Publication Abstract Display
Type: Published Abstract
Title: Compartmentalized HIV Rebound in the Male Genital Tract after ART Interruption.
Authors: Gianella S, Chaillon A, Ignacio C, Chun T, Kovacs C, Benko E, Hubner S, Kaul R
Year: 2019
Publication: CROI
Volume: Issue: Pages:
Abstract:Background: If strategies currently in development succeed in eradicating HIV reservoirs in peripheral blood and lymphoid tissues, residual sources of virus may remain in anatomic compartments, including the genital tract. To design effective eradication strategies, it is crucial to determine to what extent compartmentalized HIV reservoirs contribute to viral rebound after antiretroviral therapy (ART) interruption. Methods: Paired blood and semen samples were collected from 12 individuals enrolled in a randomized, double-blind, placebo-controlled clinical trial of HIV-MAG DNA vaccine prime, rVSVN4CT1gag booster vaccine in people living with HIV (PLWH) who began ART during acute or early infection (NCT01859325). At the first available time-points following viral rebound, we sequenced HIV-1 env (C2-V3), gag (p24), and pol (reverse transcriptase) regions amplified from cell-free HIV RNA in blood and seminal plasma using the MiSeq Illumina platform. Results: Vaccine had no effect on kinetics and magnitude of HIV RNA rebound in blood plasma (Sneller et al, STM 2017). Compared to blood plasma, HIV RNA rebound in semen occurred significantly later (66 versus 42 days post ART interruption) and reached lower levels (median 164 compared to 16,224 copies/ml). In 5 out of 12 participants with available paired sequence data, viral rebound populations were compartmentalized between blood and semen (Fst, p ≤ 0.05 for all genes). Phylogenetic analysis confirmed the presence of monophyletic HIV RNA populations within the semen in participants, suggesting that rebound originated within genital compartment rather than migrating from blood. Interestingly, despite limited numbers of haplotypes and early ART start, genetic diversity was significantly higher in semen compared to blood in all three coding regions. Conclusions: Our study suggests that HIV reservoirs in the genital compartment contribute to viral rebound in most HIV-infected subjects interrupting ART. Reservoirs in all anatomic compartments need to be actively targeted to achieve a complete functional cure.

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