Summary of Findings: Preventing Perinatal Transmission of HIV

  • To date, an estimated 3.8 million children have died of HIV/AIDS. The vast majority of these children acquired HIV from their mothers during pregnancy, childbirth, or breastfeeding.

  • In parts of southern Africa, 30 percent or more of pregnant women are infected with HIV, and 25 to 35 percent of their children become infected.

  • Considerable evidence indicates that treating pregnant women who are HIV-positive and their infants with simple low-cost regimens of antiretroviral drugs is the most feasible and cost-effective means to prevent perinatal HIV transmission in developing countries.

  • The stigma and discrimination borne by women who test positive for HIV/AIDS present significant additional problems to their physical illness.

  • Counseling women on the risks and benefits of antenatal HIV screening and treatment must be incorporated into antenatal care, along with options for HIV screening and antiretroviral prophylaxis.



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Improving Birth Outcomes: Meeting the Challenge in the Developing World Summary of Findings: Preventing Perinatal Transmission of HIV To date, an estimated 3.8 million children have died of HIV/AIDS. The vast majority of these children acquired HIV from their mothers during pregnancy, childbirth, or breastfeeding. In parts of southern Africa, 30 percent or more of pregnant women are infected with HIV, and 25 to 35 percent of their children become infected. Considerable evidence indicates that treating pregnant women who are HIV-positive and their infants with simple low-cost regimens of antiretroviral drugs is the most feasible and cost-effective means to prevent perinatal HIV transmission in developing countries. The stigma and discrimination borne by women who test positive for HIV/AIDS present significant additional problems to their physical illness. Counseling women on the risks and benefits of antenatal HIV screening and treatment must be incorporated into antenatal care, along with options for HIV screening and antiretroviral prophylaxis.

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Improving Birth Outcomes: Meeting the Challenge in the Developing World 8 Preventing Perinatal Transmission of HIV The transmission of HIV from mother to fetus or infant presents a pressing challenge to improving birth outcomes in many developing countries. Since the start of the AIDS epidemic, an estimated 3.8 million children have died of the disease. The vast majority of these children acquired HIV from their mothers during pregnancy, at the time of childbirth, or during breastfeeding. Antiretroviral drugs that can be delivered to the mother during pregnancy and labor and to the child after birth, and which are widely used in the United States and other developed countries, have the potential to reverse the epidemic of pediatric AIDS in developing countries (Mofenson and McIntyre, 2000; Coll et al., 2002). Despite their promise, however, such interventions are not common in the developing world. This chapter describes the scope of the HIV/AIDS epidemic, focusing on heavily infected populations where mother-to-child transmission occurs most frequently, and reviews the evidence for a variety of potential interventions to prevent perinatal transmission of HIV. It concludes with a description of an approach that would prevent new infections. Treatment of pregnant women for their own disease is clearly important, but beyond the scope of this report. The program of interventions described here can be accomplished ethically and at a reasonable cost compared with alternative treatments. THE HIV/AIDS EPIDEMIC Since HIV/AIDS was recognized only two decades ago, the disease has reached epidemic proportions in many countries, especially in sub-Saharan

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Improving Birth Outcomes: Meeting the Challenge in the Developing World Africa (see Figure 8-1). Worldwide, approximately 3 million people died of AIDS during 2001. By the end of that year, an estimated 40 million people were living with HIV/AIDS—28 million in sub-Saharan Africa alone (Joint United Nations Programme on HIV/AIDS, 2001). In parts of southern Africa the prevalence of HIV in childbearing women may exceed 30 percent. The Joint United Nations Programme on HIV/AIDS estimates that about half of the 15-year-olds now living in the most heavily infected countries in Africa will eventually die of the disease and that it will reduce life expectancy in Southern Africa, which reached a high of 59 years in the early 1990s, to 45 years between 2005 and 2010 (Joint United Nations Programme on HIV/AIDS, 2000a, 1999). This represents a return to life expectancy rates not seen in the region since the early 1950s. HIV/AIDS is killing large numbers of men and women in developing countries at the most productive time of their lives. They include doctors, farmers, and workers in agriculture, mining, and industry who not only support their families and raise children, but who make important contributions to the social and economic welfare of their countries. The loss of many teachers profoundly affects economic productivity, as it interferes with the development of human capital. Absenteeism, decreased productivity, worker turnover, training costs, funeral and death benefits are increasing across all sectors in many African countries, draining scarce public resources and impeding job creation and foreign investment (Joint United Nations Programme on HIV/AIDS, 2001). Many parents who have died of HIV/AIDS have orphaned children, some of them infected with HIV themselves, who are typically cared for by extended families (Mukwaya, 1999). UNAIDS estimates that there have been 13.2 million AIDS orphans in the world through 2000, 12.1 million in Sub-Saharan Africa (Joint United Nations Programme on HIV/AIDS, 2000a). HIV in Women of Childbearing Age In many developing countries, a high proportion of the female population is infected with HIV as compared with the global average. In sub-Saharan Africa, where heterosexual transmission predominates, women constitute 55 percent of the adults living with HIV/AIDS. In South and Southeast Asia and the Caribbean, women make up 30 percent to 50 percent of the HIV-infected adults. By comparison, women constitute about 20 to 40 percent of HIV-infected adults in North America, Western and Central Europe, Latin America, North Africa and the Middle East. The relatively high prevalence of HIV in women of childbearing age in developing countries increases the risk of perinatal transmission (Joint United Nations Programme on HIV/AIDS, 2001; Newell, 2000). Biological and cultural factors help to explain the high prevalence of

