Lopinavir-ritonavir prophylaxis not superior to lamivudine in preventing HIV in breastfeeding infants [ANRS 12174 trial]

1. This randomized controlled trial showed that prophylaxis with lopinavir-ritonavir was not superior to lamivudine in preventing HIV infections through breastfeeding for up to 50 weeks in infants born to HIV-infected mothers.

2. Both lopinavir-ritonavir and lamivudine resulted in very low rates of HIV infections.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Methods to prevent the transmission of HIV through breastfeeding, including maternal antiretroviral therapy and infant antiretroviral pre-exposure prophylaxis, have been shown to be effective. However, no trials have assessed their effectiveness for more than 6 months of breastfeeding, although breastfeeding is recommended for 12 months after birth. This study compared the safety and efficacy of administering lopinavir-ritonavir, a protease inhibitor, versus lamivudine, a nucleoside analog reverse transcriptase inhibitor, in a randomized controlled trial of HIV-exposed infants in Africa. Breastfeeding infants born to HIV-infected mothers and included in the study were randomly assigned on day 7 after birth to either lopinavir-ritonavir or lamivudine until a follow-up period of 50 weeks.

The results showed no significant difference in the number of infants infected by HIV in either group, but were both effective at achieving low rates of infection, with 17 of 1,236 infants infected overall, including 8 in the lopinavir-ritonavir group and 9 in the lamivudine group. Severe adverse events did not significantly differ between groups. The most common severe adverse events included anemia, neutropenia, malaria, hyponatremia, and pneumonia. This study was strengthened by the high adherence rate of participants, but limited by the low number of infections resulting in a low power to detect a difference between the study groups.

Click to read the study in The Lancet

Relevant Reading: Maternal and infant antiretroviral regimens to prevent postnatal HIV-1 transmission: 48-week follow-up of the BAN randomised controlled trial

In-Depth [randomized controlled trial]: This study enrolled 1,273 infants and analyzed 1,236 from four sites in Burkina Faso, South Africa, Uganda, and Zambia between 2009 and 2012. Children were eligible at day 7 after birth if they were breastfed, had a negative HIV-1 DNA PCR at day 7, received any prevention of mother-to-child transmission program; and if the mother was older than 18, infected by HIV-1, intended to continue breastfeeding, was not eligible for antiretroviral therapy with a CD4 count of <350 cells/μL, and had received any perinatal antiretroviral prophylactic drugs during pregnancy or delivery. 615 infants were randomly assigned to receive lopinavir-ritonavir and 621 to lamivudine twice per day in pediatric liquid formulas. The primary outcome was HIV-1 infection between 7 days and 50 weeks.

33 (3%) infants died during follow-up and 1,112 (88%) completed follow-up. The median duration of breastfeeding was 41.1 weeks (IQR 34.4-45.6) in the lopinavir-ritonavir group and 41.4 weeks (35.9-46.7) in the lamivudine group. Overall, 17 infants were diagnosed with HIV-1 infections during the follow-up period, including 8 in the lopinavir-ritonavir group (1.4%, 95% CI 0.4-2.5) and 9 in the lamivudine group (1.5%, 0.7-2.5); p=0.83), resulting in a hazard ratio of 0.90 (95% CI 0.35-2.34; p=0.83). Additionally, 8 of the 17 infections (47%) occurred after 6 months of breastfeeding. 497 severe adverse events were reported overall, with 251 (51%) in the lopinavir-ritonavir group and 246 (50%) in the lamivudine group (p=0.86).

Image: PD

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