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Effects on immune system and viral reservoir of a short-cycle antiretroviral therapy in virologically suppressed HIV-positive patients

Guardo, Alberto C.a; Zarama, Angelaa; González, Taniaa; Bargalló, Manel Enrica; Rojas, Johnb; Martínez, Estebanb; Plana, Montserrata,*; Sánchez-Palomino, Sonsolesa,*

doi: 10.1097/QAD.0000000000002169
BASIC SCIENCE
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Background: Atripla dose reduction decreases subclinical toxicity and maintains viral suppression in HIV+ individuals but the virological efficacy and immunological safety of this strategy needs to be further confirmed.

Methods: Virologically suppressed HIV-infected adults on Atripla® once-daily were randomized 1 : 1 to reduce therapy to 3 days a week (3W, n = 30) or to maintain it unchanged (once-daily, n = 31). HIV-1 reservoir (total and integrated HIV-1 DNA in CD4+ cells) and immunological cell activation (CD38 and HLA-DR), senescence (CD57+ and CD28+), apoptosis (annexinV) as well as T-naive, effector memory (TEM) (CCR7, CD45RA) and stem cell memory (TSCM) (CD954+ and CD27+) populations were measured at baseline, 24 and 48 weeks.

Results: No differences on activation, senescence or apoptosis of both CD4+ and CD8+ T cells were observed on follow-up. Nave CD4+ T-cell proportion showed a significant decrease in the 3W group (mean ± SD): 24.6 ± 13.7 vs. 20.5 ± 12.9 (P = 0.002). No differences in both plasma viral load and HIV reservoir were detected on follow-up. CD4+ TSCM levels at 48 weeks correlated with basal integrated HIV-1 DNA in the 3W group but not in the once-daily group. A post hoc analysis of data prior to the study entry revealed a higher viral load zenith and a trend to lower CD4+ nadir in 3W vs. once-daily group.

Conclusion: No significant immunological or viral changes were induced in the 3W group confirming the virological efficacy and immunogical safety of this strategy. In-depth virological and immunological analyses are useful in providing additional information in antiretroviral switching studies (Clinical Trials.gov: NCT01778413).

aLaboratory of Retrovirology and Viral Immunopathology, AIDS Research Group, Hospital Clínic- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)

bInfectious Diseases Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Spain.

Correspondence to Sonsoles Sánchez-Palomino, Laboratory of Retrovirology and Viral Immunopathology, AIDS Research Group, Hospital Clínic- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Villarroel 170, 08036 Barcelona, Spain. Tel: +34 932275400 x4822; fax: +34 934518038; e-mail: ssanchez@clinic.ub.es.

Received 9 May, 2018

Revised 18 January, 2019

Accepted 24 January, 2019

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Copyright © 2019 Wolters Kluwer Health, Inc.