for contracting the infection, and, recognizing that an effective vaccine is unlikely to be a reality for many years, there is great need for culturally appropriate and innovative means of affecting behavior to decrease the risk of transmission. Although the extent of children's suffering through the loss of their parents has already been felt worldwide, the extreme magnitude of this is still to come, particularly in those countries and communities that have the least resources. The epidemic is a global problem, and addressing the disease and its consequences on children and youth worldwide requires an international response. The potential for complacency in developed countries needs to be replaced by a determination to bridge existing gaps. This requires the focus and support of governments, international agencies such as UNAIDS, nongovernmental organizations, corporations (particularly those that produce antiretroviral medications and artificial milk formulas), researchers from many disciplines, and other individuals.
References 1. Anonymous: The HIV vaccine: How long must be wait? Lancet 352:1323, 1998 2. Butz WP, Habicht JP, Vanzo DA: Environmental factors in the relationship between breast-feeding and infant mortality. The role of sanitation and water in Malaysia. Am J Epidemiol 119:516-525, 1984 3. Cartoux M, Meda N, Van de Perre P, et al: Acceptability of voluntary HIV testing by pregnant women in developing countries: An international survey. AIDS 12:24892493, 1998 4. Celentano DD, Nelson KE, Lyles CM, et al: Decreasing incidence of HIV and sexually transmitted diseases in young Thai men: Evidence for success of the HIV I AIDS control and prevention program. AIDS 12:F29-F36, 1998 5. Centers for Disease Control and Prevention: AIDS falls from top ten causes of death; teen births, infant mortality, homicide all decline. Atlanta, GA, CDC, 1998 6. Centers for Disease Control and Prevention: Critical need to pay attention to HIV prevention for women: Minority and young women bear greatest burden. CDC Fact Sheet. Atlanta, GA, CDC, 1998 7. Centers for Disease Control and Prevention: HIV I AIDS Surveillance Report, U.S. HIV and AIDS cases reported through December, 1998, Year-end edition, vol 10. Atlanta, GA, CDC, 1999 8. Centers for Disease Control and Prevention: Recommendations of the U.S. Public Health Service Task Force on the use of zidovudine to reduce perinatal transmission of human immunodeficiency virus. MMWR Morb Mortal Wkly Rep 43:1-20, 1994 9. Centers for Disease Control and Prevention: Trends in sexual risk behaviors among high school students-United States, 1991-1997. MMWR Morb Mortal Wkly Rep 47(36):749-752, 1998 10. Centers for Disease Control and Prevention: Trends in the HIV & AIDS Epidemic. Atlanta, GA, CDC, 1998 11. Centers for Disease Control and Prevention: Young people at risk-Epidemic shifts further toward young women and minorities. CDC Update. Atlanta, GA, CDC, 1998 12. Chabon B, Futterman D: Adolescents and HIV. AIDS Clinical Care 11:9-15, 1999 13. Connor EM, Sperling RS, Gelber R, et al: Reduction of maternal-infant transmission of
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human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med 331:1173-1180, 1994 14. Dabis F, Msellati P, Meda N, et al: Six-month efficacy, tolerance, and acceptability of a short course regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Cote d'Ivoire and Burkina Faso: A double-blind placebo-controlled trial. Lancet 353:786-792, 1999 15. Dehne KL, Khodakevich L, Hamers FF, et al: The HIV I AIDS epidemic in eastern Europe: Recent patterns and trends and their implications for policy-making. AIDS 13:741-749, 1999 16. Division of STD Prevention: Sexually Transmitted Disease Surveillance, 1997. U.S. Department of Health and Human Services, Public Health Service. Atlanta, CDC, 1998 17. Dunn DT, Newell ML, Ades AE, et al: Risk of human immunodeficiency virus type 1 transmission through breastfeeding. Lancet 340:585-588, 1992 18. The European Mode of Delivery Collaboration: Elective caesarean-section versus vaginal delivery in prevention of vertical transmission: A randomized clinical trial. Lancet 353:1035-1039, 1999 19. Foster G, Makufa C, Drew R, et al: Supporting children in need through a communitybased orphan visiting programme. AIDS Care 8:389-403, 1996 20. Health Resources and Service Administration: HIV disease in women of color. Rockville, HRSA Care Action, 1999, pp 1-3 21. Health Resources and Services Administration: Women and HIV I AIDS. Rockville, HRSA Care Action, 1998, pp 1-4 22. Heyward WL, MacQueen