Prevention of mother-to-child transmission of HIV-1 by antiretroviral treatment and the impact on maternal health in Dar es Salaam, Tanzania

Abstract: This thesis describes the results of the Mitra Plus study, including the outcome of antiretroviral therapy (ART) for preventing mother-to-child transmission (PMTCT) of HIV-1 in breastfeeding women and improving HIV- free survival (Paper I), treatment outcome of women initiated on ART for life (Paper II) and reasons for poor drug adherence (Paper III) in Dar es Salaam, Tanzania. Another study (qualitative in nature) explored women’s preferred treatment option for the prevention of breast milk transmission of HIV (Paper IV). In the Mitra Plus study, 501 HIV-1 infected pregnant women were treated with Zidovudine + Lamivudine + Nevirapine /Nelfinavir from 34 weeks of gestation. Treatment of mothers was stopped at six months post-delivery except for those who needed ART for their own health (CD4 cell count = 200/µL or WHO stage III or IV). Mothers were advised to exclusively breastfeed and to wean abruptly when the infant was between five and six months. The cumulative HIV-1 rates determined by Kaplan Meier survival analysis of transmission of 441 infants were 4.1% (95% confidence intervals (CI) 2.2-6.0%) at six weeks, 5.0% (95% CI 2.9-7.1%) at six months and 6.0% (95% CI 3.7-8.3%) at 18 months post-delivery. The cumulative risk of HIV transmission between six weeks and six months was 1.0% and between six months and 18 months was 1.1%. The cumulative HIV infection or death rate was 13.6% (95% CI 10.3-16.9%) at 18 months after delivery. Thus extended maternal prophylaxis with ART resulted in low HIV-1 transmission during breastfeeding and a high HIV-free child survival at 18 months. Follow-up of the Mitra Plus women on ART for life revealed that, following an initial treatment success at three and six months, virologic and immunologic failure were common at 12 and 24 months postpartum. A high proportion of viremic mothers also had drug resistance mutations. The mortality rate was fairly low, 5.9% (95% CI 2.5-13.7%). The probability of virologic and immunologic failure was associated with reported non-perfect adherence to ART at month 24 postpartum. In-depth interviews revealed that women’s main motivation for ART adherence was to protect the infant from HIV infection. HIV-related stigma, poverty and overwhelming daily demands were other important barriers to ART adherence. Among the currently recommended WHO Options for preventing breast milk transmission (Ainfant prophylaxis, B- maternal prophylaxis and B+- maternal treatment for life) women preferred Option B as they thought it was better than Option A because of less risk for HIVassociated stigma, less drug side effects for the child and better logistics for postnatal adherence. Women were not in favour of Option B+ as they anticipated loss of motivation after protecting the child, fearing drug side effects and many did not feel ready to embark on lifelong medication when asymptomatic regardless of CD4 count. In conclusion, women should be counselled about the possibility to “opt-out” of ART after cessation of breastfeeding. Drug adherence counselling, drug safety and benefits, economic concerns and available resources for laboratory monitoring and evaluation should be addressed during B+ implementation to enhance long-term feasibility and effectiveness.