Weight gain in HIV-infected patients.

Since its emergence, HIV has been linked to metabolic alterations with an impact on the distribution of fat and the weight of people living with HIV. While extreme weight loss and processes such as lipodystrophy were of concern at first, in recent years, and with the appearance of increasingly effective and better tolerated drugs, an abnormal weight gain is paradoxically taking place among people living with HIV. Although this weight gain is a multifactorial process in which lifestyle habits, physical exercise or diet have a great impact, antiretroviral treatment has been recently considered as one of the key causes of this increase according to different clinical trials and real-life cohorts. The use of integrase inhibitors, specifically dolutegravir or bictegravir, and being female and/or from African/American origin appear to contribute to weight gain. In contrast, drugs such as tenofovir disoproxil fumarate would be protective factors. Even though different mechanisms of action have been proposed by which these agents would cause weight gain, the exact processes remain unclarified. Efforts are currently focused on knowing not only these mechanisms, but, more importantly, on finding the clinical relevance that this abnormal weight gain could have in other pathologies such as diabetes or cardiovascular events.

Progress in the quality of care for newly diagnosed people with HIV in Spain (2004-2019).

BACKGROUND: We monitored the quality of care for newly diagnosed people with HIV (PWH) in Spain, including linkage to care within 1 month of HIV diagnosis (LC-1Mo) and viral suppression within 3 months of HIV diagnosis (VS-3Mo). METHODS: Longitudinal study based on The Cohort of the Spanish AIDS Research Network (CoRIS). We used logistic regression stratified by year of HIV diagnosis (2004-2013 and 2014-2019) to assess differences by sex, country of origin, HIV risk group, age, prior AIDS, HIV Viral Load, and CD4 cell count. RESULTS: The final analysis included 13,632 PWH: males 85%, men having sex with men (MSM) 61%, median age 35 years. LC-1Mo increased from 42% (95% CI, 38%-46%) in 2004 to 80% (95% CI, 77%-83%) in 2019 (P < 0.001). Median CD4+ cell counts at ART initiation increased from <250/mm3 in 2004-2005 to >350/mm3 since 2012 (P < 0.001). The percentage of initial regimens based on integrase strand transfer inhibitors (INSTI) increased from 3% in 2004 to >70% from 2016 onwards (P < 0.001). VS-3Mo increased from 6% (95% CI, 4%-8%) in 2004 to 45% (95% CI, 41%-49%) in 2019 (P < 0.001). Worst results for LC-1Mo were found among PWH acquiring HIV by injection drug use and those born in Latin American Countries across all the study period. CONCLUSION: Care indicators have improved among newly diagnosed PWH in Spain over the last 15 years. Removal of CD4 cell counts limitations, and probably the increasing use of INSTI-based regimens was decisive for the progress made.

Down-Regulation of the Longevity-Associated Protein SIRT1 in Peripheral Blood Mononuclear Cells of Treated HIV Patients.

The activity of sirtuin 1 (SIRT1), a class III histone deacetylase with a critical role in several biological functions, decreases with age and its deficiency is associated with many inflammatory and age-related diseases. It also regulates the chronic immune activation and viral latency during an HIV infection. The life-span and particularly the health span of HIV patients are substantially shortened; however, the participation of SIRT1 in these effects is not clear. We performed a prospective cross-sectional monocentric study that included 70 HIV-infected patients and 43 BMI-, age- and sex-matched uninfected individuals. We found that in the PBMCs of the HIV patients, SIRT1 mRNA levels were significantly lower (p < 0.0001). This decrease, which was corroborated at the protein level, occurred irrespectively of the antiretroviral regimen these patients received and was not significantly related to the general, HIV-related or comorbidity-related parameters. The levels of the major mitochondrial sirtuin SIRT3 were not altered. Moreover, the strong correlations of SIRT1 with the leukocyte markers CD8A and CD19 present in the uninfected individuals were absent in the HIV patients. In conclusion, this study showed that the PBMCs of the HIV patients displayed diminished SIRT1 levels and altered correlations of SIRT1 with markers of CD8+ T cells and B cells, findings which may be relevant for understanding the complex pathogenic milieu in HIV patients.

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019.

OBJECTIVES: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. METHODS: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. RESULTS: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). CONCLUSIONS: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.

The Experience With Health Care of Patients With Inflammatory Arthritis: A Cross-sectional Survey Using the Instrument to Evaluate the Experience of Patients With Chronic Diseases.