KM, Goldenthal KL: HIV vaccine development and evaluation: Realistic expectations. AIDS Research and Human Retroviruses 14 (suppl 3):S205S210, 1998 23. The International Perinatal HIV Group: The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1. N Engl J Med 340:977-987, 1999 24. Kamali A, Seeley JA, Nunn AJ, et al: The orphan problem: Experience of a sub-Saharan Africa rural population in the AIDS epidemic. AIDS Care 8:509-515, 1996 25. Kuhn L, Stein Z: Infant survival, HIV infection, and feeding alternatives in lessdeveloped countries. Am J Public Health 87:926-931, 1997 26. Lopez OL, Wess J, Sanchez J, et al: Neurobehavioral and medical differences between HIV-infected men and women. (Abstract Pl.42). In Programs and Abstracts of the National Conference on Women and HIV. 1997 27. Meursing K: A world of silence: Living with HIV in Matabeleland, Zimbabwe. Amsterdam, Royal Tropical Institute, 1997 28. Michaels D, Levine C: Estimates of the number of motherless youth orphaned by AIDS in the United States. JAMA 268:3456-3461, 1992 29. Mofensen LM: Short-course zidovudine for prevention of perinatal infection. Lancet 353:766-767, 1999 30. Odem S, Sorvillo F, Kerndt P, et al: The prescription of protease inhibitors among women with AIDS in Los Angeles County [abstract 304.5]. In Programs and Abstracts of the National Conference on Women and HIV. 1997 31. Russell JM, Smith K: HIV-infected women and women's services. Health Care Women International 19:131-139, 1998 32. Saba J: The results of the PETRA intervention trial to prevent perinatal transmission in sub-Saharan Africa. Symposium Session 8. Sixth Conference on Retroviruses and Opportunistic Infections. Chicago, IL, January 31-February 4, 1999 33. Shaffer N, Chuachoowong R, Mock PA, et al: Short-course zidovudine for perinatal HIV transmission in Bangkok, Thailand: A randomised controlled trial. Lancet 353:773780, 1999 34. Wiktor SZ, Ekpini E, Karon JM, et al: Short-course oral zidovudine for prevention of mother-to-child transmission of HIV-1 in Abidjan, Cote d'Ivoire: A randomised trial. Lancet 353:781-785, 1999 35. UNAIDS: AIDS moves to fourth place among world killers. Press release. Geneva, UNAIDS, May 11, 1999 36. UNAIDS: Asia facing increasing HIV spread among children and young people;
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economic crisis may intensify AIDS risks. Press release. Bangkok, UNAIDS, April 2, 1999 37. UN AIDS: Structural collapse sets the scene for the rapid spread of HIV I AIDS among young people in eastern Europe. Press release. Kiev, UNAIDS, May 12, 1999 38. UNAIDS Joint United Nations Programme on HIV I AIDS: AIDS Epidemic Update. New York, United Nations, 1998
Address reprint requests to Brian W. C. Forsyth, MB ChB, FRCP(C) Department of Pediatrics Yale University School of Medicine 333 Cedar Street New Haven, CT 06520-8064 e-mail: [email protected]
1056-4993/00 $15.00 + .00
THE AIDS EPIDEMIC Past and Future Brian W. C. Forsyth, MBChB, FRCP(C)
Now at the end of its second decade, the AIDS epidemic is a major world crisis that affects the health and psychologic well-being of tens of millions of individuals, causes devastation among families, threatens the social welfare of communities, and impedes the economic progress of poor nations. The course of the epidemic is changing in different parts of the world: in North America and Europe the expansion of the epidemic has slowed; in sub-Saharan Africa, where rates of infection are already staggeringly high, the increasing spread of the epidemic continues; and in eastern Europe, which was relatively spared earlier in the epidemic, there now are rapidly emerging epidemics. There is a widening gap between developing and developed countries-countries with limited resources are experiencing dramatic escalations in the spread and effects of the epidemic whereas in countries such as the United States, where newer, expensive therapies are available, there have been significant decreases in morbidity and mortality. These differences are particularly true for children: in the developed world, where interventions aimed at reducing perinatal transmission are readily affordable, there has been a dramatic decrease in the number of perinatally infected children. This is not so in the developing world, however, where resources are lacking and there are many competing priorities, and reduction in perinatal transmission has not yet become a reality. Of particular concern is the increasing rate of infection among people younger than 25 years of age who now account for 50% of all new infections.
