Dynamics of the HIV-1 latent reservoir after discontinuation of the intensification of antiretroviral treatment: results of two clinical trials

Gutiérrez, Carolinaa; Hernández-Novoa, Beatriza; Vallejo, Alejandroa; Serrano-Villar, Sergioa; Abad-Fernández, Maríaa; Madrid, Nadiaa; Díaz, Laurab; Moreno, Anaa; Dronda, Fernandoa; Zamora, Javierc; Muñoz-Fernández, María Ángelesb; Moreno, Santiagoa

doi: 10.1097/QAD.0b013e328361d0e1
Clinical Science

Objective: Antiretroviral therapy (ART) intensification has been shown to reduce the reservoir of latently infected CD4+ T cells. However, it is currently unknown whether this effect is maintained after discontinuation of the intensifying drug.

Design: The effect of ART intensification during 48 weeks with maraviroc or raltegravir in chronically HIV-1-infected patients was assessed in two previous clinical trials. In this study, we analysed this effect at week 24 after discontinuation of the intensifying drugs, at baseline and 48 weeks of intensification.

Methods: We measured the latently infected memory CD4+ T cells carrying replication-competent virus, 2-long terminal repeat (2-LTR) circles and CD4+/CD8+ T cells activation.

Results: Fifteen patients were evaluated. After 48 weeks of intensification, HIV-1 reservoir size significantly decreased from 1.1 to 0.0 infectious units per million (IUPM) (P = 0.004). After 24 weeks of drug discontinuation, the median size of the reservoir was still significantly lower than at baseline (P = 0.008). 2-LTRs were undetectable in all individuals at baseline and after 48 weeks of intensification, continuing undetectable in all patients except two at week 24 after discontinuation (P = 0.1). CD4+ and CD8+ T-cell activation significantly decreased at 48 weeks after intensification, without further increase after discontinuation.

Conclusion: The effects of ART intensification with maraviroc or raltegravir persist at least 24 weeks after discontinuation of the drug. In a global strategy, ART intensification should be considered as part of a combination approach to achieve a functional cure or HIV eradication.

aInfectious Diseases Department, Hospital Universitario Ramón y Cajal, and IRYCIS

bImmunobiology Laboratory, Hospital General Universitario Gregorio Marañón

cBiostatistics Department, Hospital Universitario Ramón y Cajal, and IRYCIS, Madrid, Spain.

Correspondence to Dr Santiago Moreno, Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Carretera de Colmenar Km 9,1, 28034 Madrid, Spain. Tel: +34 91 336 8710; fax: +34 91 336 8792; e-mail: smoreno.hrc@salud.madrid.org

Received 13 February, 2013

Revised 22 March, 2013

Accepted 29 March, 2013

This work has been previously presented at the 19th Conference on Retroviruses and Opportunistic Infections (CROI); 5–8 March 2012; Seattle (Washington, USA).

© 2013 Lippincott Williams & Wilkins, Inc.