HIV clinical trials PROMISE-PEP and 2LADY: results presented at CROI 2014

Published on 7 March 2014

Today, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) held a press conference in Paris to highlight results from several studies presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2014) in Boston (Ma), United States. Among the studies presented were two EDCTP cofunded clinical trials, PROMISE-PEP and 2LADY.

The PROMISE-PEP study was coordinated by Prof. Philippe Van de Perre (University of Montpellier 1, France). It aimed to evaluate antiretroviral treatment in infants to prevent mother to child transmission of HIV. The study concluded follow-up of the infants in May 2013 and the final results were presented at CROI this year. These confirmed the preliminary results presented at CROI 2013 and offered a more precise analysis regarding the efficacy of each regimen.

PROMISE-PEP clinical trial compared two prophylactic treatment regimens to prevent transmission of HIV from mother to child during 12 months of breastfeeding. Infant Lopinavir/Ritonavir (LPV/r) treatment was compared to Lamivudine (3TC) treatment from day 7 until 4 weeks after cessation of breastfeeding (maximum duration of prophylaxis: 50 weeks for a recommended maximum duration of breastfeeding of 49 weeks). These treatments have not been ever evaluated before for such an extended period of 50 weeks.

This trial presents the first data on the efficacy of a treatment strategy to prevent mother-to-child transmission of HIV-1 during 12 months of breastfeeding. The transmission rate of the disease from mother to child was reported as 1.4% at 12 months, the lowest rate ever reported during breastfeeding according to the PROMISE-PEP team. Moreover, the survival rate was 96.5 % among infants who remained uninfected for a period of 50 weeks, which is the highest rate ever reported, corroborating the health benefits of ART prophylactic treatment during breastfeeding. There was no significant difference in efficacy and tolerance of the two regimens between the two groups studied. The study supports the use of LPV/r as a good alternative to the 3TC treatment.

The 2LADY project is coordinated by Prof. Eric Delaporte (University of Montpellier, France) and Prof. Sinata Koulla Shiro (University of Yaounde, Cameroon). The study aims to evaluate the two WHO recommended second-line treatments for HIV infection. The phase III clinical trial was conducted in Burkina Faso, Senegal and Cameroon between November 2009 and October 2013. The project will finish in September 2014. Preliminary results were presented at CROI 2014.

Highly active antiretroviral therapy (ART) has dramatically altered the prognosis of individuals infected with HIV. In low-income countries with a high burden of HIV and AIDS, there has been a concerted effort to increase access to ART. With this increasing exposure to ART, the risk of resistance and subsequent treatment failure has become a major consideration. Switching patients to alternative second-line regimens will be increasingly necessary. The study also illustrates the importance of early diagnosis of therapeutic failure in diminishing the emergence of resistant viral strains.

This clinical trial compares the efficacy and tolerance of three different second line treatment strategies: two recommended by WHO which combine two non-nucleoside reverse transcriptase inhibitors associated with a ritonavir boosted protease inhibitor (Arm A: emtricitabine-tenofovir-lopinavir/ritonavir, Arm B: abacavir-didanosine-lopinavir/ritonavir; and Arm C: emtricitabine-tenofovir-darunavir/ritonavir). The combination strategy in Arm C had not been evaluated in sub-Saharan Africa. Moreover, darunavir is taken once daily which may facilitate treatment adherence.

The drug combinations in the Arms B and C were found to be non-inferior to the combination of antiretroviral drugs in Arm A. No differences between the three study arms as regards median CD4 cell count, severe adverse events and mortality were observed. The use of second-line antiretrovirals with a boosted protease inhibitor showed good efficacy results. The regimens recommended by WHO remain therefore valid options for countries with limited resources.

More information
• ANRS press release (in French)
• PROMISE-PEP EDCTP project profile
• 2LADY EDCTP project profile



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