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Background: Several serum markers reflecting extracellular matrix status have been correlated with liver fibrosis in non-HIV-infected patients with chronic hepatitis C infection. These indexes have been less examined in HIV/HCV-coinfected individuals., Objective: We aimed to evaluate the predictive value of serum markers for liver fibrosis in HIV-infected patients with chronic hepatitis C virus (HVC)., Methods: Serum levels of metalloproteinases 1 and 2 (MMP-1 and -2), tissue inhibitors of matrix metalloproteinases (TIMP-1), procollagen type III N-terminal peptide (PIIINP), and hyaluronic acid (HA) were measured in HIV-infected patients with chronic hepatitis C at the time of obtaining a liver biopsy and before the consideration of anti-hepatitis C therapy., Results: One hundred and nineteen consecutive HIV-HVC coinfected patients were included. TIMP-1 (r = 0.6; P < 0.001), TIMP-1/MMP-1 ratio (r = 0.5; P < 0.001), TIMP-1/MMP-2 ratio (r = 0.3; P < 0.001), MMP-2 (r = 0.2; P = 0.044), PIIINP (r = 0.4; P < 0.001), and HA (r = 0.5; P < 0.001) were positively and significantly correlated with the fibrosis stage. In the multivariate analysis, TIMP-1 (odds ratio [OR] = 1.004, 95% confidence interval [CI]: 1.002 to 1.006, P = 0.001) and HA >95 microg/dL (OR = 6.041, 95% CI: 1.184 to 30.816, P = 0.031) were independently associated with liver fibrosis. The area under the curve of score to discriminate mild (F0-F1) from significant (F2-F4) fibrosis in the received-operating analysis using the variables TIMP-1 and HA was 0.84, with a sensitivity of 72.9% and a specificity of 83.1%., Conclusion: TIMP-1 and HA were quite sensitive and specific for predicting the degree of liver fibrosis in HIV-infected patients with chronic hepatitis C. These parameters may become a noninvasive alternative to liver biopsy when the degree of liver fibrosis needs to be estimated.

Background: As a result of adverse events, a moderate rate of virologic response, and high costs associated with hepatitis C virus (HCV) therapy, finding early markers of sustained treatment response is a clinical priority. In the HCV-monoinfected population, a reduction >or=2 log in plasma HCV RNA at week 12 of therapy (early virologic response [EVR]) predicts a sustained virologic response (SVR). Few data are available in HIV/HCV-coinfected patients, however., Methods: A subanalysis of data from HIV/HCV-coinfected patients treated with pegylated interferon-alpha-2b (PEG, 100-150 mug/wk) or interferon-alpha-2b (IFN, 3 MIU 3 times per week) plus ribavirin (RBV, 800-1200 mg/d) was conducted in a randomized single-center clinical trial. The duration of treatment was 48 weeks (only 24 weeks for HCV genotype 2 or 3 with a baseline HCV RNA level <800,000 IU/mL)., Results: Ninety-five patients were randomized (43 assigned to IFN + RBV and 52 assigned to PEG + RBV). Eighty patients completed at least 12 weeks on therapy and were included in the EVR analysis. Thirty-five (43%) of them attained an SVR (56% and 30% of patients treated with PEG and IFN, respectively; P = 0.026). An EVR occurred in 55 (69%; 80% of PEG + RBV group and 56% of IFN + RBV group). Overall, 35 of 55 patients with an EVR were sustained responders, yielding a positive predictive value of 64% (70% in PEG + RBV arm and 55% in IFN + RBV arm). None of the patients who demonstrated an HCV RNA decline of <2 logs at week 12 reached an SVR (negative predictive value of 100%)., Conclusion: Our results confirm the utility of an EVR to predict the chance of the lack of an SVR in HIV/HCV-coinfected patients, particularly those treated with PEG.

