Background. Sustained virological response (SVR) after therapy with interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). We assessed the effect of SVR on HIV progression and mortality not related to liver disease. Methods. An observational cohort study including consecutive HIV/HCV-coinfected patients treated with interferon plus ribavirin between 2000 and 2008 in 19 centers in Spain. Results. Of 1599 patients, 626 (39%) had an SVR. After a median follow-up of approximately 5 years, we confirmed that failure to achieve an SVR was associated with an increased risk of liver-related events and liver-related death. We also observed higher rates of the following events in nonresponders than in responders: AIDS-defining conditions (rate per 100 person years, 0.84 [95% confidence interval (CI), .59–1.10] vs 0.29 [.10–.48]; P= .003), non–liver-related deaths (0.65 [.42–.87] vs 0.16 [.02–.30]; P = .002), and non–liver-related, non–AIDS-related deaths (0.55 [.34–.75] vs 0.16 [.02–.30]; P = .002). Cox regression analysis showed that the adjusted hazard ratios of new AIDS-defining conditions, non–liver-related deaths, and non–liver-related, non–AIDS-related deaths for nonresponders compared with responders were 1.90 (95% CI, .89–4.10; P = .095), 3.19 (1.21–8.40; P = .019), and 2.85 (1.07–7.60; P = .036), respectively. Conclusions. Our findings suggest that eradication of HCV after therapy with interferon plus ribavirin in HIV/HCV-coinfected patients is associated not only with a reduction in liver-related events but also with a reduction in HIV progression and mortality not related to liver disease.

Objectives: The aim of this study was to evaluate the frequency, characteristics and risk factors of lipid changes associated with lopinavir/ritonavir treatment in antiretroviral-naive patients. Methods: A prospective cohort of 107 antiretroviral-naive HIV-infected patients was followed for 12 months after starting lopinavir/ritonavir-based highly active antiretroviral therapy. Results: At 12 months, percentages of patients with hypercholesterolaemia and hypertriglyceridaemia were 17.4% and 40%, respectively. Mean increases in total cholesterol and triglycerides were 40.7 and 73.3 mg/dL. There was a significant increase in both low-density and high-density (HDL) cholesterol, and no increase in the total cholesterol/HDL ratio (from 4.16 at baseline to 4.49 after 12 months). Baseline cholesterol > 200 mg/dL and triglycerides > 150 mg/dL were independent risk factors for dyslipidaemia, while hepatitis C coinfection appeared to be protective. Conclusions: Patients with elevated lipid values at baseline have the greatest risk of developing hypercholesterolaemia and hypertriglyceridaemia after starting lopinavir/ritonavir. Antiretroviral-naive patients coinfected with hepatitis C have a low risk of developing hyperlipidaemia after starting lopinavir/ritonavir.

Introduction: Few clinical trials and cohort studies have evaluated the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV (PWH) with preexisting M184V/I or other nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs). Real-world data are also scarce. Methods: Retrospective review of treatment-experienced patients who started B/F/TAF in a cohort of PWH. HIV-RNA less than 50 copies/ml was analyzed at 48 weeks in an intention-to-treat (ITT) analysis (missing=failure) and per protocol analysis (patients with missing data or changes for reasons other than virological failure were excluded). Results were compared in patients with and without previous NRTI-RAMs. Results: Five hundred and six PWH were included (16.2% women). Median age and time with HIV infection were 52.3 and 18.9 years, respectively. At baseline, viral load was less than 50 copies/ml in 440 patients (86.6%). Overall, 69 (13.6%) participants had documented preexisting NRTI-RAMs: 57 (11.2%) M184V/I and 30 (5.9%) tenofovir RAMs. In the ITT analysis, 83% (420/506) had HIV-RNA less than 50 copies/ml [82.2% (359/437) and 88.4% (61/69) in persons without and with NRTI-RAMs, respectively (P = 0.2)]. In the per protocol analysis 94.2% (420/445) had HIV-RNA less than 50 copies/ml [94.4% (359/380) vs. 93.8% (61/65); P = 0.2]. A total of 61 participants were excluded from the per protocol analysis (23 missing data, 19 discontinued B/F/TAF because of toxicity, 13 for other reasons, and 6 died). Conclusion: Switching to B/F/TAF is well tolerated and effective in the real-world setting, even in patients with preexisting NRTI RAMs, such as M184V and RAMs conferring resistance to tenofovir. These results confirm the robustness of this combination.

Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 - 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients.

Background: Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4⁺ T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liver stiffness measure (LSM)] and their linear relationship. Methods: We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had 25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results: We found HIV/HCV-coinfected patients had higher values of CD4⁺ Tregs (p < 0.001), memory Tregs (p ≤ 0.001), and plasma cytokine levels [IFN-γ (p ≤ 0.05) and IL-10 (p ≤ 0.01)] compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83; p = 0.019), IL-2 (aAMR = 0.78; p = 0.017), TNF-α (aAMR = 0.67; p < 0.001), and IL-17A (aAMR = 0.75; p = 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66; p = 0.021), TNF-α (aAMR = 0.565; p = 0.003), and IL-17A (aAMR = 0.58; p = 0.003) than patients with <12.5 kPa. Conclusion: HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response.