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Improving Birth Outcomes: Meeting the Challenge in the Developing World FIGURE 8-1 Worldwide HIV prevalence rates in adults at the end of 2001. Estimates are based in large part on anonymous seroprevalence surveys of women in antenatal care. SOURCE: Joint United Nations Programme on HIV/AIDS, 2002.

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Improving Birth Outcomes: Meeting the Challenge in the Developing World HIV infection among women in the developing world. The subordinate sexual and economic status of women in many cultures contributes to the acquisition of HIV as well as of other sexually transmitted diseases, which also increase susceptibility to HIV infection (Joint United Nations Programme on HIV/AIDS, 2001). In Africa and South Asia, for instance, it is not uncommon for women to be coerced or seduced by older men into having sex. In some cultures there is a myth that if a man infected with an STD including HIV has sexual relations with a virgin, he can cure himself of his disease (Mukwaya, 1999). In some populations, especially in sub-Saharan Africa, the estimated prevalence of HIV among pregnant women reaches 36 percent (Walker et al., 2002) (see Figure 8-1). In South and Southeast Asia, the overall prevalence in childbearing women is likely to be much lower than in Africa; there, HIV prevalence rates of up to 5 percent have been documented in antenatal clinics. The effects of high HIV prevalence on child mortality can be roughly estimated as follows: if one-third of the childbearing women in a population were infected with HIV, and the risk of mother-to-child transmission was one in three (as has been documented in some developing countries), then about 10 percent of children born in that population would be infected with HIV. Because nearly all HIV-infected children will die before they reach adulthood, these deaths would therefore raise child mortality by approximately 100 per thousand live births. And since maternal mortality negatively affects children’s survival, children who were not infected at birth would still face an increased risk of death after losing their mothers to AIDS. Perinatal Transmission of HIV Transmission of HIV from mother to child can take place in utero, intrapartum, or postpartum through breastfeeding (Mofenson, 1997). In sub-Saharan Africa and other developing countries, 25 to 35 percent of children born to HIV-infected mothers become infected at birth or shortly thereafter (De Cock et al., 2000; Brocklehurst, 2002). By contrast, the transmission rate in industrialized countries has been reduced to 5 percent or less through programs of antenatal counselling, testing, and antiretroviral treatment for infected women (Mofenson and McIntyre, 2000; Coll et al., 2002). A series of maternal, obstetrical, and postpartum risk factors can affect the probability and the timing of mother-to-child transmission of HIV. The results of the European Collaborative Study demonstrated a linear relationship of transmission with decreasing maternal CD4+ cell counts, seemingly independent of other factors (European Collaborative Study, 1992). Other studies associate high maternal plasma HIV RNA levels with a significant

