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Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND)

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Abstract

HIV-associated neurocognitive disorders (HAND) continues to be prevalent (30–50 %) despite plasma HIV-RNA suppression with combination antiretroviral therapy (cART). There is no proven therapy for individuals on suppressive cART with HAND. We have shown that the degree of HIV reservoir burden (HIV DNA) in monocytes appear to be linked to cognitive outcomes. HIV infection of monocytes may therefore be critical in the pathogenesis of HAND. A single arm, open-labeled trial was conducted to examine the effect of maraviroc (MVC) intensification on monocyte inflammation and neuropsychological (NP) performance in 15 HIV subjects on stable 6-month cART with undetectable plasma HIV RNA (<48 copies/ml) and detectable monocyte HIV DNA (>10 copies/106 cells). MVC was added to their existing cART regimen for 24 weeks. Post-intensification change in monocytes was assessed using multiparametric flow cytometry, monocyte HIV DNA content by PCR, soluble CD163 (sCD163) by an ELISA, and NP performance over 24 weeks. In 12 evaluable subjects, MVC intensification resulted in a decreased proportion of circulating intermediate (median; 3.06 % (1.93, 6.45) to 1.05 % (0.77, 2.26)) and nonclassical (5.2 % (3.8, 7.9) to 3.2 % (1.8, 4.8)) CD16-expressing monocytes, a reduction in monocyte HIV DNA content to zero log10 copies/106 cells and in levels of sCD163 of 43 % by 24 weeks. This was associated with significant improvement in NP performance among six subjects who entered the study with evidence of mild to moderate cognitive impairment. The results of this study suggest that antiretroviral therapy with potency against monocytes may have efficacy against HAND.

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Acknowledgments

We thank our study participants and community physicians for their roles in this study, Dr. Mark S. Shaefer (ViiV Healthcare) for the donation of Maraviroc and Mr. Kawakahi Amina for assistance with ELISA studies. No conflicts of interest are declared by all co-authors. This work was presented in part at the 19th and 20th Conference on Retroviruses and Opportunistic Infections (CROI) in March 5–8, 2012 at Seattle, WA, USA and March 3–6, 2013 at Atlanta, GA, USA. This work was supported in part by NIH/NIMHD grant U54MD007584, G12MD007601, and U19MH081835 McGrath, M (PI) [UCSF].

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  1. Hawaii Center for AIDS, University of Hawai’i, 651 Ilalo St, BSB 325C, Honolulu, HI, 96815, USA

    Lishomwa C. Ndhlovu, Tracie Umaki, Glen M. Chew, Dominic C. Chow, Melissa Agsalda, Kalpana J. Kallianpur, Erika Ho, Nancy Hanks, Beau Nakamoto, Bruce T. Shiramizu & Cecilia M. Shikuma

  2. Department of Tropical Medicine, University of Hawai’i, 651 Ilalo St, BSB 325C, Honolulu, HI, 96815, USA

    Lishomwa C. Ndhlovu, Melissa Agsalda & Bruce T. Shiramizu

  3. Biostatistics and Data Management Core, John A. Burns School of Medicine, University of Hawai’i, Honolulu, HI, USA

    Guangxiang Zhang

  4. Department of Psychology, University of Missouri, St. Louis, MO, USA

    Robert Paul

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  1. Lishomwa C. Ndhlovu
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Ndhlovu, L.C., Umaki, T., Chew, G.M. et al. Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND). J. Neurovirol. 20, 571–582 (2014). https://doi.org/10.1007/s13365-014-0279-x

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