We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per μL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir–ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263.
Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir–ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir–ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1·4% (95% CI 0·4–2·5) and 1·5% (0·7–2·5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir–ritonavir versus lamivudine of 0·90, 95% CI 0·35–2·34; p=0·83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3–4 event in the lopinavir–ritonavir group compared with 246 (50%) in the lamivudine group.
Infant HIV-1 prophylaxis with lopinavir–ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding.
INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway.