A Randomized Open-Label Study of 3- Versus 5-Drug Combination Antiretroviral Therapy in Newly HIV-1Infected Individuals

Markowitz, Martin MD*; Evering, Teresa H. MD, MS*; Garmon, Donald NP*; Caskey, Marina MD; La Mar, Melissa BA*; Rodriguez, Kristina MPH*; Sahi, Vincent MS*; Palmer, Sarah PhD; Prada, Nicole PhD*; Mohri, Hiroshi MD, PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 June 2014 - Volume 66 - Issue 2 - p 140–147
doi: 10.1097/QAI.0000000000000111
Clinical Science

Background: To understand whether combination antiretroviral therapy (cART) has been optimized, we asked whether 3-drug protease inhibitor (PI)-based cART intensified with raltegravir and maraviroc and initiated during early infection would improve outcomes when compared with similarly applied 3-drug PI-based cART.

Methods: Forty newly HIV-1–infected patients were randomized 1:2 to receive 3-drug (N = 14) or 5-drug (N = 26) therapy. The primary end point was the percent of subjects with undetectable plasma viremia using standard reverse transcriptase–polymerase chain reaction and the single copy assay after 48 weeks. Secondary end points included levels of cell-associated HIV-1 DNA and RNA and levels of infectious virus in resting CD4+ T cells at week 96 and quantitative and qualitative immunologic responses.

Results: At 48 weeks, 34 subjects remained on study and are included in the as-treated analysis. Three of 11 (27.3%) in the 3-drug arm and 9 of 21 (42.9%) in the 5-drug arm had plasma HIV-1 RNA levels below detection by both standard reverse transcriptase–polymerase chain reaction and single copy assay (P = 0.46, Fisher exact test). No significant differences in absolute levels of proviral DNA or changes in cell-associated RNA were seen during 96 weeks of therapy. Mean levels of infectious HIV-1 in resting CD4+ T cells at week 96 in 7 subjects treated with 3-drugs and 13 with 5-drugs were 0.67 and 0.71 infectious units per million, respectively (P = 0.81). No differences were seen in quantitative or qualitative immunologic determinations including markers of immune activation.

Conclusions: Intensified 5-drug cART initiated during early infection fails to significantly further impact virologic or immunologic responses beyond those achieved with standard 3-drug PI-based cART.

*Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY;

The Rockefeller University, New York, NY; and

Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Solna, Sweden (Dr Palmer is now with the Westmead Millennium Institute for Medical Research and University of Sydney, Westmead, New South Wales, Australia).

Correspondence to: Martin Markowitz, MD, Aaron Diamond AIDS Research Center, 455 First Avenue, 7th Floor, New York, NY, 10016 (e-mail: mmarkowitz@adarc.org).

Supported by a Grant from Merck Laboratories and Pfizer; in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (RO1 AI047033 and U19 AI067854), National Center for Advancing Translational Sciences (NCATS), and National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program (UL1 TR000043).

Presented in part at the 18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston, MA, and the HIV Persistence During Therapy Workshop, December 6–9, 2011, St. Maarten, the Netherlands.

M.M. is a paid consultant to Merck, Gilead Sciences, and Janssen, serves on the speaker's bureau for Gilead Sciences, Bristol-Myers Squibb, and Janssen, and has received Grant support from Merck, Pfizer, Gilead Sciences, GlaxoSmithKline, and Tobira within the past 24 months. The remaining authors have no funding or conflicts of interest to disclose.

Received September 20, 2013

Accepted January 02, 2014

© 2014 by Lippincott Williams & Wilkins