Prevention of mother-to-child transmission of HIV-1 through

Infant feeding

Prevention of mother-to-child transmission of HIV-1 through breastfeeding by treating mothers with triple antiretroviral therapy in Dar es Salaam, Tanzania: the Mitra Plus study.

The main aim of this study was to reduce breast-milk transmission of HIV-1 by treating HIV-1-infected women with antiretroviral therapy (ART) during breastfeeding. Mitra Plus was an open-label, nonrandomized, prospective cohort study. HIV-1-infected pregnant women in Dar es Salaam were treated with zidovudine (ZDV) + lamivudine (3TC) + nevirapine (NVP). NVP was later replaced by nelfinavir for mothers with CD4 cell counts >200 cells per microlitre or with adverse reaction to NVP. Antiretroviral therapy was initiated at 34 weeks of gestation. For women with symptomatic HIV infection or CD4 cell counts below 200 cells per microlitre, antiretroviral therapy was started earlier if possible. Treatment of the mothers was stopped at 6 months except for those mothers who needed antiretroviral therapy for their own health. The infants received ZDV + 3TC for 1 week after birth. Mothers were advised to exclusively breastfeed and to wean abruptly between 5 and 6 months. Transmission of HIV-1 was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breastfeeding population of the Petra trial arm A. There were 441 infants included in the analysis of HIV-1 transmission. The cumulative transmission of HIV-1 was4.1 % [95% confidence interval (CI): 2.2 to 6.0] at 6 weeks, 5.0% (95% CI: 2.9 to 7.1) at 6 months, and 6.0% (95% CI: 3.7 to 8.3) at 18 months after delivery. The cumulative risk of HIV transmission between 6 weeks and 6 months was 1.0% and between 6 months and 18 months 1.1%. The cumulative HIV infection or death rate was 8.6% (95% CI: 6.0 to 11.2) at 6 months and 13.6% (95% CI: 10.3 to 16.9) at 18 months after delivery. Viral load at enrolment and duration of antiretroviral therapy before delivery were significantly associated with transmission but CD4 cell count at enrolment was not. The median time of breastfeeding was 24 weeks. The transmission in the Mitra Plus study was about half of the transmission in the breastfeeding population in the Petra trial arm A at 6 months after delivery (adjusted relative hazard = 0.49, P <>The combined outcome HIV infection or death was significantly lower in the Mitra Plus study than in the breastfeeding population in the Petra trialarm A at 18 months (adjusted relative hazard = 0.61, P = 0.007). NVP-related mucocutaneous rash was demonstrated in 6.5% of 429 NVP-exposed women. The incidence of NVP-related grade 3 or 4 hepatotoxicity was low (0.5%). Antiretroviral therapy given to HIV-infected mothers in late pregnancy and during breastfeeding resulted in a low postnatal HIV transmission similar to that previously demonstrated in the Mitra study in Dar es Salaam using infant prophylaxis with 3TC during breastfeeding. The extended maternal prophylaxis with antiretroviral therapy for prevention of mother-to-child transmission of HIV-1 for breastfeeding mothers who do not need antiretroviral therapy for their own health should be further evaluated and compared with the use of infant postnatal antiretroviral prophylaxis regarding safety and cost-effectiveness.

These Mitra Plus study findings from Tanzania of low HIV transmission through breastfeeding when mothers receive antiretroviral treatment, whether they need it for their own health or not, may well have informed the new WHO ‘rapid advice’ documents released last week. Although the option remains (Option A) to provide AZT only from as early as 14 weeks of pregnancy, followed by AZT and 3TC during labour and delivery and for 7 days postpartum - with breastfeeding babies then receiving nevirapine until one week after all exposure to breast milk has ended – a new option called Option B has emerged. It includes maternal triple antiretroviral prophylaxis from as early as 14 weeks and continuing until 1 week after all exposure of the infant to breast milk ends. Changes such as these will bring us closer to the goal of virtually eliminating mother-to-child transmission of HIV.