Research Article: 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

Date Published: June 15, 2012

Publisher: BioMed Central

Author(s): Davide Motta, Nigritella Brianese, Emanuele Focà, Paola Nasta, Franco Maggiolo, Massimiliano Fabbiani, Giuliana Cologni, Simona Di Giambenedetto, Massimo Di Pietro, Nicoletta Ladisa, Laura Sighinolfi, Silvia Costarelli, Filippo Castelnuovo, Carlo Torti.


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.

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. 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. 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.

Partial Text

The introduction of highly-active anti-retroviral therapy (HAART) has determined a dramatic improvement in the management of HIV-1 infection, leading to suppression of HIV viraemia and consequent restoration of the immune function. However, viro-immunological effectiveness of HAART may be hampered by other factors [1-4].

We studied a cohort of 3,262 patients, of whom 863 were positive for HCV Ab. Main characteristics of the population at baseline, stratified into 6 groups by HCV Ab status and type of anchor class (PI, PI/r, NNRTI), are shown in Table 1. In the whole population males were 73%, mean age was 37.2 years at cohort entry and was 39.1 years at HAART initiation. HCV Ab-positive patients were more likely to be younger and IVDU than HCV Ab-negative patients; AIDS events at baseline were more frequent in HCV Ab-negative patients.

In this study, the possible impact of HCV co-infection on viro-immunological effectiveness of different HAART regimens was explored both in the early and in the late follow-up and using both a stratified and a multivariable analysis.

Co-authors (CT, NB, EF, PN, FM, GC, SDG, MF, MDP, NL, LS, SC, FC) received grants from several Pharmaceutical Companies for participating to advisory board and scientific conferences but the received supports did not influence the content of this paper. Remaining co-authors: none to declare.

Study concept and design: CT, DM, NB. Acquisition of data: CT, DM, NB, EF, PN, FM, GC, SDG, MF, MDP, NL, LS, SC, FC. Analysis and interpretation of data: CT, DM, NB, EF. Drafting of the manuscript: CT, DM, NB. Critical revision of the manuscript for important intellectual content: EF, PN, FM, GC, SDG, MF, MDP, NL, LS, SC, FC. All authors read and approved the final manuscript.




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