BACKGROUND: Patients' experience with health care is becoming a key component for the provision of a patient-centered health care model. The aim of this study was to assess the experience with health care of patients with inflammatory arthritis and patient- and health care-related factors. METHODS: Patients responded to an anonymous survey provided by their treating clinical teams. The survey comprised the validated 12-item IEXPAC (Instrument to Evaluate the EXperience of PAtients with Chronic diseases) tool and demographic variables and health care-related characteristics that may affect patients' experience. RESULTS: A total of 359 of 625 surveys were returned (response rate, 57.4%). Overall, patient responses were positive (>60% gave "always/mostly" answers) for statements assessing the interaction between patients and health care professionals or patient self-management following health care professional guidance. However, positive patient responses for items regarding patient interaction with the health care system via the internet or with other patients were less than 13%. Only 25.6% of patients who had been hospitalized reported receiving a follow-up call or visit following discharge. In the bivariate analysis, experience scores were higher (better experience) in men, those seen by fewer specialists or by the same physician, and in patients treated with a fewer number of drugs or with subcutaneous/intravenous drugs. Multivariate analyses identified regular follow-up by the same physician and treatment with subcutaneous/intravenous drugs as variables associated with a better patient experience. CONCLUSIONS: This study identifies areas of care for patients with inflammatory arthritis with the potential to improve patients' experience and highlights the importance of patient-physician relationships and comprehensive patient care.

Effects of Hepatitis C Virus (HCV) Eradication on Bone Mineral Density in Human Immunodeficiency Virus/HCV-Coinfected Patients.

BACKGROUND: Little is known about the effects of eradication of hepatitis C virus (HCV) on bone mineral density (BMD) and biomarkers of bone remodeling in human immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We prospectively assessed standardized BMD (sBMD) at the lumbar spine and femoral neck, World Health Organization BMD categories at both sites, and plasma concentrations of soluble receptor activator of NF-κß ligand (sRANKL), and osteoprotegerin (OPG) at baseline (the date of initiation of anti-HCV therapy) and at 96 weeks. RESULTS: A total of 238 patients were included. The median age was 49.5 years, 76.5% were males, 48.3% had cirrhosis, 98.3% were on antiretroviral therapy, median CD4+ cell count was 527 cells/µL, and 86.6% had HIV-1 RNA <50 copies/mL. The prevalence of osteoporosis at baseline at the lumbar spine (LS) and femoral neck (FN) was 17.6% and 7.2%, respectively. Anti-HCV therapy comprised pegylated interferon (peg-IFN) and ribavirin (RBV) plus 1 direct-acting antiviral in 53.4%, peg-IFN/RBV in 34.5%, and sofosbuvir/RBV in 12.2%. A total of 145 (60.9%) patients achieved sustained virologic response (SVR). No significant effect of SVR was observed on sBMD for the interaction between time and SVR either in the LS (P = .801) or the FN (P = .911). Likewise, no significant effect of SVR was observed in plasma levels of sRANKL (P = .205), OPG (P = .249), or sRANKL/OPG ratio (P = .123) for the interaction between time and SVR. No significant correlation was found between fibrosis by transient elastography, and LS and FN sBMD, at baseline and week 96. CONCLUSIONS: SVR was not associated with significant changes in BMD nor biomarkers of bone remodeling in HIV/HCV-coinfected persons.

Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

p53 and p53-related mediators PAI-1 and IGFBP-3 are downregulated in peripheral blood mononuclear cells of HIV-patients exposed to non-nucleoside reverse transcriptase inhibitors.

The improved effectiveness and safety of the combined antiretroviral therapy (cART) has largely diminished mortality and AIDS-defining morbidity of HIV-patients. Nevertheless, chronic age-related diseases in these individuals are more common and their underlying pathogenic mechanisms of these actions seem to involve accelerated aging and enhanced inflammation. The present study explores markers of these processes in a heterogenous Spanish HIV cohort using peripheral blood samples of HIV-patients and matched uninfected controls. We isolated periheral blood mononuclear cells (PBMCs) and i) compared the expression of a panel of 14 genes related to inflammation and senescence in PBMCs of HIV-patients vs matched uninfected controls, ii) analyzed the expression in HIV-patients in association with a number of demographic, biochemical and immunological parameters and iii) in relation with the current cART they received. PBMCs of HIV-patients displayed significantly increased expression of general inflammatory genes (IL6, IL18 and CXCL10) and this occurs irrespectively of the antiviral therapy they have been receiving. Conversely, levels of senescence-associated genes TP53, SERPINE1andIGFBP3 were slightly but significantly reduced in patients compared to uninfected matched individuals and this effect is related to NNRTI-containing treatments. The expression of the inflammatory markers IL6, IL18, IL1B, TNFA, RELA, CCL2, CCL20 and CXCL10 displayed correlation with certain demographic, morbidity- and HIV infection-related parameters. The levels of TP53 mRNA were positively associated only with plasma LDL. Correlation analysis between the expressions of pairs of genes revealed a different pattern between HIV-patients and controls. The diminished expression of TP53 and SERPINE1 in HIV-patients was also observed at a protein level, and the correlation between the two proteins (p53 and PAI1) in patients and controls showed the opposite trend. In conclusion, HIV-patients show dysregulation of p53 and p53-related mediators, a phenomenon which may be of pathophysiological relevance and could be related to the shorter health- and/or life-span observed in these individuals.

Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21.

The incidence of classical Hodgkin lymphoma (cHL) in the HIV-1 setting has increased 5-25-fold compared to that observed in the general population. This study aimed to determine whether selected micro RNAs (miRs) and other soluble biomarkers and cellular subsets are dysregulated in cHL and could be used as biomarkers. This was a retrospective and longitudinal matched case-control study of 111 Caucasian, HIV-1-infected adult individuals, including 37 individuals with cHL and 74 with no type of cancer. Immunovirological data, plasma exosome-derived miR-16, miR-20a, miR-21, miR-221, miR-223, miR-106a, miR-185, miR-23, miR-30d, miR-222, miR-146a and miR-324, plasma IL-6, sCD14, sCD27, sCD30, sIL-2R, TNFR1, and cell phenotyping of T and B lymphocytes and natural killer (NK) cells were analyzed. Before cHL diagnosis, miR-20a, miR-21, and sCD30 were higher in cHL (p = 0.008, p = 0.009 and p = 0.042, respectively), while miR-16 was down-regulated (p = 0.040). miR-20a and miR-21 were independently associated with cHL (p = 0.049 and p = 0.035, respectively). The combination of miR-20a and miR-21 showed a good AUC value of 0.832 with a moderate likelihood ratio positive (LR+) value of 5.6 and a slight likelihood ratio negative (LR-) value of 0.23. At cHL diagnosis, miR-20a, miR-21 and miR-324 were overexpressed in cHL (p = 0.005, p = 0.024, and p = 0.001, respectively), while miR-223, miR-16, miR-185 and miR-106a were down regulated (p = 0.042, p = 0.007, p = 0.006, and p = 0.002, respectively). In addition, sCD14, sCD27, sCD30 and IL2R levels were higher in these individuals (p = 0.038, p = 0.010, p = 0.030, p = 0.006, respectively). miR-20a was independently associated with cHL (p = 0.011). The diagnostic value of miR-20a showed good AUC value of 0.754 (p = 0.074) with a slight LR+ value of 2 and a slight LR- of 0.25. After chemotherapy, miR-20a was higher in those individuals who had an adverse outcome (p < 0.001), while sCD14 and sCD30 were higher (p < 0.001). A specific signature of miRs and cytokines associated with a subsequent cHL diagnosis was found in this study, especially miR-20a and miR-21. Also, another biomarker signature was found at cHL diagnosis, with a relevant discriminant disease value for miR-20a. Of note, miR-20a expression was higher in those individuals who had an adverse clinical outcome after chemotherapy.

Effects of Eradication of HCV on Cardiovascular Risk and Preclinical Atherosclerosis in HIV/HCV-Coinfected Patients.

BACKGROUND: To assess the effects of eradication of hepatitis C virus (HCV) on cardiovascular risk (CVR) and preclinical atherosclerosis in HIV/HCV-coinfected patients. SETTING: Prospective cohort study. METHODS: We assessed serum lipids, 10-year Framingham CVR scores, pulse wave velocity, carotid intima-media thickness, and biomarkers of inflammation and endothelial dysfunction (BMKs) at baseline and 96 weeks (wk) after initiation of anti-HCV therapy (Rx) in HIV/HCV-coinfected patients. RESULTS: A total of 237 patients were included. Anti-HCV therapy comprised pegylated interferon and ribavirin plus 1 direct-acting antiviral in 55.2%, pegylated interferon and ribavirin in 33.8%, and all-oral direct-acting antiviral in 11.0%. A total of 147 (62.0%) patients achieved sustained viral response (SVR). Median increases in low-density lipoprotein cholesterol in patients with and without SVR were 14 mg/dL and 0 mg/dL (P = 0.024), respectively. Increases in CVR categories were found in 26.9% of patients with SVR (P = 0.005 vs. baseline) and 8.1% of patients without SVR (P = 0.433). This resulted in a significant interaction between SVR and CVR over time (P < 0.001). No significant effect of SVR was observed for pulse wave velocity (P = 0.446), carotid intima-media thickness (P = 0.320), and BMKs of inflammation and endothelial dysfunction. CONCLUSIONS: In coinfected patients, eradication of HCV had no effect on markers of preclinical atherosclerosis and BMKs of inflammation and endothelial dysfunction but was associated with a clinically relevant rise in serum low-density lipoprotein cholesterol. Evaluation of CVR should be an integral part of care after the cure of chronic hepatitis C in patients with HIV.