From the Department of Pediatrics, Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut
CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA VOLUME 9 • NUMBER 2 • APRIL 2000
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A WORLD VIEW OF THE EPIDEMIC
By the end of 1998 the number of people living with HIV infection was estimated to be 33.4 million, of which 95% are in the developing world (Fig. 1).38 According to estimates from the Joint United Nations Programme on HIV I AIDS (UNAIDS) and the World Health Organization (WHO), close to six million individuals were infected in 1998 alone and approximately 10% of these were younger than 15 years of age. There is an increasing trend for women to be infected, and women now account for 43% of all infected adults. Since the epidemic began, approximately 14 million adults and children have died. In 1998, approximately 2.5 million people died from AIDS, and it rose to become the fourth leading cause of death worldwide after being ranked seventh just 1 year previously.35 In comparison, malaria accounted for about 1 million deaths. These mortality statistics, however, do not portray the true extent of the effects of the epidemic, but serve as a prelude for the much more devastating results that are due to come as the epidemic ages and as people who are now infected but healthy become ill and die. Sub-Saharan Africa continues to dominate the world AIDS epidemic in sheer numbers. Approximately 70% of all new infections in 1998 occurred in this region and there were two million AIDS-related deaths. AIDS is now the leading cause of death in Africa, accounting for one in every five deaths. 35 Despite such devastation, there are many more people living with HIV infection- 21.5 million adults and 1 million children- who, without access to therapy, are expected to die in future years. Southern Africa is particularly hard hit: in Botswana, Namibia, Swaziland, and Zimbabwe, between 20% and 26% of people 15 to 49 years of age are already infected; and one in seven of all new infections
Figure 1. Adults and children estimated to be living with HIV and AIDS as of the end of 1998. Total: 33.4 million. (Courtesy of UNAIDS, United Nations Program on HIV/AIDS, Geneva, Switzerland, December, 1998.)