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Improving Birth Outcomes: Meeting the Challenge in the Developing World risk of perinatal HIV infection (Garcia et al., 1999; Mofenson et al., 1999), although transmission may occur even when the virus is undetectable. Separate studies of cohorts of pregnant women in Malawi and the United States have also found an association between low maternal vitamin A levels in pregnancy and increased risk of transmission (Semba, 1997; Greenberg et al., 1997). Other studies (Burns et al. 1999; Fawzi, 2000) did not detect such a trend, however. Several obstetric factors also influence the rate of perinatal HIV transmission. Prolonged rupture of membranes, instrumentation, vaginal delivery, and birth trauma all increase the child’s risk of infection (International Perinatal HIV Group, 2001; Mofenson, 1997). Studies in both humans and primates demonstrate the transmission of HIV through maternal blood or secretions; thus if membranes rupture prematurely or if the mother hemorrhages, the child is at increased risk for infection (Mofenson, 1997). In the postpartum period, breastfeeding is the primary mode of mother-to-child HIV transmission. A randomized trial in Nairobi, Kenya, that compared breastfeeding and formula feeding found that breastfeeding increased the risk of HIV transmission by 16.2 percent, which accounted for 44 percent of HIV infection in the breastfeeding arm of that study. Most—75 percent—of the risk difference between the two arms of the study occurred in the first 6 months, but transmission continued throughout the duration of exposure (Nduati et al., 2000). Coutsoudis and colleagues (2001) have shown that mixed infant feeding (breast milk plus other liquids) is associated with higher rates of transmission than exclusive breastfeeding. Children in developing countries who contract HIV at birth or shortly thereafter rarely live more than a few years. In several studies in Africa, the probability of death by the age of 12 months in HIV-infected children was found to be about 30 percent, and by the age of 5 years 60 to 90 percent had died (Joint United Nations Programme on HIV/AIDS Reference Group on Estimates, Modelling, and Projections, 2002; Adetunji, 2000; Tudor-Williams, 2000). A study in Malawi concluded that nearly 90 percent of African children infected with HIV do not survive beyond their third birthday (Taha et al., 2000). INTERVENTIONS TO PREVENT HIV TRANSMISSION Antiretroviral Strategies Antiretroviral drugs that have proved effective in the treatment of adults and children with AIDS when administered either individually or in combination have also been tested and compared for their ability to prevent mother-to-child transmission of HIV. These medications include zidovudine (ZDV or AZT); ZDV in combination with lamivudine (3TC); and

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Improving Birth Outcomes: Meeting the Challenge in the Developing World nevirapine (NVP) (Nolan et al., 2002). Research indicates that with appropriate antiretroviral therapy and elective cesarean delivery, perinatal HIV transmission rates can be reduced to less than 2 percent (Mandelbrot et al., 2001). Table 8-1 summarizes the conditions and results of several key trials described below, many of which were conducted in developing countries. Zidovudine (ZDV or AZT). A seminal study by the AIDS Clinical Trials Group (ACTG) in 1994 concluded that the antiretroviral drug zidovudine (ZDV), previously known to delay the progression of AIDS in persons with relatively advanced disease, was effective in reducing the risk of perinatal transmission (Connor et al., 1994). Based on these and subsequent results, the protocol used in that study—known as the ACTG 076 regimen—has become the minimum standard of care in industrialized countries (Institute of Medicine, 1999). In the United States, mother-to-child transmission of HIV has fallen by about 70 percent from its peak in the early 1990s (Centers for Disease Control and Prevention, 1999). However, while the ACTG 076 regimen is considered cost-effective in the industrialized world, it is considered too expensive and logistically difficult to establish in most developing countries. As an alternative to the ACTG 076 regimen, a series of clinical trials of a shorter course of ZDV, which includes daily doses of the drug beginning late in pregnancy, have been carried out in Southeast Asia and sub-Saharan Africa. One of two short-course ZDV trials that have been conducted in Thailand, the Bangkok trial, found that a short-course regimen reduced mother-to-child HIV transmission by 50 percent, at a cost of about $200 to $400 per person (Shaffer et al., 1999; Mofenson and McIntyre, 2000). A follow-up study found that 81 percent of the children who received ZDV had no significant adverse events associated with treatment by 18 months (Chotpitayasunondh et al., 2001). The second Thai study, the Perinatal HIV Prevention Trial (PHPT), compared several different ZDV regimens using the same doses as one of the regiments in the Bangkok trial. A short prenatal/short postnatal arm of the trial was stopped early because the transmission rate was significantly higher than in the long prenatal/long postnatal arm. At 18 months, the transmission rate was found to be significantly lower in the long prenatal treatment arms (Lallemant et al., 2000; Mofenson and McIntyre, 2000). Both African ZDV studies, which took place in Ivory Coast and Burkina Faso, were placebo-controlled trials in which the mothers breastfed. The Ivory Coast trial yielded a 37 percent reduction in the rate of transmission (Wiktor et al., 1999), while the DITRAME ANRS 049 study, conducted in Ivory Coast and Burkina Faso reported a 38 percent reduction in transmission (Dabis et al., 1999). A recent Cochrane Review (Brocklehurst and Volmink, 2002) concluded that the effectiveness of zidovudine therapy from 28 weeks in preg-

