Intensification with maraviroc in HIV‐infected individuals (with or without liver cirrhosis) with a discordant CD4 response to cART

Abstract

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