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Randomized Controlled Trial
. 2014 Jun 1;66(2):140-7.
doi: 10.1097/QAI.0000000000000111.

A randomized open-label study of 3- versus 5-drug combination antiretroviral therapy in newly HIV-1-infected individuals

Martin Markowitz  1 , Teresa H Evering, Donald Garmon, Marina Caskey, Melissa La Mar, Kristina Rodriguez, Vincent Sahi, Sarah Palmer, Nicole Prada, Hiroshi Mohri
Affiliations
Randomized Controlled Trial

A randomized open-label study of 3- versus 5-drug combination antiretroviral therapy in newly HIV-1-infected individuals

Martin Markowitz et al. J Acquir Immune Defic Syndr. .

Abstract

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.

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Conflict of interest statement

Conflict of interest: 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. Additional authors have no conflict of interest to report.

Figures

Figure 1
Figure 1
Patient disposition during 96-weeks of treatment and reasons for premature discontinuation.
Figure 2
Figure 2
The percent of subjects with plasma HIV-1 RNA levels below the level of detection during 96 weeks of treatment with 3-drug therapy (circles) and 5-drug therapy (squares). Number of subjects included in the analysis is shown below the X-axis.
Figure 3
Figure 3
Panel a. Levels of proviral DNA per 106 CD4+ T cells during 96 weeks of treatment with 3-drug therapy (circles) and 5-drug therapy (squares). Panel b. Levels of cell-associated HIV-1 RNA per μg total RNA during 96 weeks of treatment with 3-drug therapy (circles) and 5-drug therapy (squares). Panel c. Levels of infectious HIV-1 in resting CD4+ T cells expressed as infectious units per million cells (IUPM) in subjects after 96 weeks of treatment with 3-drug therapy (circles) and 5-drug therapy (squares).
Figure 4
Figure 4
Panel a. Levels of CD4+ T cells during 96 weeks of treatment with 3-drug therapy (circles) and 5-drug therapy (squares). Panel b. Levels of naïve CD4+ T cells during 96 weeks of treatment with 3-drug therapy (circles) and 5-drug therapy (squares). Panel c. Levels of central memory CD4+ T cells during 96 weeks of treatment with 3-drug therapy (circles) and 5-drug therapy (squares).
See this image and copyright information in PMC

References

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