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on the continent now occurs in South Africa, a country that was relatively spared earlier in the epidemic. Rates of infection among pregnant women attending prenatal care have been found to be as high as 50% at one site in Zimbabwe. In other areas of the continent, infection rates are also very high; for example, more than 10% of the populations of the Central African Republic, Cote D'Ivoire, Djibouti, and Kenya are already infected. Although rates of infection are lower in other parts of the world, the numbers are still significant and show a rapid increase in some areas. By April 1999, there were approximately 7.2 million infected people in Asia, and approximately 20% of these were infected within the last year alone.35, 36 In South and Southeast Asia there were an estimated 1.2 million new infections in 1998, and approximately 700,000 of these were in young people and children. The highest HIV prevalence rates can be found in Cambodia, Thailand, Myanmar, and India. Epidemic spread is affected by changing economics, with people moving from rural to urban areas as economies expand, and then moving back to rural areas as unemployment rises. In India, for example, infection rates in rural areas are increasing and are now sometimes higher than in urban areas, unlike earlier in the epidemic. Prostitution is a major factor, as an increasing number of young women enter the sex trade for financial reasons. For example, in Phnom Penh the number of sex workers rose from about 1500 in 1990 to approximately 40,000 by the late 1990s, and in Battambang, Cambodia's second largest city, 40% of prostitutes are already infected with HIV. 36 In India nearly half of prostitutes are younger than 18 years of age. The epidemic in Latin America is similar to that in industrialized countries. Sex between men and intravenous drug use are the major modes of transmission, although there is also an increase in heterosexual transmission. This is particularly true in the Caribbean, where prevalence rates among pregnant women have been reported as high as 8% in Haiti and at one surveillance site in the Dominican Republic. 38 In Eastern Europe and Central Asia there is now an alarmingly sharp rise in HIV infections that is largely related to intravenous drug use. 37, 38 The number of cases in Eastern Europe increased ninefold in just 3 years, from less than 30,000 cases in 1995 to 270,000 cases by the end of 1998. Ukraine presently has the worst crisis, but the Russian Federation, Belarus, Moldova, and Kazakhstan also have rapidly escalating numbers. In each of these countries, epidemic spread is related to economic failure with the resulting increases in poverty and the disenfranchisement of young people. There is an increase in intravenous drug use and greater reliance on prostitution as a means of livelihood. There also has been a significant deterioration in health care systems, which together with changes in sexual behavior has contributed to dramatic increases in other sexually transmitted diseases such as syphilis. 15 In turn, lack of control of sexually transmitted diseases contributes to the expansion of the HIV epidemic, as the presence of other sexually transmitted diseases facilitates sexual transmission of HIV. 6, 16 To date, rates of condom use are low, and there
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is a tremendous need for effective interventions to quickly halt these rapidly emerging epidemics. THE EPIDEMIC IN THE UNITED STATES
In the United States, 1996 marked a major turning point in the epidemic when the introduction of new therapies slowed the progression of HIV disease, leading to a reduction in the number of AIDS cases and a dramatic decrease in HIV-related deaths (Fig. 2). As of December 1998, 688,200 Americans have been reported to have AIDS and 410,800 of these have died.7 In 1998 48,266 AIDS cases were reported to the Centers for Disease Control (CDC), which is only 65% of the number reported in 1996. Between 1996 and 1997, age-adjusted death rates from HIV infection fell an unprecedented 47% and HIV infection fell from the eighth to the fourteenth leading cause of death. 5 The 1997 age-adjusted HIV death rate was the lowest in a decade and approximately one third of that in 1995. AIDS had been the leading cause of death for those 25 to 44 years of age in 1995, but by 1997 it had fallen to the fifth leading cause of death for this age group.
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Figure 2. Estimated incidence of AIDS (triangles) and deaths (diamonds) of adults with AIDS (adjusted for reporting delays): 1985 to June 1998, United States. Trends in the incidence of AIDS must be viewed in light of changes in the history of the epidemic. The expansion of the case definition in 1993 created a large increase in the number of reported cases and required statistical adjustments to interpret the AIDS incidence data properly. Recent declines in AIDS incidence and deaths are primarily caused by the success of antiretroviral therapies introduced in 1996 that delay disease progression. (Courtesy of the Centers for Disease Control and Prevention, Atlanta, Georgia, 1999.)