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Improving Birth Outcomes: Meeting the Challenge in the Developing World nancy for the mother through 3 days for the infant (the long-short term course) and from 35 weeks in pregnancy for the mother to 6 weeks for the infant (the short-long term course) provided the same protection as the long-long course. Combination therapy. With the advent of two- and three-drug combinations to reduce viral loads in people with AIDS, researchers began to evaluate benefits of combining ZDV with other antiretroviral agents to prevent perinatal HIV transmission. Mandelbrot and colleagues (2001) found, using retrospective controls, that a combination of ZDV and lamivudine (3TC) reduced the risk of HIV transmission by almost 80 percent in non-breastfeeding women compared with women taking only ZDV. However, concerns about possible side effects (see toxicity discussion below) and the fact that current treatment guidelines typically call for a three-drug regimen that includes a costly protease inhibitor limit the practical impact of this finding. The PETRA trial in South Africa, Uganda, and Tanzania tested less intensive ZDV plus 3TC regimes than those used by Mandelbrot and colleagues (2001), and did so in women who mostly breastfed their infants (Petra Study Team, 2002). The study compared a three-part regimen (prepartum, intrapartum, and postpartum) to a combination of intrapartum and postpartum therapy and intrapartum therapy only. At 6 weeks postpartum, the rate of transmission was reduced by 50 percent in the three-part treatment group; the two-part regimen achieved a 37 percent reduction; and the intrapartum-only group was not significantly different from the placebo group. At 18 months the differences between the groups were less pronounced, probably due to the effects of breastfeeding. A recent Cochrane Review (Brocklehurst and Volmink, 2002) concluded that the combination therapy using zidovudine and lamivudine (3TC) decreased the risk of transmission when the combination is given during the antenatal and intrapartum periods or the intrapartum and postpartum periods, but not when given only in the intrapartum period alone. Nevirapine. The 1999 HIVNET 012 randomized controlled trial in Uganda found that nevirapine (NVP), a nonnucleoside reverse-transcriptase inhibitor that is rapidly absorbed orally, reduced the risk of perinatal transmission by 47 percent (Guay et al., 1999). This result, which is comparable to results achieved with a short course of ZDV, followed a single intrapartum dose of NVP for the mother and a single dose for the infant after birth. That regime costs about $4—a tiny fraction of the cost of ZDV treatment (Marseille et al., 1999). The SAINT trial in South Africa compared NVP to a combination of ZDV and 3TC, both regimens administered intrapartum and postpartum. Preliminary results indicate that there was no significant difference in HIV infection in the two groups at 8 weeks postpartum (Moodley, 2000).

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Improving Birth Outcomes: Meeting the Challenge in the Developing World TABLE 8-1 Trials of Antiretroviral Treatments to Prevent Mother-to-Child HIV Transmission Study Name and Reference Population Characteristics Treatment (Pre- and Intrapartum to Mother, Postpartum to Child) ACTG 076 (Connor et al., 1994) Nonbreastfeeding women in US and France Pre: 100 mg ZDV orally 5x daily starting at 14-34 weeks gestation Intra: 2 mg/kg ZDV IV for 1 hour, then 1 mg/kg ZDV IV per hour until delivery Post: 2 mg/kg orally 4x daily for 6 weeks Bangkok trial (Shaffer et al., 1999) Nonbreastfeeding women in Thailand Pre: 300 mg ZDV orally 2x daily starting in 36th week of pregnancy Intra: 300 mg ZDV every 3 hours Perinatal HIV Prevention Trial (PHPT) (Lallemant et al., 2000) Nonbreastfeeding women in Thailand Short Pre: 300 mg ZDV orally 2x daily starting at 35 weeks gestation Intra: 300 mg ZDV every 3 hours Short Post: 2 mg/kg ZDV orally every 6 hours for 3 days   Long Pre: 300 mg ZDV orally 2x daily starting at 28 weeks gestation Intra: 300 mg ZDV every 3 hours Short Post: 2 mg/kg ZDV orally every 6 hours for 3 days Short Pre: 300 mg ZDV orally 2x daily starting at 35 weeks gestation Intra: 300 mg ZDV every 3 hours Long Post: 2 mg/kg ZDV orally every 6 hours for 6 weeks Long Pre: 300 mg ZDV orally 2x daily starting at 28 weeks gestation Intra: 300 mg ZDV every 3 hours Long Post: 2 mg/kg ZDV orally every 6 hours for 6 weeks RETROCI (Wiktor et al., 1999) Breastfeeding women in Ivory Coast Pre: 300 mg ZDV orally 2x daily starting at 36 weeks gestation Intra: 300 mg ZDV every 3 hours DITRAME ANRS 049 (Dabis et al., 1999) Mostly breastfeeding women in Ivory Coast and Burkina Faso Pre: 300 mg ZDV orally 2x daily starting at 36-38 weeks gestation Intra: 600 mg ZDV at onset of labor Post (maternal): 300 mg ZDV orally 2x daily for 1 week

