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Randomized Controlled Trial
. 2015 Nov 10;10(11):e0142600.
doi: 10.1371/journal.pone.0142600. eCollection 2015.

Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV

Victor G Valcour  1 , Serena S Spudich  2 , Napapon Sailasuta  3 , Nittaya Phanuphak  4 , Sukalaya Lerdlum  5 , James L K Fletcher  4 , Eugene D M B Kroon  4   6 , Linda L Jagodzinski  7 , Isabel E Allen  8 , Collin L Adams  1 , Peeriya Prueksakaew  4 , Bonnie M Slike  7   9 , Joanna M Hellmuth  1 , Jerome H Kim  7 , Jintanat Ananworanich  5   7   9 ; SEARCH 010/RV 254 Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV

Victor G Valcour et al. PLoS One. .

Abstract

Objective: To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+).

Design: 24-week randomized open-label prospective evaluation.

Method: Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls.

Results: At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log10 HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group.

Conclusions: A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART.

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Conflict of interest statement

Competing Interests: Dr. Valcour has recently served as a consultant to ViiV Healthcare, who have supported antiretrovirals for this study but have not had input on the analyses or the manuscript. The authors also note that The Thai Government Pharmaceutical Organization (tenofovir, lamivudine, efavirenz), Gilead (Truvada, Atripla), Merck (Sustiva, Isentress), and ViiV Healthcare (Selzentry) provided antiretroviral therapy. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Change in neuropsychological testing performance (NPZ-4) over 24 weeks by randomized arm.
Participants demonstrate improvement with no differences noted by arm.
Fig 2
Fig 2. NAA and Cho changes with treatment cART (white) vs. cART+ (grey) compared to controls (black).
(a) Frontal grey matter (b) Frontal white matter (c) Posterior cingulate gyrus (d) Basal ganglia.
Fig 3
Fig 3. Tukey boxplots of cytokine changes in cART (white) vs. cART+ (grey) compared to controls (black).
IL-6 not displayed because it was constitutively undetectable (controls) and seldom elevated in HIV, particularly in plasma. Neopterin and IP-10 remain elevated in plasma after 24 weeks on ART. CSF cytokines decrease with treatment and appear similar to controls.
See this image and copyright information in PMC

References

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