A randomized open-label study of 3- versus 5-drug combination antiretroviral therapy in newly HIV-1-infected individuals.
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).
Martin
M
Markowitz
Teresa H
TH
Evering
Donald
D
Garmon
Marina
M
Caskey
Melissa
M
La Mar
Kristina
K
Rodriguez
Vincent
V
Sahi
Sarah
S
Palmer
Nicole
N
Prada
Hiroshi
H
Mohri
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D004338:Drug Combinations; D023381:Endpoint Determination; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D011760:Pyrrolidinones / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D014230:Triazoles / Q000627:therapeutic use; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy
D019380:Anti-HIV Agents; D003510:Cyclohexanes; D004279:DNA, Viral; D004338:Drug Combinations; D011760:Pyrrolidinones; D012367:RNA, Viral; D014230:Triazoles; D000068898:Raltegravir Potassium; D000077592:Maraviroc