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Improving Birth Outcomes: Meeting the Challenge in the Developing World   Risk of Transmission (% of Children)   HIV Status Evaluated Control Treatment Relative Reduction in Risk (in %) 18 mo. 25.5 8.3 67 6 mo. 18.9 9.4 50.0 6 mo. — 10.5 Stopped early 18 mo. — 4.7 In utero transmission higher with short maternal treatment   — 8.6     — 6.5   3 mo. 24.9 26.1 15.7 16.5 37 37 6 mo. 27.5 18.0 35

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Improving Birth Outcomes: Meeting the Challenge in the Developing World     Treatment (Pre- and Intrapartum to Mother, Postpartum to Child) Study Name and Reference Population Characteristics   RETROCI and DITRAME pooled analysis (Peiperl, 2001)   As above         Nonbreastfeeding women in France ACTG 076 regimen (historical controls)   ACTG 076 regimen plus 150 mg 3TC orally 2x daily starting at 32 weeks gestation and 2 mg/kg orally 2x daily for 6 weeks to child PETRA (Petra Study Team, 1999) Mostly breastfeeding women in South Africa, Tanzania, and Uganda Intra: 300 mg ZDV every 3 hours and 150 mg 3TC orally every 12 hours   Intra: as above Post (maternal): 300 mg ZDV and 150 mg 3TC orally 2x daily for 1 week Pre: 300 mg ZDV and 150 mg 3TC orally 2x daily starting at 36 weeks gestation Intra: as above Post (maternal): as above Intra: 300 mg ZDV every 3 hours and 150 mg 3TC orally every 12 hours Intra: as above Post (maternal): 300 mg ZDV and 150 mg 3TC orally 2x daily for 1 week Pre: 300 mg ZDV and 150 mg 3TC orally 2x daily starting at 36 weeks gestation Intra: as above Post (maternal): as above

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Improving Birth Outcomes: Meeting the Challenge in the Developing World sidered implementing such programs but have declined to do so, citing their cost as well as social, cultural, and ethical concerns. Cost. The cost of treating individuals with HIV may exceed a developing country’s national health budget on a per capita basis. In sub-Saharan Africa, for instance, the annual budget for health care averages $24 per capita (World Bank, 1993). Antenatal screening and treatment with NVP costs less than $10 per pregnant woman, most of which pays for counseling and HIV testing; however, only pregnant women (not the whole population) incur costs. A more relevant comparison, therefore, might be made with antenatal and delivery care, which typically costs $90 per woman in the poorest developing countries (World Bank, 1993); that figure would increase by less than 10 percent were it to include the cost of HIV screening. Social, cultural, and ethical concerns. In light of the evidence that a program of antenatal HIV screening and prophylaxis of infected mothers to prevent transmission is both effective and cost-efficient under most if not all circumstances, one might argue that not to implement antenatal HIV screening is unethical. However, acceptability of HIV counseling and testing has limited implementation for treatment programs in some settings (Meda et al., 2002). If stigma and discrimination associated with HIV infection is high—if women who are known to have AIDS or HIV infection endure beatings and may be disowned by their families (Berer, 1999; Mukwaya, 1999)—it is understandable that women might want to avoid HIV testing, especially during pregnancy, a time of great vulnerability. Concerns about stigma and discrimination also interfere with women’s ability to accept antiviral treatment for themselves and bottle-feeding for their infants. A study in Rwanda suggested that women 35 years and older and those whose partners had skilled and well-paid jobs were more likely to accept HIV testing (Kowalczyk et al., 2002). Clearly, the stigma associated with HIV status must be removed through extensive social programs if efforts to prevent transmission are to succeed, but such changes will take time. Women must meanwhile be counseled frankly about the costs and benefits of HIV testing and treatment if necessary for themselves and their children and be allowed to make their own decisions. Policy makers in developing countries have also questioned the appropriateness of treating women to prevent transmission of HIV at birth if (a) there is a high risk of transmission later through breastfeeding and (b) parents are likely to die of HIV disease before the infant reaches adulthood. Many observers believe that a life is worth saving whatever the risks that the child faces later in life, and that antenatal HIV screening with prophylaxis offers many children a chance to live into adulthood. Moreover, it can be argued that the main risks facing children saved from HIV infection can themselves be mitigated. The risk of transmission through breastfeeding can be eliminated or reduced through the provision of alter-