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There continues to be other changes in the epidemic as it progresses. For example, women are increasingly affected: in 1998 women represented 23% of the reported cases of AIDS, whereas in the first 5 years of the epidemic only 7% were women.7 Blacks and Hispanics accounted for 45% and 20% of the cases reported in 1998 as compared with 25% and 14% of cases in the first 5 years of the epidemic. The largest single risk factor among men continues to be homosexual transmission (45% in 1998) and among women, heterosexual transmission (38%). Intravenous drug use accounted for 21 % and 29% of male and female cases, respectively. With more effective therapies delaying or preventing the onset of AIDS, however, statistics on AIDS fail to portray the true nature of the epidemic, and reporting of cases of HIV infection rather than statistics on AIDS is now a more accurate way of monitoring spread of the epidemic. Such reporting of cases of HIV infection has occurred in 25 states since 1994 and therefore provides information on the recent epidemic trend. Contrary to the declining rates of AIDS, these statistics show that the rate of spread of HIV infection remains fairly constant. Importantly, in the states where HIV was reported, 72% of cases were reported prior to an AIDS diagnosis.10 Reporting of HIV disease has also illustrated the fact that reliance on AIDS statistics tends to underrepresent women, African Americans, and those who contract the disease through heterosexual transmission. Data from HIV reporting between 1995 and 1996 showed that although HIV diagnoses declined slightly among men (-3%), there was an increase among women ( +3%). Similarly, there was a decrease among African Americans ( - 3%) and whites ( - 2% ), but an increase among Hispanics ( + 10% ). Statistics obtained from the 25 states that have had HIV reporting also provide important information on the spread of disease among youth. Because of the delay between the time of infection and the development of AIDS, statistics based on AIDS reporting have always tended to minimize the true extent of infection among adolescents. Of the 7200 cases of HIV disease reported among individuals between 13 and 24 years of age between 1994 and 1997, 44% were in girls, 63% were in African Americans, and at least 26% were heterosexually acquired. These statistics provide a more accurate picture of the HIV epidemic among young people and help focus the need for risk reduction efforts on these high-risk groups. WOMEN AND HIV INFECTION
In 1998 there were between 120,000 and 160,000 women living with HIV disease in the United States, and most of these were unaware of their HIV status. 21 Women of color are disproportionately affected; in 1998, 80% of the reported cases of women with AIDS were in African Americans or Hispanics.20 Most HIV-infected women are living in poverty, which, among other things, affects their access to health care. 30• 31
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Compared with men, poor women with HIV disease tend to have more advanced disease when they first enter care, and women of color are less likely than white women to receive medications. 26• 30 Because of the association with poverty and drug use, HIV-infected women may also experience other stressors, such as violence, that can contribute significantly to the level of psychologic distress. In a study of 2000 HIV-infected women, nearly 50% reported a history of sexual abuse and 60% experienced domestic violence. 21 For some women, there may be ongoing drug use, or, if a woman is not using drugs herself, her partner or other members of her family might continue to be involved with drugs. Almost two thirds of HIV-infected women are mothers, and for these women, the responsibilities of being a parent often take greater priority than dealing with the infection.21 CHILDREN AND AIDS
Changes in the incidence of AIDS have been even more dramatic in children than in adults. For example, in 1998 only 382 children were reported to the CDC with perinatally acquired AIDS, a mere 47% of the 894 cases reported in 1992. Although some of this reduction is the result of advances in therapy and the slowing of progression of disease as in adults, the greater contribution to this decline is the success in decreasing perinatal transmission from mother to child. In 1994, the results of a randomized clinical trial (ACTG 076) demonstrated that when Zidovudine (AZT) was given to HIV-infected women during pregnancy and labor and was given to their children for the first 6 weeks of infancy, the rate of transmission of HIV was reduced by approximately two thirds (from 24% to 8%).13 This finding was rapidly followed by recommendations by the Public Health Service for routine offering of HIV testing to pregnant women and treatment to women found to be infected.8 Introduction of this policy has had a rapid and dramatic effect- the rate of HIV transmission from infected mothers to their children is now below 6% in some areas of the country, 29 about 25% of what it was in earlier years. The recent confirmation that the rate of perinatal transmission can be lowered to about 2% when women are also offered the option of being delivered by cesarean section18• 23 is likely to further reduce the number of children being born with HIV disease in the United States and other countries where this is an affordable option. Preventing Perinatal Transmission of HIV in Developing Countries
Whereas decreasing the rate of perinatal transmission has altered the picture of pediatric AIDS in the developed world, the same successes have not been seen in poorer countries, where the protocol used in the ACTG 076 trial is unaffordable. The picture in developing countries is
