Background: Antiretroviral treatment interruption (ATI) leads to HIV replication rebound in both blood and semen, however dynamic of HIV-RNA rebound in semen is poorly known. We compared HIV-RNA timing of and level of rebound in blood and seminal plasmas (BP-SP) and characterized the HIV rebounding populations in both compartments after ATI in HIV-1 infected patients enrolled in the therapeutic vaccine trial VRI02/ANRS149-LIGHT.
Methods: Ten male from the VRI02/ANRS149-LIGHT trial with CD4 cells ≥600/mm3 and HIV-RNA < 50cp/ml under treatment for at least 18 months were studied. ATI occurred from week (W)36 to W48. Paired blood and semen samples were collected at W32 (before ATI), W36, W38, W40, W42, W44 and W48 following ATI, for HIV-RNA and DNA quantification. Ultradeep sequencing (UDS, 454/Roche) of partial env (C2/V3) HIV-DNA and -RNA was performed in 5 out of 10 participants in PBMC before ATI and in plasma/semen during ATI. Sequenced reads were quality filtered and assembled using an in-house data processing pipeline.
Results: Patients had sustained suppressed blood viral load for a median of 44 months (range: 28-152) before ATI. HIV-RNA rebounded in blood and semen in all patients after ATI (median 5.12 log10 cp/ml (range: 4.61-6.35) and 4.26 log10 cp/ml (range: 3.20-4.67), respectively). BP HIV-RNA rebounded as soon as W38 in 8/10 patients, and SP HIV-RNA between W38 and W40 in 8/10 patients. HIV-DNA median level was 2.97 log10 cp/106 PBMC (range: 1.61-3.26) at W32 and 3.30 log10 cp/106 PBMC (range: 2.50-3.67) at W44. Non-sperm cells HIV-DNA was detected in at least one sample in 6/10 patients. Phylogenetic analysis of UDS revealed that 1) rebounding HIV-RNA population in BP and in SP originated from PBMC HIV-DNA at the time of ATI and 2) intermingled HIV-RNA populations in BP and in SP with no evidence of compartmentalization.
Conclusions: The rapid and intense HIV RNA rebound observed very early both in blood and semen after ATI emphasizes the need for targeted prevention strategies to reduce the risk of sexual transmission during ATI. PBMC HIV-DNA is the major contributor for HIV-RNA rebound in both compartments, even after several years of sustained suppressed viral replication.