Changes in Liver Steatosis After Switching From Efavirenz to Raltegravir Among Human Immunodeficiency Virus-Infected Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND: Antiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues. METHODS: HIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues. At baseline, eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m. Changes in hepatic steatosis at 48 weeks of follow-up over baseline levels were measured by CAP. RESULTS: Overall, 39 patients were included, and 19 of them were randomized to switch to RAL. At week 48, median CAP for the RAL group was 250 (Q1-Q3, 221-277) dB/m and 286 (Q1-Q3, 269-314) dB/m for the EFV group (P = .035). The median decrease in CAP values was -20 (Q1-Q3, -67 to 15) dB/m for the RAL arm and 30 (Q1-Q3, -17 to 49) dB/m for the EFV group (P = .011). CAP values <238 dB/m at week 48 were observed in 9 (47%) patients on RAL and 3 (15%) individuals on EFV (P = .029). CONCLUSIONS: After 48 weeks, HIV-infected individuals switching EFV to RAL showed decreases in the degree of hepatic steatosis, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant hepatic steatosis after 48 weeks was greater for those who switched to RAL. CLINICAL TRIALS REGISTRATION: NCT01900015.

Impact of liver steatosis on the correlation between liver stiffness and fibrosis measured by transient elastography in patients coinfected with human immunodeficiency virus and hepatitis C virus.

We assessed the effect of different hepatic conditions such as fibrosis, steatosis and necroinflammatory activity on liver stiffness as measured by transient elastography in HIV/HCV-coinfected patients. We studied all consecutive HIV/HCV-coinfected patients who underwent liver biopsy and elastography between January 2007 and December 2008. Liver fibrosis was staged following METAVIR Cooperative Study Group criteria. Steatosis was categorized according to the percentage of affected hepatocytes as low (≤10%), moderate (<25%) and severe (≥25%). A total of 110 patients were included. Fibrosis was distributed by stage as follows: F0, n = 13; F1, n = 47; F2, n = 29; F3, n = 18; and F4, n = 3. Liver biopsy revealed the presence of hepatic steatosis in 68 patients (low to moderate, n = 53; and severe n = 15). By univariate regression analysis, fibrosis, necroinflammatory activity, and the degree of steatosis were correlated with liver stiffness. However, in a multiple regression analysis, steatosis and fibrosis were the only independent variables significantly associated with liver stiffness. With a cut-off of 9.5 kPa to distinguish patients with F ≤ 2 from F ≥ 3, elastography led to a significantly higher number of misclassification errors (25%vs 5%; P = 0.014), most of which were false positives for F ≥ 3. Our study suggests that the correlation between liver stiffness and fibrosis as estimated by transient elastography may be affected by the presence of hepatic steatosis in HIV/HCV-coinfected patients.

Comparison of transient elastography and liver biopsy for the assessment of liver fibrosis in HIV/hepatitis C virus-coinfected patients and correlation with noninvasive serum markers.

Transient elastography (FibroScan) is a novel, rapid and noninvasive technique to assess liver fibrosis. Our objective was to compare transient elastography (TE) and other noninvasive serum indexes as alternatives to liver biopsy in HIV/hepatitis C virus (HCV)-coinfected patients. The fibrosis stage (METAVIR Score), TE, the aspartate aminotransferase-to-platelet ratio index, the Forns fibrosis index, FIB-4 and HGM-2 indexes were assessed in 100 patients between January 2007 and January 2008. The diagnostic values were compared by calculating the area under the receiver operating characteristic curves (AUROCs). Using TE, the AUROC (95% CI) of liver stiffness was 0.80 (0.72-0.89) when discriminating between F 2, 0.93 (0.85-1.00) when discriminating between F 3 and 0.99 (0.97-1.00) when discriminating between F or= 3, the AUROCs of TE were significantly higher than those obtained with the other four noninvasive indexes. Based on receiver operating characteristic curves, three cutoff values were chosen to identify F or= 3 (>or=11 kPa) and F4 (>or=14 kPa). Using these best cutoff scores, the negative predictive value and positive predictive value were 81.1% and 70.2% for the diagnosis of F or= 3 and 100% and 57.1% for the diagnosis of F4. Thus, Transient elastography accurately predicted liver fibrosis and outperformed other simple noninvasive indexes in HIV/HCV-coinfected patients. Our data suggest that TE is a helpful tool for guiding therapeutic decisions in clinical practice.

Facial Emotion Processing in Aviremic HIV-infected Adults.

