In a resource-constrained, programmatic setting, we found that maternal HAART was associated with a substantial decrease in the rate of mother-to-child transmission compared with zidovudine. Mothers who took antenatal HAART had considerably lower CD4 cell counts, a factor strongly associated with MTCT,15
but were still less likely to transmit HIV. Infants born to mothers receiving HAART experienced greater HIV-free survival than infants whose mothers took zidovudine.
Women in this study initiated antiretroviral therapy under routine programmatic conditions without expanded access to viral load testing, specialist care, or adherence support present in many clinical trials. However, the observed MTCT rate in the HAART group is among the lowest reported in the literature3, 5-8, 16
, supporting the effectiveness of HAART for the prevention of MTCT outside the context of a clinical trial.
Our findings do not support the equivalence of zidovudine and HAART for prevention of MTCT. More than half of all infant HIV infections in the zidovudine group came from women with CD4 cell counts ≥ 350 cells/μL. The MTCT rate in this group was significantly higher than in the group of women with much lower CD4 cell counts, and consequently at greater risk,15
who received antenatal HAART. While shorter duration of antenatal antiretroviral treatment for women on zidovudine may have contributed to increased risk compared with HAART, this effect is unlikely to be substantial. Late antiretroviral initiation was associated with increased risk of MTCT, but was similarly common in both groups. In addition, extending zidovudine monotherapy beyond 4-6 weeks does not appear to lead to further reductions in HIV viral load17, 18
or the proportion of women with an undetectable viral load at delivery,12
important predictors of MTCT risk.2, 3
This cohort provides insight to some implementation challenges. While we noted possible programmatic improvements from a prior study,19
delays in CD4 testing and HAART initiation contributed to 9 women (8.3%) eligible for HAART not starting prior to delivery, including one who transmitted HIV to her infant. Of women not on HAART at conception, 44 (15.5%) were not CD4 tested in the 6 months prior to delivery. We also observed the difficulty of delivering sdNVP to the relatively small group of mothers receiving < 4 weeks of zidovudine— only 5 (22.7%) eligible women received sdNVP. Prematurity, rather than delayed initiation, was the principal reason in both groups for decreased duration of antenatal antiretroviral therapy. Finally, nearly one-third of neonates in this cohort were premature or low birth weight, emphasizing the importance of improving access to neonatal services in parallel with programs to prevent MTCT.
In contrast with prior studies of programmatic effectiveness that have relied on the results on the subset of infants presenting for testing,4, 20-22
the prospective determination of HIV status in this study should reduce the possibility of bias. However, the analysis is subject to several limitations. We were unable to determine the HIV status for 13 infants (3.0%), including 9 who died prior to testing (none of an apparent AIDS illness), and consequently may have missed some infant HIV infections. Few women elected to breastfeed, so we cannot assess the effectiveness of HAART for prevention of breast milk transmission. With only one transmission in the HAART group, we were unable to construct a reliable multivariate model to adjust for baseline differences in maternal and infant characteristics. While many of these differences would be expected to decrease the apparent effectiveness of HAART, the non-randomized design and earlier initiation of HAART limits a conclusive assessment of HAART versus zidovudine.
In summary, we have shown that HAART initiated in a programmatic setting without frequent viral load monitoring or specialized care is highly effective at preventing MTCT. Use of antenatal HAART was associated with substantial decreased risk of MTCT compared with zidovudine (with or without sdNVP). The findings of this study indicate that a strategy to provide HAART for all HIV-infected women, as is currently being piloted in Botswana, could nearly eliminate infant HIV infection.