Levels of intracellular HIV-DNA in patients with suppressive antiretroviral therapy

Cuzin, Lisea; Pugliese, Pascalb; Sauné, Karinec,d; Allavena, Clotildee; Ghosn, Jadef,g; Cottalorda, Jacquelineh; Rodallec, Audreyi; Chaix, Marie Laurej; Fafi-Kremer, Samirak; Soulié, Cathial,m,n; Ouka, Marlèneo; Charpentier, Charlottep,q,r; Bocket, Laurences; Mirand, Audreyt; Guiguet, Margueriteu; for the Dat’AIDS study group

doi: 10.1097/QAD.0000000000000723
Clinical Science: Concise Communications

Objective: The objective of this study is to study factors associated with HIV-DNA levels in chronically infected patients on long-term suppressive antiretroviral therapy (ART).

Design: A cross-sectional, multicentre study of patients receiving ART for more than 3 years, HIV-RNA less than 50 copies/ml for more than 2 years and CD4+ cell count more than 350 cells/μl.

Method: Factors associated with low (<150) or high (>1000), compared with intermediate (150–1000 copies/106 PBMCs) levels of HIV-DNA were investigated using multinomial logistic regression.

Results: Five hundred and twenty-two patients who initiated ART during the chronic phase were included (71% male; median peak HIV-RNA: 4.88 log10 copies/ml, CD4+ cell count nadir: 222 cells/μl). Median ART duration was 13 years [interquartile range (IQR) 7–17], viral suppression was 5.7 years (IQR 3.9–8.5) and 66% of the patients never experienced ART failure. Median HIV-DNA was 323 copies/106 PBMCs (IQR, 129–717) with low, intermediate and high levels observed in 28.3, 55.4 and 16.3%, respectively. In multivariable analysis, women were more likely to achieve a low level of HIV-DNA. Each additional year with suppressed HIV-RNA increased the likelihood of low level and decreased the likelihood of high level of HIV-DNA. Peak HIV-RNA higher than 5log10 was always associated with a decreased risk of low and an increased risk of high HIV-DNA. For patients with peak HIV-RNA lower than 5log10, past ART failure was associated with high level of HIV-DNA.

Conclusion: Chronically HIV-infected patients with long-term suppressive ART can achieve low total HIV-DNA but one over six still presented HIV-DNA above 1000 copies/106 PBMCs despite long-term viral suppression.

aRegional Center for HIV Care and Coordination, INSERM UMR1027, Toulouse 3 University, Toulouse

bInfectious Diseases Dpt, CHU Archet, Nice

cINSERM, U1043, Centre de Physiopathologie de Toulouse Purpan

dCHU Toulouse, Hôpital Purpan, Virology Department, National Reference Center for Hepatitis E, Institut fédératif de biologie de Purpan, Toulouse

eInfectious Diseases Department, CHU Hotel Dieu, Nantes

fAPHP, Department of Therapeutics in Infectious Diseases, Hotel Dieu Hospital

gParis Descartes University, EA 7327, Sorbonne Paris Cité, Paris

hVirology Department, CHU Nice, Nice

iVirology Department, CHU Nantes, Nantes

jVirology Department, AP-HP, Hôpital Saint Louis, INSERM U941, Paris Diderot University, Paris

kVirology Department, CHU Strasbourg, Strasbourg

lSorbonne University, UPMC Univ. Paris 06-UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health

mINSERM-UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health

nAP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, Paris

oVirology laboratory, University Hospital of Martinique, Fort-de-France

pINSERM, IAME, UMR 1137

qUniv Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité

rAP-HP, Hôpital Bichat-Claude Bernard, Virology Department, Paris

sVirology Department, CHU Lille, Lille

tCHU Clermont Ferrand, Laboratoire de Virologie, Hôpital Gabriel Montpied, Clermont-Ferrand

uSorbonne Universities, UPMC Univ. Paris 06, INSERM, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris, France.

*Dat’AIDS Study Group members are listed in the Acknowledgements.

Correspondence to Lise Cuzin, COREVIH - Batiment Turiaf - Hopital Purpan - TSA40031, 31059 Toulouse cedex, France. E-mail: cuzin.l@chu-toulouse.fr

Received 4 February, 2015

Revised 8 April, 2015

Accepted 13 April, 2015

Copyright © 2015 Wolters Kluwer Health, Inc.