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further complicated by the fact that HIV is also transmitted by breastfeeding. Between 15% and 30% of infants born to infected mothers contract the infection during pregnancy or at the time of birth, but in cultures where children are exclusively breastfed, an additional 10% to 20% contract the infection through breastfeeding.17 Substituting infant formula for breastfeeding is not only too expensive in most countries, but also is associated with an increased risk of morbidity and mortality from other infectious causes. 2• 25 Following the success of the ACTG 076 trial, a number of studies were initiated in developing countries to determine whether shorter and less expensive courses of antiretroviral therapy given to pregnant women might have a similar effect in decreasing perinatal transmission. Although some of these studies are not yet complete, the early results do demonstrate a beneficial effect, although not to the same extent as the ACTG 076 trial. A study performed in Thailand in a formula-feeding population resulted in the transmission rate being decreased by 50%,33 whereas other studies in breastfeeding populations in Africa had decreases in transmission rates of about 37%.14• 34 The preliminary results of a multisite, UNAIDS-sponsored study conducted in a population that included both formula-feeding and breastfeeding infants demonstrated that transmission can be decreased by about one third even if antiretroviral therapy isn't started until after women go into labor. 32 Obviously, this means that far less medication is needed and therefore treatment is significantly less expensive. Whether or not the countries that have the highest rates of HIV disease can successfully introduce programs to prevent perinatal transmission is still to be seen. Implementation of such intervention not only requires access to affordable medications, but also a sound system for providing prenatal and perinatal care, as well as HIV testing with counseling. Even when women agree to testing, a large proportion do not return for the results: a survey of researchers conducting 13 different studies offering potential treatments to pregnant women in developing countries showed that on average only 69% of the women both accepted testing and returned for the results. 3 In addition if a woman is found to be positive, she then needs to be able to adhere to taking her medication. Obviously, fears of stigmatization or, even worse, fears of abuse or being thrown out of her home might interfere with a woman getting tested, or might cause her not to take her medication. 27 Orphans
Although there is a real opportunity to decrease the number of children being infected with HIV, the number of infected adults worldwide continues to increase, resulting in a rapidly escalating number of children orphaned by the epidemic. According to UNAIDS statistics, by the end of 1997 approximately 8.2 million children younger than 15 years of age had lost their mothers, or possibly both parents, to the
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disease and over 95% of these orphans live in sub-Saharan Africa. 38 One third of the children orphaned by AIDS are younger than 5 years of age. In the United States, early projections were that by the end of the century the number of motherless children and adolescents would exceed 80,000. 28 The decrease in mortality since these projections were made, however, suggests that the actual number is likely lower. In the developing world, the picture is very different. Studies done in the early 1990s showed that the number of orphans was already high; for example, in a rural community in Uganda, more than 10% of the children had lost a parent, 24 and in a study done in Zimbabwe, 14.7% of children were already orphaned. 19 Such figures will continue to parallel the increasing rate of infection among adults. Orph•med rhildrf'n are most often looked after by members of the extended family, frequently aging grandparents, or sometimes adolescent siblings. As the infection rate in a community increases, however, there are fewer working adults and fewer resources available to care for orphaned children. ADOLESCENTS AND YOUTH
Young people are disproportionately affected by the HIV epidemic. Worldwide it is now estimated that about half of all new HIV infections occur in people younger than 25 years of age. 38 In 1998 nearly three million young people became infected with the virus, and the infection rate is tending to increase more rapidly among youth than it is among older individuals. In the United States, even though there is a decline in AIDS incidence, there has not been a comparable decline in the number of newly diagnosed cases of HIV infection among young people.11 Unlike in the older population, in the adolescent age range HIV infection tends to be more prevalent among girls than among boys. Rates of infection with other sexually transmitted diseases continue to be very high among youth and serve as an indicator of the high risk for HIV infection among this age group. Of the 12 million cases of sexually transmitted diseases reported in the United States each year, one quarter occur among teenagers and two thirds are acquired by 25 years of age. 12 Drug use among adolescents can also increase the risk of HIV infection, not only through direct infection from intravenous drug use, but also through increased risk for unsafe sexual activity when inhibitions are lowered from use of alcohol or other drugs. WHAT DOES THE FUTURE HOLD?
