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.

NCT01900015.

Background In the LATTE-2 phase IIb study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with HIV-1. Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over ~5 years. Methods After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period. In the extension period through Week 256, participants continued their current LA regimen (randomized Q8W/Q4W groups) or switched from oral ART to Q8W or Q4W LA therapy (extension-switch groups). Endpoints assessed included proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot algorithm) and adverse events (AEs). Results At Week 256, 186 (81%) of 230 participants in randomized Q8W/Q4W groups and 41 (93%) of 44 participants in extension-switch groups had HIV-1 RNA <50 copies/mL. No protocol-defined virologic failures occurred after Week 48. Injection-site reactions infrequently resulted in discontinuation (4 [2%] and 1 [2%] participants in randomized Q8W/Q4W and extension-switch groups, respectively). Three participants in randomized Q8W/Q4W groups experienced drug-related serious AEs, including 1 fatal serious AE (Q4W group); none occurred in extension-switch groups. Of 25 participants with AEs leading to withdrawal, 20 were in the randomized Q4W group; no AE leading to withdrawal occurred in >1 participant. Conclusions Cabotegravir + rilpivirine LA exhibited long-term efficacy and tolerability, demonstrating its durability as maintenance therapy for HIV-1 infection (ClinicalTrials.gov, NCT02120352).

BackgroundIn patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.MethodsIn this observational, cross-sectional study we included patients with plasma virological suppression (≥1 year) without concomitant major neurocognitive confounders, currently receiving for ≥1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed.ResultsOf the 191 included patients - triple therapy: 96, 1–2 years of monotherapy: 40 and >2 years of monotherapy: 55 - proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9–33.6); triple therapy, 31.6% (22.1–41.0); short-term monotherapy, 25.0% (11.3–38.7); long-term monotherapy: 21.4% (10.5–32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29–2.50) and for long-term monotherapy 0.40 (0.14–1.15).ConclusionsCompared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.

The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia.

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.

IntroductionEmotional processing is basic for social behaviour. We examine for the first time the facial emotion processing in long-term HIV-suppressed patients.Materials and MethodsCross-sectional study comparing (ANOVA) six facial emotional processing tasks (two discrimination, two memory and two recognition) between HIV-suppressed patients (HIV+) on effective antiretroviral therapy (>2 years) and matched (age, gender) healthy controls (HCs). Accuracy in the recognition of basic emotions (neutral, happiness, sadness, anger and fear) in each recognition task was also compared (Mann–Whitney U test) between HIV+ and HCs. In the subset of HIV+, we evaluate which factors were associated with impaired recognition of basic emotions (accuracy below 50%) by multiple logistic regression analysis. Overall performance in all six emotional tasks were separately compared between neurocognitive impaired and non-impaired HIV+.ResultsWe included 107 HIV+, mainly Caucasian (89%) male (72%) with a mean age of 47.4 years, neurocognitively non-impaired (75.5%), and 40 HCs. Overall discrimination (p=0.38), memory (p=0.65) and recognition tasks (p=0.29) were similar in both groups. However, HIV+ had lower sadness recognition in both recognition tasks and lower sadness, anger and fear recognition in the facial affect selection task (Figure 1). Only estimated pre-morbid functioning (WAIS-III-R vocabulary subtest score) was significantly associated with sadness (1.99 [95% CI 1.18–3.58]; p=0.01) and anger recognition deficits (2.06 [95% CI 1.14–3.45]; p=0.015) in the facial affect selection task. In HIV+ individuals, neurocognitive impairment was associated with worse memory task results (p<0.01, d=0.88; p<0.01, d=1.48). ConclusionsWe did not find difference in the overall emotion processing between HIV+ and HIV- individuals. However, we found particular recognition deficits in the entire HIV+ sample. Estimated pre-morbid functioning was associated with sadness and anger recognition deficits in the facial affect selection task. Neurocognitive impaired HIV+ had additional memory deficits. These recognition deficits might conduct to social difficulties.

Background & Aims Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with Child‐Turcotte‐Pugh (CTP) score and hepatic decompensation in HIV/HCV‐coinfected and HCV‐monoinfected patients with advanced cirrhosis. Methods A cross‐sectional study was carried out in 62 HIV/HCV‐coinfected and 28 HCV‐monoinfected patients. Metabolomics analysis was performed by gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography‐mass spectrometry (LC‐MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS‐DA) and generalized linear model (GLM) with binomial distribution (to analyse HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyse different stages of cirrhosis (CTP score). Results The statistical analysis identified plasma metabolites associated with HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulphur amino acids, butyrate derivatives, oxidized phospholipids, energy‐related metabolites and bacterial fermentation‐related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched‐chain amino acids (BCAA) and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV‐ and HCV‐infected patients. Glycolic acid, LPC (16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥ 7). Conclusion Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV‐coinfected and HCV‐monoinfected patients.