However, other studies found that HIV-1/HCV-coinfected patients had worse clinical outcomes, in terms of either progression to AIDS or death, than HIV-1-monoinfected patients [4–6,16–21]. In this regard, some authors also observed that the negative impact on survival was not caused by a difference in CD4 cell count [19], and that deaths and hospitalizations in HCV-infected patients were primarily for non-AIDS-defining infections and complications PLX4032 mouse of IDU [2]. These findings suggest that cofactors independent of HIV-1 disease itself condition this worse outcome. However, Klein et al., who retrospectively compared the development of opportunistic infections, deaths and hospitalizations before and after the

introduction of combination ART, found that coinfected patients experienced no clear benefit from ART, not showing the rate reductions for all outcomes experienced by HIV-1-monoinfected patients [2]. Interestingly, a study on 207 HIV-1/HCV-coinfected patients followed up for 7 years that analysed the influence

of HCV viral load on clinical HIV-1 outcomes found that, after controlling for CD4 cell count and HIV-1 viral load, every 10-fold increase in baseline HCV RNA was associated with higher relative risks EPZ-6438 research buy of progression to AIDS and AIDS-related mortality [17]. Regarding immunological outcomes, multiple studies have analysed CD4 responses to ART in patients with or without HCV infection, also with contradictory results. Some studies found that HCV coinfection did not influence such responses [3,18–32]. However, others

found trends towards lower CD4 cell counts in coinfected patients [3,25], and others reported no effect in the overall study group, but a significant effect in the subset of patients with CD4 counts >600 cells/μL [21]. One study found a delayed CD4 cell count recovery at 4 weeks in patients coinfected with HCV or HBV that disappeared at 48 weeks [26], and another also found lower initial CD4 responses, a difference that disappeared at 4 years [10]. Some authors even found more robust immune restoration among HIV-1/HCV/HBV triply coinfected subjects who developed liver enzyme elevation after ART initiation [38]. Similarly, others observed that the CD4 cell percentages were slightly higher in HIV-1/HCV-coinfected than in HIV-1-monoinfected Metformin molecular weight women [33]. Regarding ART-untreated patients, a study reported no deleterious effect of HCV infection on the progression of long-term nonprogressors [35], and another that CD4 cell count decline did not differ between HIV-1-monoinfected and coinfected patients following interruption of ART [34]. In contrast, other studies found poorer responses in coinfected patients [3–15]. In some of these studies, it was found that HCV infection was associated with lower CD4 cell counts in patients who were adherent to ART, but not in those not adherent or not taking ART [8].