Responses to switching to maraviroc-based antiretroviral therapy in treated patients with suppressed plasma HIV-1-RNA load.
ABSTRACT Maraviroc (MVC) has shown good efficacy and tolerability in treatment-naive and treatment-experienced HIV-1-infected patients with CCR5-tropic virus. Data on patients switching to MVC while on suppressive antiretroviral therapy (ART) are limited. The aim of this study was to evaluate patients on suppressive ART switching to an MVC-containing regimen (MVC-CR), and test the hypothesis that the switch may have an impact on T cell activation.
The study population comprised 20 treated adults who started MVC with a plasma HIV-1-RNA load (viral load, VL) of <50 copies/ml. Viral tropism was assessed by V3 loop sequencing using proviral DNA from peripheral blood mononuclear cells (PBMCs). Changes in clinical and laboratory parameters were evaluated at a median of 2 and 6 months of follow-up. T cell activation was determined by measuring soluble CD30 in plasma.
Reasons for switching to a MVC-CR were drug toxicity and tolerability, low CD4 cell count and ART simplification. Over median 7.5 months of follow-up, 3/20 patients discontinued MVC due to severe headache, fatigue and VL rebound. A significant reduction in soluble CD30 levels in MVC-treated patients was observed during follow-up at both 2 (p = 0.027) and 6 months (p = 0.001).
Switching suppressive ART to a MVC-CR based upon genotypic tropism prediction from proviral DNA improves tolerability. The observed impact on T cell activation warrants further investigation.
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ABSTRACT: HIV co-receptor tropism testing is recommended before therapy when the C-C chemokine receptor type 5 antagonist maraviroc is initiated. This review addresses the use of population genotypic tropism testing in relation to clinical practice. Genotypic tropism tests predict viral co-receptor tropism based on the sequence of the V3 loop of the viral envelope. HIV occurs in a swarm of variants in the patient's body, called quasispecies. As next-generation sequencing techniques are not generally accessible to date, triplicate testing is often performed to improve sensitivity of population-based approaches, but no prospective studies assessing the performance of single and triplicate procedures related to clinical outcome have been performed yet. For interpretation of the genotype several web-based algorithms have been developed. Varying the cut-off of the commonly used geno2pheno[co-receptor] algorithm changes the sensitivity and specificity of the tropism prediction. In retrospective analyses of clinical studies and cohorts genotypic population tropism testing demonstrated equal correlation with clinical outcome on maraviroc compared with phenotypic assays.In patients with suppressed viraemia, proviral DNA testing is a well tolerated alternative to HIV-RNA testing. Population genotypic methods have greater accessibility, lower cost, and faster turnaround time than other methods. Despite limited sensitivity for minority variants HIV genotypic population tropism testing showed good correlation with clinical outcome.Current opinion in HIV and AIDS 07/2012; 7(5):470-7. · 4.75 Impact Factor
Anna Maria Geretti