These data showed that in vitro exposure to maraviroc decreases some activation expression markers on T lymphocytes and also migration towards chemoattractants. These results support the additional immunological effects of CCR5 blockade and suggest that maraviroc might have potential capacity to inhibit HIV-associated chronic inflammation and activation, both by directly affecting T cell activation and by reducing entrapment of lymphocytes in lymph nodes.

BackgroundGeneration of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy.MethodsWe have evaluated the specific T cell response against different types of NL4-3 virions (including NL4-3 aldrithiol-2 treated, NL4-3/ΔRT and R5 envelopes: NL4-3/ΔRT/ΔEnv[AC10] and NL4-3/ΔRT/ΔEnv[Bal]) and against pools of overlapping peptides (15 mer) encompassing the HIV-1 Gag and Nef regions. Cryopreserved PBMC from a subset of 69 chronic asymptomatic HIV positive individuals have been employed using different techniques including IFN-γ ELISPOT assay, surface activation markers and intracellular cytokine staining (ICS) by flow cytometry.ResultsThe differential response obtained against NL4-3 aldrithiol-2 treated and NL4-3/ΔRT virions (25% vs 55%, respectively) allow us to divide the population in three groups: “full-responders” (positive response against both viral particles), “partial-responders” (positive response only against NL4-3/ΔRT virions) and “non-responders” (negative responses). There was no difference between X4 and R5 envelopes. The magnitude of the total responses was higher against NL4-3/ΔRT and was positively correlated with gender and inverse correlated with viral load. On the contrary CD4+ T cell count was not associated with this response. In any case responses to the viruses tended to be lower in magnitude than those detected by the overlapping peptides tested. Finally we have found an increased frequency of HLA-B27 allele (23% vs 9%) and a significant reduction in some activation markers (CD69 and CD38) on T cells surface in responders vs non-responders individuals.ConclusionsIn summary these virions could be considered as alternative and useful reagents for screening HIV-1-specific T cell responses in HIV exposed uninfected people, HIV infected patients and to assess immunogenicity of new prototypes both in vitro and in vaccine trials, by a feasible, simply, effective and low cost assay.

Background: Patients with a discordant response to cART, defined as persistent CD4 + T-cell counts <200 cells/mm3 and lack CD4 increase despite virologic suppression on HAART, have an increased risk of morbidity and mortality. Several studies have suggested a potential benefit of intensification with maraviroc (MVC) on CD4+T-cell recovery. Methods: A 24-week prospective, open-label, randomized, controlled study. Subjects on cART, plasma HIV RNA <37 copies/mL for at least 12 months, and CD4 < 200 cells/L, with CD4-gain in the previous 12 months <50 cells/µL, were randomized to add MVC (A) or continuing same cART (B). Randomisation was stratified by the presence of liver cirrhosis (CH) (n = 10) and non-CH (n = 28). We measured by flow cytometry changes in the following parameters of CD4 + and CD8 + T-cell subsets: activation (CD38, HLA-DR), senescence (CD28, CD57, CD45RA and RO), coreceptors (CCR5 and CXCR4) and apoptosis (Annexin-V). Results: Thirty-eight subjects were included at the final analysis. Median values were: age 51 years (IQR, 44–57), time with VL < 37 copies/mL before entry 43 months (IQR 24–62 months), baseline CD4 + T-cell count 144 cells/µL (IQR 106–181). Four subjects were lost of follow-up (3 in A, 1 in B). One subject from group B experienced confirmed virologic failure at week 24. Adverse events were similar in both arms. Median increase in CD4 + T-cell count from baseline to weeks 2,4 and 24 in both groups were +15.5 vs -1 (p = 0.025); +16.5 vs -2.5 (p = 0.158); +46.5 vs + 6.50 (p = 0.190). Similar trend towards a higher CD4 increase were seen in both CH and non-CH individuals. At W24, 8 subjects from arm A vs 1 subject from arm B achieved a CD4 + T-cell count above 200 cells/µL (p < 0.05). Markers of immune activation (CD38 and HLA-DR) decreased during MVC intensification, especially in CD8+ T cells (p < 0.01) whereas apoptosis did not. Additionally CCR5 expression tended to increase (p = 0.051) in CD8 T cells from arm A subjects. No significant differences were found in the immunological assay between cirrhotic and non cirrhotic individuals. Conclusions: MVC intensification was safe and was associated with a significant a trend towards increasing CD4 + T-cell counts both in cirrhotic as well as non-cirrhotic patients with discordant response. The addition of MVC was associated with a decrease in markers of immune activation in both groups