The PROMISE PEP study is a clinical trial that will measure the efficacy and the safety of prolonged peri-exposure prophylaxis (PEP) with lamivudine (3TC) to prevent HIV-1-transmission through breast milk in children born to HIV-1-infected mothers not eligible for HAART and having benefited from perinatal antiretroviral (ART) regimens. The study will recruit 1500 mother-infant pairs in 4 African countries.

Study design:

PROMISE PEP is a multinational, randomised double-blind placebo-controlled clinical trial.

Intervention:

Infants will be randomised to receive 3TC or placebo once daily from day seven (± 2 days) after birth until 4 weeks after cessation of breastfeeding (BF). We will recommend exclusive BF (EBF) up till including the 26th week of life followed by a relatively rapid (maximum of 8 weeks) cessation period.

The maximum duration of PEP will thereby be 38 weeks.

Primary objective:

• To measure the efficacy of PEP with 3TC once daily from day 7 until 4 weeks after cessation of BF (maximum duration of prophylaxis: 38 weeks for a maximum duration of breastfeeding of 34 weeks) on the risk of postnatal HIV-1 acquisition between 7 days and 38 weeks of age

Secondary objectives:

• To measure the efficacy of PEP on HIV-1 free survival at 38 weeks and at one year of age ;
• To assess the safety of long-term prophylaxis with 3TC (including adverse events, resistance to lamivudine and growth) until 38 weeks and at one year of age ;
• To build clinical trials capacity at the four study sites ;

Main endpoint:

Acquisition of HIV-1 (as determined by HIV-1 DNA PCR) between day 7 and 38 weeks of age.

Study population:

Seronegative infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants and who have benefited from a standard prevention of mother to child transmission (PMTCT) program during pregnancy and delivery. The study will recruit 1500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia.

Study duration:

Infants will be followed up for one year and the total study duration is five years.

Expected outcome:

This study will measure the efficacy of a new drug regimen to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies for 34 weeks. If found to be sufficiently efficacious, the regimen would contribute to counteract the existing contradiction between optimal infant feeding and MTCT through breast milk.