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Viral rebound in semen after antiretroviral treatment interruption in an HIV therapeutic vaccine double-blind trial

Palich, Romaina,*; Ghosn, Jadeb,*; Chaillon, Antoinec,d,*; Boilet, Valéried,e; Nere, Marie-Laurea; Chaix, Marie-Laurea,d; Delobel, Pierref; Molina, Jean-Michelg; Lucht, Frédérich; Bouchaud, Olivieri; Rieux, Véroniqued,j; Thiebaut, Rodolphed,e; Levy, Yvesd,k; Delaugerre, Constancea,d; Lelievre, Jean-Danield,k for the VRI02/ANRS149 LIGHT Vaccine Trial Group

doi: 10.1097/QAD.0000000000002058
CLINICAL SCIENCE: CONCISE COMMUNICATION

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 12-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 compartments.

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.

aDépartement de Virologie, Hôpital Saint-Louis, APHP, Inserm U941, Université Paris Diderot

bUnité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpital Hôtel-Dieu, APHP, Université Paris Descartes, Paris, France

cDepartment of Medicine, University of California San Diego (UCSD), San Diego, California, USA

dVaccine Research Institute (VRI), Paris

eINSERM U1219, INRIA SISTM, Université de Bordeaux, Bordeaux

fDépartement de Maladies Infectieuses, Hôpital Pierre-Paul Riquet, Toulouse

gDépartement de Maladies Infectieuses, Hôpital Saint-Louis, APHP, Paris

hDépartement de Maladies Infectieuses, CHU de Saint-Etienne, Saint-Etienne

iDépartement de Maladies Infectieuses, Hôpital Avicenne, APHP

jAgence Nationale Française de Recherche sur le Sida et les Hépatite Virales (ANRS)

kHôpital Henri Mondor, APHP, INSERM U955, Paris, France.

Correspondence to Romain Palich, and Constance Delaugerre, Laboratoire de Virologie, Hôpital Saint-Louis, APHP, 1 avenue Claude Vellefaux, 75010 Paris, France. Tel: +33 1 42 49 94 93; fax: +33 1 42 49 92 00; e-mails: romain.palich@aphp.fr and constance.delaugerre@aphp.fr

Received 30 June, 2018

Accepted 21 September, 2018

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