The emotional processing in human immunodeficiency virus-seropositive individuals (HIV+) has been scarcely studied. We included HIV+ individuals (n = 107) on antiretroviral therapy (≥2 years) who completed 6 facial processing tasks and neurocognitive testing. We compared HIV+ and healthy adult (HA) participants (n = 40) in overall performance of each facial processing task. Multiple logistic regressions were conducted to explore predictors of poorer accuracy in those measures in which HIV+ individuals performed poorer than HA participants. We separately explored the impact of neurocognitive status, antiretroviral regimen, and hepatitis C virus (HCV) coinfection on the tasks performance. We found similar performance in overall facial emotion discrimination, recognition, and recall between HIV+ and HA participants. The HIV+ group had poorer recognition of particular negative emotions. Lower WAIS-III Vocabulary scores and active HCV predicted poorer accuracy in recognition of particular emotions. Our results suggest that permanent damage of emotion-related brain systems might persist despite long-term effective antiretroviral therapy.

[Retrospective epidemiological study on the durability of the treatment of HIV infection or AIDS in Spain]. / Estudio epidemiológico retrospectivo sobre la duración del tratamiento de la infección por el virus de la inmunodeficiencia humana en España.

BACKGROUND AND OBJECTIVE: To know the durability of consecutive regimens of antiretroviral treatment is important to design a long-term therapy, but there is not much information about this subject. PATIENTS AND METHOD: Retrospective epidemiological study of a sample of 401 patients who began antiretroviral treatment between January 1997 and April 2000 at ten Spanish hospitals. The duration of each consecutive antiretroviral regimen was calculated and the reasons for modification and discontinuation were described. RESULTS: In the 3 years and 3 months covered by the study, 48.6% of the patients received more than one regimen of therapy. Seventy five of the initial prescribed combinations included protease inhibitors. Median duration of consecutive lines of therapy was decreasing: 560, 360, 330 and 202 days for the first, second, third and fourth regimens, respectively. The main reason to modification was intolerance or toxicity (46.2, 49.1 and 47.1% for the first, second and third modification). A fifth of changes was originated by difficulties to follow the therapy. Virological failure was the reason for modification in 21.8, 24.5 and 26.5% of first, second and third changes. CONCLUSIONS: Duration of consecutive antiretroviral regimens progressively decreases. Intolerance or drug toxicity were the main reasons conditioning the change of treatment.

Safety and efficacy of an induction dose of pegylated interferon alpha-2a on early hepatitis C virus kinetics in HIV/HCV co-infected patients: the CORAL-1 multicentre pilot study.

To evaluate the safety and efficacy of an induction dose of pegylated interferon alpha 2a (IFN-alpha2a) on the 12-week hepatitis C virus (HCV) kinetics in human immunodeficiency virus (HIV) patients co-infected with HCV. One hundred sixteen HIV/HCV co-infected patients from nine hospitals in Spain were randomized to receive 270 microg/week of pegylated IFN-alpha2a for 4 weeks followed by 180 microg/week for 8 weeks or 180 microg/week for 12 weeks. Ribavirin was given at a daily dose of 1000 or 1200 mg. The main outcome measure was the percentage of patients achieving an HCV-RNA below 50 IU/mL or a decrease of 2 or more log(10) at week 12 (early virologic response, EVR). HCV-RNA was measured at baseline, weekly, for the first 4 weeks and monthly thereafter. We observed no difference in the percentage of patients achieving an EVR between arms (on-treatment, 74% in both arms; intention-to-treat, 70% in the induction arm and 67% in the control arm), nor were there differences in the percentage achieving an undetectable HCV qualitative polymerase chain reaction at any time points or in the decrease in HCV-RNA from baseline. No differences were found between arms in the percentage of dropouts (8% in the whole study population). Our study failed to find a benefit of an induction dose of 270 microg/week of pegylated IFN-alpha2a for 4 weeks on the EVR in co-infected patients who are treatment naive. Despite the lack of benefit with this regimen, induction therapy with this schedule was safe and well tolerated in co-infected patients.

[Report of three cases of hyperlactacidemiae/lactic acidosis after treatment of hepatitis C with pegylated interferon and ribavirin in HIV coinfected patients]. / A propósito de tres casos de hiperlactacidemia/acidosis láctica tras el tratamiento de la hepatitis C con interferón pegilado y ribavirina en pacientes coinfectados por VIH.

The hepatitis C infection is highly prevalent among HIV-infected patients. As a direct consequence of the increased survival of these patients in the HAART era, liver disease and its long-term complications have became a genuine health problem in these patients. The treatment of chronic HCV hepatitis is associated with several secondary effects, hiperlactacidemiae/lactic acidosis is one of the most dangerous. It appears to be related with the association of ribavirin and ddI, d4T or AZT. These are three cases of hiperlactacidemiae/lactic acidosis collected during the first twelve months of treatment with pegylated interferon and ribavirin in University Hospital of Guadalajara.