Current treatment guidelines for HIV infection recommend a relatively late initiation of highly active antiretroviral therapy (HAART). Nevertheless, there is still a concern that immune recovery may not be as complete once CD4+ T cells have decreased below a certain threshold. This study addressed the long-term response of CD4+ T-cell counts in patients on HAART and analyzed the influence of baseline CD4+ T-cell counts, baseline viral load, and age. An observational analysis of evolution of CD4+ T cells in 861 antiretroviral therapy-naive chronic HIV-1-infected patients who started treatment consisting of at least 3 drugs in or after 1996 was performed. Patients were classified in 4 groups according to baseline CD4+ T cells: <200 cells/mm3, 200-349 cells/mm3, 350-499 cells/mm3, and >or=500 cells/mm3. The main outcome measures were proportion of patients with CD4+ T cells <200/mm3 and >500/mm3 at last determination and rate of CD4+ T-cell recovery. Patients were followed-up for a median of 173 weeks (interquartile range [IQR], 100-234). There were no differences in follow-up between the 4 groups. CD4+ T cells increased in the whole cohort from a median of 214 cells/mm3 (IQR, 90-355) to 499 cells/mm3 (IQR, 312-733) (P<0.001). Compared with the group with a baseline CD4+ T-cell count of >or=500/mm3, the relative risk of having a last determination of CD4+ T-cell counts >200 cells/mm3 was 0.79 (95% CI, 0.75-0.83), 0.92 (95% CI, 0.89-0.96) and 1 for baseline CD4+ T cells <200 cells/mm3, 200-349 cells/mm3, and 350-499 cells/mm3, respectively. The relative risk of having a last determination of CD4+ T-cell counts >500 cells/mm3 was 0.32 (95% CI, 0.27-0.39, P<0.001), 0.69 (95% CI, 0.60-0.79, P<0.001), and 0.94 (95% CI, 0.83-1.06, P=0.38) for baseline CD4+ T-cell counts <200 cells/mm3, 200-349 cells/mm3, and 350-0499 cells/mm3, respectively, compared with a baseline CD4+ T-cell count of >or=500 cells/mm3. The increase in CD4+ T cells from baseline was statistically significant and was maintained for up to 4 years of follow-up. This increase seemed to slow down after approximately 3 years and reached a plateau after 4-5 years of follow-up even in patients who achieved and maintained viral suppression in plasma. Long-term immune recovery is possible regardless of baseline CD4+ T-cell count. However, patients who start therapy with a CD4+ T-cell count <200 cells/mm3 have poorer immunologic outcome as measured by the proportion of patients with CD4+ T cells <200/mm3 or >500/mm3 at last determination. It seems that the immune recovery slows down after approximately 3 years of HAART and reaches a plateau after 4-5 years of HAART.

Introduction: Lipodystrophy (LD) represents an important problem for HIV-1-infected patients receiving highly active antiretroviral therapy (HAART), although its impact on quality of life (QoL) has not been properly studied., Design: Cross-sectional, nonrandomized, observational study performed on consecutive, clinically stable outpatients taking HAART for more than 1 year., Methods: Data on patients' characteristics, HIV-1 infection, treatment adherence and adverse effects, overall QoL measured by the Profil der Lebensqualität Chronischkranker (PLC), and the presence of LD defined by clinical criteria were assessed., Results: Eighty-four (56%) of 150 interviewed patients fulfilled criteria for LD. Patients with LD were older, had been taking antiretroviral treatment longer, and reported a poorer physical status than patients without LD. Surprisingly, LD itself was not found to influence overall QoL. However, homosexual patients, unemployed patients, and those patients undergoing current psychiatric treatment showed greater impairment on some of the QoL subscales related to psychological well-being if they suffered from LD., Conclusion: The impact of HIV-related LD on QoL depends on certain patient characteristics, rather than on the presence of LD itself.

Objective: To assess baseline variables able to predict neuropsychiatric side effects (NPSEs) associated with the initiation of an efavirenz (EFV)-containing regimen in HIV-1-infected patients., Design: Open-label, prospective, observational study., Methods: Consecutive HIV-1-infected outpatients in whom EFV was prescribed underwent a psychiatric interview. At baseline and at 2, 4, and 12 weeks, patients completed the Symptoms Check List-90-Revised (SCL-90-R), the Medical Outcome Study for HIV-positive patients (MOS-HIV), and a standardized questionnaire concerning potential NPSEs., Results: Preliminary data showed that discontinuation of EFV because of NPSEs occurred in 4 of 31 patients (13%). Patients who completed the follow-up showed a decrease in SCL-90-R total score (p =.004) and in several subscales such as Interpersonal Sensitivity (p =.009), Depression (p =.001), and Anxiety (p =.040), whereas no changes in MOS-HIV were observed. Having fewer years of education (p =.006), having fewer baseline central nervous symptoms (p =.000), reporting better baseline physical status (p =.013), and having higher baseline scores in the Heath Transition subscale of the MOS-HIV (p =.000) and in the Somatization subscale of the SCL-90-R (p =.002) were associated with more NPSEs., Conclusion: Patients maintained on EFV showed a decrease in psychologic distress related to self-image, depression, and anxiety, without any effect on quality of life. Patients with a lower level of education, those who feel physically and psychologically better at baseline than in the past, and those who suffer from more distress as a result of physical complaints may be at greater risk of reporting more NPSEs after EFV initiation.