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Improving Birth Outcomes: Meeting the Challenge in the Developing World natives such as formula, and most AIDS orphans can be raised by extended families, as they are today in many developing countries. Children saved from HIV infection through antenatal screening programs may represent a burden on society and especially their relatives during early life, but they have the potential to contribute significantly to society and the economy, as well as to the welfare of their extended families. If resources are not sufficient to provide treatment to all HIV-infected citizens, treatment of pregnant women should be considered seriously in setting priorities, because of transmission from mother to baby. One might also ask whether it is ethically appropriate to treat a mother with a short course or a single dose of drugs that would benefit her child, but not the mother herself. Many observers have argued that it is, given the inability of many developing countries to pay for lifelong therapy for people with HIV, the tangible benefits to the child, and the satisfaction that many women get from selflessly protecting their children. Prophylaxis of pregnant women also can be distinguished from other treatment programs in that it aims to prevent new AIDS cases, and is far more effective in doing so than other measures. In the United States, where HIV prevalence rates in childbearing women are low and many women are well informed about HIV and AIDS, the Institute of Medicine has recommended that prenatal care for all women include HIV testing, with notification of results to the patient (Institute of Medicine, 1999). In developing countries, where women might be less aware of HIV/AIDS, for example among women in India (Chaterjee, 1999), and where prevalence rates may be higher, counseling and informed consent for HIV testing in antenatal care should be more intensive and focused on helping women make informed choices for themselves. Guidelines for Antenatal HIV Screening A recent summary of the characteristics of a well-organized perinatal public health screening program (Institute of Medicine, 1999), which draws upon earlier principles developed by WHO (Wilson and Jungner, 1968), is relevant to countries considering antenatal HIV screening programs: The goals of a screening program must be clearly specified and achievable. The natural history of the condition should be adequately understood, treatment for those found positive must be widely accepted by the medical community, and there should be evidence that early intervention improves health outcomes. The screen should be able to distinguish individuals likely to have the condition from those not likely to have it.

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Improving Birth Outcomes: Meeting the Challenge in the Developing World There must be adequate resources to diagnose and treat every person with the condition. The test and intervention should be acceptable to the affected population. Given the evidence discussed in this chapter, and understanding “treatment” as short-course ZDV or intrapartum NVP intended to prevent transmission to the infant, antenatal HIV screening programs would likely be judged to be ethically appropriate in most developing countries where the prevalence of HIV in childbearing mothers is high and where resources exist to treat them. RECOMMENDATIONS Antenatal screening and prophylaxis programs represent the most immediate means to reducing perinatal HIV transmission. The reduced cost of drug therapy makes them more comparable with other health and economic investments. The most significant cost is, however, that associated with building the health care infrastructure needed to deliver testing, counselling, and drugs.When the social costs of AIDS are considered, especially in populations with a high prevalence of HIV1 in childbearing women, antenatal screening programs in developing countries appear to be cost-saving; in populations with low prevalence rates, the per capita cost can be low. In order to implement antenatal HIV screening programs as quickly as possible, international support should be organized to supplement limited resources of developing countries. The social cost of HIV/AIDS is very high in terms of the stigma and discrimination borne by women who test positive, especially those who have little power. Fear of the consequences of a positive test and the lack of resources to treat HIV infection in developing countries turn women away from testing. In addition, relatively few women in developing countries realize that HIV can be transmitted to their children, or that effective measures to reduce the risk of transmission are available. Thus education regarding the risks and benefits of antenatal HIV screening and treatment must be incorporated into antenatal care along with options for HIV screening and antiretroviral prophylaxis. There are inadequate data on which to base specific recommendations on breastfeeding or formula feeding by HIV-infected women in developing countries. Although formula feeding eliminates the risk of vertical trans- 1   HIV is generally considered to be a public health problem in populations where the seroprevalence is above 1 percent.

