Search

To determine risk factor for non-AIDS severe clinical events in HIV-infected patients on long-term combination antiretroviral therapy (cART).A validation committee reviewed each severe clinical event that occurred in the APROCO/COPILOTE (ANRS CO8) cohort that enrolled 1281 patients in 1997-1999 at the initiation of cART containing protease inhibitor. Probability of the occurrence of a first non-AIDS, cART-related, and AIDS-defining event was estimated, and potential determinants were studied using Cox regression models.During a median follow-up of 7.3 years, the incidence of non-AIDS events was higher than that of cART-related and AIDS-defining events (10.5, 3.6, and 2.6 per 100 patient-years, respectively). Bacterial (mainly airway) infections were the most frequent non-AIDS events (23.4%) followed by non-AIDS-defining malignancies and cardiovascular events (both 9.5%). Factors independently associated with the occurrence of a first non-AIDS event were age60 years [hazard ratio (HR) 2.1; 95% confidence interval (CI): 1.3 to 3.2] and CD4100 cells per milliliter (HR 2.5; 95% CI: 1.8 to 3.6) but also plasma HIV RNA4 log10 copies per milliliter at the time of the event (HR 1.9; 95% CI: 1.5 to 2.5).Optimization and permanent continuation of long-term antiretroviral therapy in HIV-infected patients is the best strategy to prevent or reduce the occurrence of non-AIDS severe morbidity.

The factors that determine the emergence of X4 isolates in some HIV-1-infected subjects are unknown. As the level of expression of CXCR4 could favor an R5 to X4 switch, quantitative flow cytometry was used to measure CXCR4 density on CD4 T cells in 200 HIV-1-positive adults, and this was compared with CD4 counts, interleukin-7 (IL-7), and RANTES (regulated on activation, normal T expressed and secreted) plasma levels and the R5/X4 virus phenotype. CD4 T-cell surface CXCR4 densities were increased in infected subjects and inversely correlated with CD4 T-cell count (r=-0.548, P0.001). Yet, in vitro infection with either R5 or X4 strains and in vivo increases in viral load following interruption of antiretroviral treatment did not induce CXCR4 overexpression. The plasma levels of IL-7 and RANTES, 2 cytokines able to induce CXCR4 expression, did not correlate with CXCR4 density. Finally, higher CXCR4 densities were observed in patients harboring X4 strains (3300, 95% CI 2431-4169 CXCR4 molecules per cell) than in patients harboring only R5 strains (2406, 95% CI 2135-2677, P=0.027). These data suggest that CXCR4 overexpression during the course of the disease in some patients could favor the emergence of X4 strains.

CCR5 antagonists represent promising anti-HIV agents. Yet, if the CCR5 chemokine receptor plays a positive role in hepatitis C virus (HCV) infection, CCR5 antagonists might be contraindicated in HCV/HIV-coinfected subjects. Therefore, we tested the hypothesis that the level of T-cell surface CCR5 expression, which might determine the intensity of HCV-specific T-cell recruitment into the liver, and thereby the efficiency of the anti-HCV response, could determine HCV disease evolution. For this purpose, we compared CCR5 density, measured by quantitative flow cytometry at the surface of nonactivated (human leukocyte antigen-D-related [HLA-DR]-) T cells of 51 HCV/HIV patients, with HCV load, serum aminotransferase levels, and liver histology (inflammatory activity, fibrosis, and rate of fibrosis progression). DR-CD4+ T-cell surface CCR5 density, which correlated with DR-CD8+ T-cell surface CCR5 density and was stable over time in HCV/HIV-coinfected individuals, did not correlate with any of the biologic parameters of HCV infection analyzed and was not linked to the capacity to clear the virus. In conclusion, we failed to demonstrate any impact of interindividual variability in T-cell surface CCR5 density on HCV infection, which would have argued against the use of CCR5 antagonists in HIV/HCV-coinfected subjects.