Viral rebound in semen after antiretroviral treatment interruption in an HIV therapeutic vaccine double-blind trial
Résumé
OBJECTIVES: This study aimed to determine the timing and level of HIV rebound in blood and seminal plasma and to characterize the HIV rebounding populations after antiretroviral treatment interruption (ATI) in HIV-1-infected participants enrolled in a therapeutic vaccine trial. DESIGN: A twelve-week (W) ATI period was proposed at W36 to patients enrolled in the VRI02/ANRS149-LIGHT trial. Paired blood and semen samples were collected before (W32 or W36) and during ATI (W38, W40, W42, W44 and W48). METHODS: HIV-RNA and HIV-DNA were quantified sequentially from blood and semen samples. Ultradeep sequencing (UDS, Roche/454) of partial env HIV-DNA/RNA (C2V3) was performed in both compatments. RESULTS: HIV-RNA rebounded in blood plasma and seminal plasma of all ten participants after ATI (median peak of 5.12 log10 cp/ml [range: 4.61-6.35] and 4.26 log10 cp/ml [3.20-4.67], respectively). HIV-RNA rebound was detected in blood plasma as soon as W38 in 8/10 patients, and in seminal plasma between W38 and W40 in 8/10 patients. Phylogenetic approaches showed intermingled HIV-RNA populations from plasma and semen during ATI, suggesting a lack of viral compartmentalization between blood and semen. CONCLUSION: Our data demonstrate rapid and high HIV rebound in semen after ATI, raising concerns about high risk of HIV sexual transmission during HIV cure trials.