Virological effectiveness and CD4+ T-cell increase over early and late courses in HIV infected patients on antiretroviral therapy: focus on HCV and anchor class received

Abstract

BackgroundThe aim of this study was to explore the effects of HCV co-infection on virological effectiveness and on CD4+ T-cell recovery in patients with an early and sustained virological response after HAART.MethodsWe performed a longitudinal analysis of 3,262 patients from the MASTER cohort, who started HAART from 2000 to 2008. Patients were stratified into 6 groups by HCV status and type of anchor class. The early virological outcome was the achievement of HIV RNA <500 copies/ml 4–8 months after HAART initiation. Time to virological response was also evaluated by Kaplan-Meier analysis. The main outcome measure of early immunological response was the achievement of CD4+ T-cell increase by ≥100/mm3 from baseline to month 4–8 in virological responder patients. Late immunological outcome was absolute variation of CD4+ T-cell count with respect to baseline up to month 24. Multivariable analysis (ANCOVA) investigated predictors for this outcome.ResultsThe early virological response was higher in HCV Ab-negative than HCV Ab-positive patients prescribed PI/r (92.2% versus 88%; p = 0.01) or NNRTI (88.5% versus 84.7%; p = 0.06). HCV Ab-positive serostatus was a significant predictor of a delayed virological suppression independently from other variables, including types of anchor class. Reactivity for HCV antibodies was associated with a lower probability of obtaining ≥100/mm3 CD4+ increase within 8 months from HAART initiation in patients treated with PI/r (62.2% among HCV Ab-positive patients versus 70.9% among HCV Ab-negative patients; p = 0.003) and NNRTI (63.7% versus 74.7%; p < 0.001). Regarding late CD4+ increase, positive HCV Ab appeared to impair immune reconstitution in terms of absolute CD4+ T-cell count increase both in patients treated with PI/r (p = 0.013) and in those treated with NNRTI (p = 0.002). This was confirmed at a multivariable analysis up to 12 months of follow-up.ConclusionsIn this large cohort, HCV Ab reactivity was associated with an inferior virological outcome and an independent association between HCV Ab-positivity and smaller CD4+ increase was evident up to 12 months of follow-up. Although the difference in CD4+ T-cell count was modest, a stricter follow-up and optimization of HAART strategy appear to be important in HIV patients co-infected by HCV. Moreover, our data support anti-HCV treatment leading to HCV eradication as a means to facilitate the achievement of the viro-immunological goals of HAART.

IL7RA polymorphisms predict the CD4+ recovery in HIV patients on cART

“…After a given cART achieves an undetectable HIV viral load, we think that the influence of the drug used might be secondary except for the side effects that may result in poorer adherence. (iii) HCV infection has also an influence on CD4+ T‐cell recovery . In our study, around 30% of the patients had HCV infection at baseline and no patient was treated in the analysed follow‐up period.…”

Hepatitis C virus/HIV coinfection and responses to initial antiretroviral treatment

“…HCV/HIV is also causing health burden worldwide [3, 4]. Despite extensive research and subsequently better understanding of the negative effects of HIV infection on HCV replication, persistence and liver fibrogenesis [5-8], whether HCV is associated with HIV progression continues to be debated.…”

“…However, inconsistent results have been reported for CD4 and HIV virologic responses to ART as well as HIV progression and mortality. While some studies have shown that HCV co-infection is associated with either smaller CD4 increases after initiation of ART [11-16] or a delayed CD4 response [17], other studies report early detected differences in CD4 response wane over time [4, 18]. Many studies have not found such an association [3, 19-25].…”

Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment

“…[21][22][23] For other factors, particularly for low CD4, which was a significant predictor of quantifiable viral load in univariate analyses, the limited sample size may have reduced the power to maintain statistical significance in the multivariable analysis.…”