Throughout the world, the major focus continues to be on decreasing the risks of transmission through changing people's behavior, whether this be unsafe sexual practices or intravenous drug use. Although general trends are disappointing, many initiatives have had some success. For example, an intervention in Thailand focused on
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increasing condom use resulted in an increase in condom use and a decrease in the incidence of sexually transmitted diseases and HIV. 4 Similarly, in Senegal a program focused on sex workers led to a significant drop in sexually transmitted diseases. 38 Both in the developed world and in some countries in Africa, there has been a leveling off of new infections, which is likely a result of such intervention efforts. There is some evidence that young people might be more likely to adopt safer sex practices than older individuals. Studies done in Chile and Brazil have shown that compared with older adults, a higher proportion of young people use condoms, and in the United States there has been a rise in the proportion of high school students reporting either sexual abstinence or condom use. In a survey done in 1997, 63% of boys reported condom use at the time of last intercourse compared with 55% in a similar survey conducted 6 years earlier. For girls, the proportion increased to 51 % from 38% in the same time period.9 Other approaches to decreasing HIV transmission are also being tried. For example, in Africa, antibiotics are being used more widely for the treatment of sexually transmitted diseases that contribute to risk of HIV transmission. Development of a "female condom" has allowed women to have more control over their own protection, and research continues into potential virocides that could be used to decrease sexual transmission. It is well recognized, however, that there are unlikely to be major advances in slowing the epidemic without a breakthrough in development of a vaccine to prevent HIV infection, which, to date, has been painstakingly slow. Certainly variability in the virus has been the most important problem facing HIV vaccine researchers, but there are many hurdles to overcome, including major ethical concerns that surround clinical trials. 1• 22 A live attenuated virus that has multiple deletions to its genome is considered by many to be the best approach, but there are major concerns about the potential for developing a vaccine that could in fact be pathogenic. Although presently there are more than 25 candidate vaccines being examined, by the end of 1998 there were only two vaccines in large-scale clinical trials designed to test their efficacy, one in the United States and a second in Thailand. Results from these studies will not be available until 2003. SUMMARY
As we near the end of the second decade of AIDS, this global epidemic is characterized by a widening gap between wealthier nations in North America and Europe and the poorer nations of the world. In developed countries the epidemic has stabilized and there are dramatic decreases in morbidity and mortality resulting from the use of intensive but expensive therapies. This contrasts with the experience of poorer nations, where the epidemic's spread is often unabated and has devastating effects on communities, families, and individuals. A decrease in
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transmission from mothers to their children is a possibility that still needs to be realized in developing countries, although the potential now exists. Adolescents and young adults are most at risk for contracting the infection, and, recognizing that an effective vaccine is unlikely to be a reality for many years, there is great need for culturally appropriate and innovative means of affecting behavior to decrease the risk of transmission. Although the extent of children's suffering through the loss of their parents has already been felt worldwide, the extreme magnitude of this is still to come, particularly in those countries and communities that have the least resources. The epidemic is a global problem, and addressing the disease and its consequences on children and youth worldwide requires an international response. The potential for complacency in developed countries needs to be replaced by a determination to bridge existing gaps. This requires the focus and support of governments, international agencies such as UNAIDS, nongovernmental organizations, corporations (particularly those that produce antiretroviral medications and artificial milk formulas), researchers from many disciplines, and other individuals.
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Address reprint requests to Brian W. C. Forsyth, MB ChB, FRCP(C) Department of Pediatrics Yale University School of Medicine 333 Cedar Street New Haven, CT 06520-8064 e-mail: [email protected]