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Improving Birth Outcomes: Meeting the Challenge in the Developing World mission of HIV, the use of unsafe water to reconstitute infant formula poses an even greater hazard to neonates in most settings. Accordingly, the benefits and disadvantages of breast and formula feeding need to be assessed simultaneously, and HIV-infected women should receive counseling on infant feeding options appropriate to the woman’s cultural, social, and economic circumstances and support for her individual choice. Recommendation 4. The following strategy is recommended for incorporation into preconceptional and antenatal care in all settings: In areas where HIV is a public health problem (seroprevalence exceeds 1 percent), antenatal screening for HIV should be provided to women who, after counseling, give their informed consent. Women who test positive should receive antiretroviral prophylaxis to prevent mother-to-child transmission of the virus, along with appropriate counseling on infant feeding options. (See Chapters 2, 3, 6, and 7 for other components of this recommendation.) The success of programs to prevent perinatal HIV transmission—and indeed of all efforts to reduce the global impact of AIDS—rests on the longer-term prospect of removing the stigma associated with the disease. Countries should use every means possible to reduce this stigma, which presents a major barrier to the prevention and treatment of HIV/AIDS. It is possible that incorporating HIV screening as a routine part of antenatal care for all women will contribute to that goal. RESEARCH NEEDS Despite considerable progress over the last decade, optimizing the prevention of perinatal HIV infection, especially in low-resource settings, will require ongoing study. The committee therefore recommends research on the following topics to support the previous recommendation. Identifying effective and efficient ways to implement antenatal HIV screening programs in developing country settings. Discovering effective counseling techniques that increase women’s awareness of the risks and benefits of antenatal HIV screening and encourage them to make informed choices regarding testing. Identifying barriers to women accepting HIV testing and discovering means to overcome them. Developing and testing rapid HIV diagnostic tests suitable for field settings to be used late in pregnancy or in the intrapartum period.

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Improving Birth Outcomes: Meeting the Challenge in the Developing World Selecting the most effective antiretroviral drugs, doses, and regimens for reducing perinatal HIV transmission, and determining the extent to which the effectiveness of treatments can be preserved while reducing duration of therapy, drug dose, and cost. Identifying effective alternatives to antiretroviral medications for reducing the risk of transmission from mother to child, especially during breast feeding. Finding effective ways to reduce the stigma associated with AIDS. CONCLUSION Preventing perinatal HIV transmission will not substantially reduce mortality in the target populations served by this study (mothers, fetuses, and neonates). However, as the swiftest and most affordable means of reducing the number of new AIDS cases in developing countries, prevention of mother-to-child infection represents a key opportunity for antenatal care in developing countries. Because stigma and discrimination associated with HIV infection may pose a considerable barrier to diagnosis, successful programs to prevent perinatal transmission will need to educate pregnant women about the risks and benefits of antenatal HIV screening and prophylaxis. Clearly, the most reliable means of preventing perinatal HIV transmission is to prevent infection among women of childbearing age. Achieving this long-term objective will require the implementation of primary prevention strategies, as well as the education and empowerment of women. For the near term, the evidence and analyses reviewed in this chapter demonstrate that the goal of preventing HIV infection in substantial numbers of children born to infected women in developing countries is well within reach. REFERENCES Adetunji J. 2000. Trends in under-5 mortality rates and the HIV/AIDS epidemic. Bulletin of the World Health Organization 78(10):1200–1206. Arifeen S, Black RE, Antelman G, Baqui A, Caulfield L, Becker S. 2001. Exclusive breastfeeding reduces acute respiratory infecton and diarrhea deaths among infants in Dhaka slums. Pediatrics 108(4):E67. Ashraf RN, Jalil F, Zaman S, Karlberg J, Khan SR, Lindblad BS, Hanson LA. 1991. Breast feeding and protection against neonatal sepsis in a high risk population. Archives of Diesase in Childhood 66(4):499–490. Berer M. 1999. Reducing perinatal HIV transmission in developing countries through antenatal and delivery care, and breastfeeding: supporting infant survival by supporting women’s survival. Bulletin of the World Health Organization 77(11):871–877. Blanche S, Tardieu M, Rustin P. 1999. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues, Lancet 354(9184):1084–1089.

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