Postnatal Human Immunodeficiency Virus-1 Transmission After Cessation of Infant Extended Antiretroviral Prophylaxis and Effect of Maternal Highly Active Antiretroviral Therapy

Abstract

A randomized clinical trial, the PostExposure Prophylaxis of Infants trial in Blantyre, Malawi, (PEPI-Malawi), which was carried out in a resource-limited setting showed that antiretroviral prophylaxis (nevirapine alone or nevirapine plus zidovu- dine) extended to age 14 weeks in infants who were breast-fed by human immunodeficiency virus (HIV)-infected mothers, reduced the risk of HIV-1 infection by 67%. In a similar setting, use of maternal highly active antiretroviral therapy (HAART) has also reduced postnatal HIV transmission; its efficacy, however, has not been confirmed in a randomized trial. The availability of antiretroviral therapy in 2006 provided the opportunity to evaluate, in the PEPI-Malawi trial, the complementary effects of infant prophylaxis and maternal HAART in reducing transmission of HIV through breast milk. This follow-up observational study determined the incidence of HIV infection and the association between postnatal HIV transmission and maternal HAART among breast-fed infants born to HIV-1-infected women in the PEPI-Malawi trial who were HIV negative after 14 weeks of extended antiretroviral prophylaxis. The infants were randomized at birth to receive either oral single-dose nevirapine plus 1 week of zidovudine (control), control plus nevirapine daily to age 14 weeks, or control followed by nevirapine plus zidovudine daily to age 14 weeks. Three maternal exposure categories were examined as follows: The HAART-eligible/untreated category consisted of infants whose mothers were eligible (defined as CD4 cell count <250 cells/μL) but had not received HAART. The HAART eligible/treated category included infants with eligible mothers who had started to receive HAART. The HAART-ineligible category was comprised of infants whose mothers were ineligible for HAART because all prior CD4 cell counts were ≥250 cells/μL. Of the 2318 infants in the study, 130 (5.6%) acquired an HIV infection; a total of 310 of their mothers (13.4%) received HAART. The postnatal transmission rates (cases per 100 person-years) were as follows: HAART eligible, untreated (10.56, with a 95% confidence interval [CI] of 7.91-13.82); HAART eligible, treated (1.79, with a 95% CI of 0.58-4.18); and HAART ineligible (3.66 with a 95% CI of 2.86-4.61). The use of postpartum HAART in women with low CD4 cell counts was associated with an 82% reduction in postnatal HIV transmission, compared to those with similar low CD4 cell counts who had not been given HAART (hazard ratio, 0.18; 95% CI, 0.07-0.44). These findings suggest that there are 2 options for preventing viral transmission from HIV-infected mothers who breast-feed their infants: (1) Continue extended infant prophylaxis beyond 14 weeks with an expected protective effectiveness of 67%, or (2) administer maternal HAART with an expected protective effectiveness of 82%.