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

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.

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.

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.

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

Below: Change in neuropsychological testing performance (NPZ-4) over 24 weeks by randomized arm. Participants demonstrate improvement with no differences noted by arm.

Full article at:  http://goo.gl/NSOLWz

By: 

Victor G. Valcour, Collin L. Adams, Joanna M. Hellmuth

Department of Neurology, University of California San Francisco, San Francisco, California, United States of America

Serena S. Spudich

Department of Neurology, Yale University, New Haven, Connecticut, United States of America

Napapon Sailasuta

Huntington Medical Research Institutes, Pasadena, California, United States of America

Nittaya Phanuphak, James L. K. Fletcher, Eugene D. M. B. Kroon, Peeriya Prueksakaew, SEARCH 010/RV 254 Study Group

South East Asia Research Collaboration with Hawaii, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand

Sukalaya Lerdlum, Jintanat Ananworanich

Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Eugene D. M. B. Kroon

Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, United States Component, Bangkok, Thailand

Linda L. Jagodzinski, Bonnie M. Slike, Jerome H. Kim, Jintanat Ananworanich

United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America

Isabel E. Allen

Department of Biostatistics and Epidemiology, University of California San Francisco, San Francisco, California, United States of America

Bonnie M. Slike, Jintanat Ananworanich

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America

 

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