PREVENTION OF HIV INFECTION IN CHILDREN

Pediatic HIV infection has emerged as an important public health problem in industrialized and developing nations. The first children with AIDS were described in 1983. 104 Less than 2 decades later, the global HIV epidemic is having a profound effect on the health and survival of children. Almost all HIV infections among young children are caused by mother-to-child transmission (MCT). In the absence of antiretroviral prophylaxis, the risk for transmission from HIV-1–infected mothers to their infants is 15% to 45%, with the highest rates reported in sub-Saharan Africa. 136 In contrast, the rate of MCT of HIV-2 is approximately 1%. 1 Postnatal transmission through breast-feeding is estimated to contribute one third to half of HIV-1 infections in children worldwide. 65 In the United States, an estimated 15,000 HIV-infected children were born to HIV-positive women by the end of 1993, 36 and AIDS had developed in 6600 children by the end of 1995. 22 The HIV infection outcome of a previous child does not seem to affect an infected woman's risk for transmitting HIV to subsequent children. 91 The World Health Organization reports that MCT accounts for more than 1.5 million HIV-infected children worldwide and that pediatric AIDS will lead to a significant decrease in child survival rates in much of sub-Saharan Africa. 81 During the next decade, the World Health Organization estimates that 5 to 10 million children will become infected with HIV through MCT (Global Strategies Conference for the Prevention of HIV Transmission from Mothers to Infants, Washington, DC, September 1997; and Montreal, Canada, September 1999). Major advances in the understanding of the timing and pathogenesis of perinatal HIV infection have occurred in recent years, raising new hope for the prevention of perinatally acquired HIV infections. These advances and the epidemiologic risk factors for MCT have been reviewed in several articles. 13,18,50,63,66,85,92,98 The most dramatic prevention breakthrough occurred in February 1994, when the results of Pediatric AIDS Clinical Trials Group (PACTG) protocol 076 demonstrated that the risk for MCT could be decreased from 25.5% to 8.3% by treating mothers and neonates with zidovudine (ZDV). 31 The US Public Health Service (PHS) issued guidelines for the use of ZDV to reduce perinatal transmission in August 1994 and, in July 1995, universal HIV counseling and voluntary testing of pregnant women. 24,25 With the widespread adoption of these guidelines in the United States and several other industrialized countries, perinatal transmission rates have decreased substantially. Despite the effectiveness of such prevention efforts, the continued incidence of perinatally acquired AIDS among infants in the United States demonstrates ongoing perinatal transmission and underscores the need for strategies to ensure that women receive adequate prenatal care, timely HIV counseling, voluntary testing, and chemoprophylaxis to reduce perinatal transmission and avoid breast-feeding. 26 In addition, by the end of this century, an estimated 80,000 children and adolescents in the United States will be orphaned by parental death caused by HIV infection. 3 Prevention efforts need to focus on increasing access to care and providing prevention services to minority and underserved populations, among which rates of AIDS remain the highest. 61,138 Most HIV-infected children are born in the developing world, and a crucial challenge is to identify safe and effective interventions that are feasible in countries with the most significant HIV burden. Because of its high complexity and cost, the 076 regimen has not been implemented in most developing countries. Several short and simplified ZDV regimens are under investigation in Africa and Asia, and results from three of these clinical trials have been published (Table 1). 35,108,134 In Bangkok, Thailand, a short course of twice-daily oral (po) ZDV given beginning at 36 weeks of gestation and during labor to non–breast-feeding women decreased the risk for MCT by half compared with placebo. 108 Slightly less treatment efficacy was observed among breast-feeding populations in two clinical trials, one in Ivory Coast and one in Ivory Coast/Burkina Faso (37% MCT reduction by 3 mo of age and 38% by 6 mo of age, respectively). 35,134 Rapid translation of these important clinical trial findings into public health policy and practice in resource-poor settings remains a priority. 39 Widespread implementation of a short-course prophylactic ZDV or other antiretroviral drug regimens in the developing world, where most women present late for prenatal care, have limited access to HIV testing and counseling, and depend on breast-feeding to protect infants from early mortality, provides a formidable challenge and a unique opportunity to protect future generations of children from the burden of HIV.