In a recent issue of AIDS, the Zvitambo study group from Zimbabwe showed increased postpartum mortality among HIV-infected women with a high CD4 cell count who were not eligible for and not receiving antiretroviral therapy (ART), compared to HIV-uninfected postpartum women from the same population . In the 2 years postpartum, the adjusted mortality hazard ratio (95% confidence interval) was 7.3 (3.6–15.1) among HIV-infected women with baseline CD4 cell count between 600 and 800 cells/ml, compared to the reference category of HIV-uninfected women . The authors therefore argued the case for early ART initiation among all pregnant and postpartum women in Africa, irrespective of CD4 cell count or treatment eligibility. We entirely agree with this interpretation of their findings, in particular because such a strategy would also contribute to the elimination of paediatric HIV in breastfeeding populations.
To prove this point, we combined data from two cohorts in south  and west Africa  to evaluate mother-to-child transmission (MTCT) risk through breastfeeding . Similar to the Zvitambo trial, maternal ART was unavailable at the time of the study in these two populations. In this pooled analysis, breastfeeding duration was a median of 6.4 months (interquartile range: 4.4–12.4), shorter than usually observed in African settings; postnatal transmission rates were, thus, similarly lower than seen elsewhere. Overall, 70% of these HIV-infected pregnant breastfeeding women had CD4 cell counts above 350 cells/ml (Table 1) and would, therefore, not have been eligible for ART for their own health according to the most recently agreed international recommendations . In the absence of ART intervention, the cumulative risk of HIV transmission through breastfeeding in the first 18 months of life was substantial in this group (4.8%), despite their high CD4 cell count, accounting for 53% of all cases of breastfeeding transmission (the remaining 47% of postnatal transmission cases occurred among women with <350 CD4 cells/ml). Further, even women with baseline CD4 cell counts above 500 or above 700 cells/ml were at substantial risk of postnatal transmission (Table 1). These findings highlight the crucial need for an antiretroviral based intervention also among women with higher CD4 cell counts, so that the risk of HIV transmission can be significantly reduced for all HIV-exposed infants. If ART had been provided to these women with CD4 cell counts over 350, the expected MTCT rate would have been at least halved, as per European experience .
In the recently released WHO guidelines on the use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants, two options of similar efficacy are offered for women with CD4 cell count above the 350 CD4 treatment eligibility threshold . Option A consists in providing maternal zidovudine prophylaxis from the second trimester of pregnancy until delivery, followed by daily oral nevirapine to the breastfed infant until all breastfeeding has ceased. Option B consists of the provision of maternal triple antiretroviral prophylaxis (as per ART for treatment) starting from the second trimester of pregnancy until all exposure to breast milk has ended.
The new results from the Zvitambo study clearly support the initiation of triple antiretroviral prophylaxis among all pregnant women and continued throughout breastfeeding exposure, following option B, not only to prevent mother-to-child HIV transmission and enable safer breastfeeding practices, but importantly also to improve maternal health. Both eligible and ineligible women would then be receiving the same triple antiretroviral regimen, which would make this universal strategy easier to implement at a population level . However, in a context wherein all pregnant women would be offered triple antiretroviral regimens, the question of whether and when to stop this intervention in women who are not eligible for ARV treatment according to the current international guidelines is of particular interest. The risk for maternal health of stopping maternal triple ARV prophylaxis after breastfeeding cessation among women with high CD4 cell count is unknown. Hence, this strategy would need to be assessed in carefully conducted field studies in terms of acceptability, efficiency and maternal and infant safety.
The present study is sponsored by ANRS, Paris, France; SIDACTION, Paris, France and Wellcome Trust, London, UK.
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