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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

Davide Motta1, Nigritella Brianese1, Emanuele Focà1*, Paola Nasta8, Franco Maggiolo2, Massimiliano Fabbiani3, Giuliana Cologni2, Simona Di Giambenedetto3, Massimo Di Pietro4, Nicoletta Ladisa5, Laura Sighinolfi6, Silvia Costarelli7, Filippo Castelnuovo8 and Carlo Torti19

Author Affiliations

1 Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy

2 Department of Infectious Diseases, Ospedali Riuniti, Bergamo, Italy

3 Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy

4 Infectious Diseases Clinic, Santa Maria Annunziata Hospital, Florence, Italy

5 Clinic of Infectious Diseases, Policlinico di Bari, Bari, Italy

6 Department of Infectious Diseases, S. Anna Hospital, Ferrara, Italy

7 Department of Infectious Diseases, Istituti Ospitalieri, Cremona, Italy

8 Spedali Civili di Brescia, Brescia, Italy

9 Unit of Infectious Diseases, University “Magna Graecia”, Catanzaro, Italy

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AIDS Research and Therapy 2012, 9:18  doi:10.1186/1742-6405-9-18

Published: 15 June 2012

Abstract

Background

The 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.

Methods

We 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.

Results

The 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.

Conclusions

In 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.

Keywords:
HIV; HCV; HAART