The Influence of Patient Experience with Healthcare on the Health-Related Quality of Life of People Living with HIV: An Observational Cross-Sectional Survey.

INTRODUCTION: Patient experience is central to the quality of healthcare delivery, showing positive associations with several outcome measures. The main objectives of this study are to analyze the influence of patient experience on the health-related quality of life in people living with HIV and the role played by treatment complexity and clinical care. METHODS: We conducted a cross-sectional survey with 467 patients with HIV. We used the Instrument for Evaluation of the Experience of Chronic Patients and the Health-related Quality of Life Questionnaire (EQ-5D-5L). We analyzed a predictive model through the partial least squares (PLS) method. RESULTS: The patient self-management scores showed the highest positive relationship with the patient's health-related quality of life (ß = 0.24, ß = 0.32, p < 0.0001). Patients' treatment complexity had a negative influence on health-related quality of life (ß = - 0.21, ß = - 0.28, p < 0.0001). The complexity of clinical care had negative effects on health-related quality of life, both directly (ß = - 0.37, ß = - 0.19, p < 0.0001) and through its negative influence on the productive interactions with healthcare professionals (ß = - 0.21, p < 0.0001) and patient self-management factors (ß = - 0.21, p < 0.0001). The effects of patient experience dimensions on their health-related quality of life were higher in people living with HIV > 50 years old (p < 0.05). CONCLUSIONS: Patient experience mainly influenced the health-related quality of life of older people living with HIV. The treatment and clinical care complexity played an important role in degrading the patients' experience and their quality of life. More integrated care would benefit the health-related quality of life of people living with HIV. FUNDING: This project was funded by Merck Sharp & Dohme, Spain.

The experience of inflammatory bowel disease patients with healthcare: A survey with the IEXPAC instrument.

To assess inflammatory bowel disease (IBD) patients' experience of chronic illness care and the relationship with demographic and healthcare-related characteristics.This cross-sectional survey used the Instrument to Evaluate the EXperience of PAtients with Chronic diseases (IEXPAC) questionnaire to identify parameters associated with a better healthcare experience for IBD patients. IEXPAC questionnaire responses are grouped into 3 factors - productive interactions, new relational model, and patient self-management, scoring from 0 (worst) to 10 (best experience). Scores were analyzed by bivariate comparisons and multiple linear regression models.Surveys were returned by 341 of 575 patients (59.3%, mean age 46.8 (12.9) years, 48.2% women). Mean (SD) IEXPAC score was 5.9 (2.0); scores were higher for the productive interactions (7.7) and patient self-management factors (6.7) and much lower for the new relational model factor (2.2). Follow-up by a nurse, being seen by the same physician, and being treated with a lower number of medicines were associated with higher (better) overall patient experience score, and higher productive interactions and self-management factor scores. A higher productive interactions score was also associated with patients receiving medication subcutaneously or intravenously. Higher new relational model scores were associated with follow-up by a nurse, affiliation to a patients' association, receiving help from others for healthcare, a lower number of medicines and a higher educational level.In patients with IBD, a better overall patient experience was associated with follow-up by a nurse, being seen by the same physician, and being treated with a lower number of medicines.

Effectiveness and safety of dual therapy with rilpivirine and boosted darunavir in treatment-experienced patients with advanced HIV infection: a preliminary 24 week analysis (RIDAR study).

BACKGROUND: The objective was to analyze the effectiveness and safety of dual therapy with rilpivirine plus boosted-darunavir (RPV + bDRV) in real-life patients. METHODS: Observational, retrospective, multi-center study in HIV+ patients who had received RPV + bDRV for 24 weeks to optimize/simplify their previous antiretroviral treatment. We determined the percentage of patients without virologic failure (2 consecutive viral loads > 50 copies/mL) at 24 weeks of treatment. RESULTS: The study included 161 patients from 15 hospitals with median age of 49 years; 29.3% had previous AIDS stage and median CD4+ lymphocyte nadir of 170 cells/uL. They had been diagnosed with HIV for a median of 17 years and had received 14 years of ART, with five previous treatment combinations, and 36.6% had a history of virological failure. The reasons for the switch were simplification/optimization (49.7%), toxicity/intolerance (17.4%), or inadequate effectiveness of previous ART (10.6%). Baseline VL of 50-1000 copies/mL was recorded in 25.5% of the patients. In the"intention-to-treat" analysis at 24 weeks, 87.6% of 161 patients continued the study treatment without virologic failure criteria. In the "on treatment" analysis (excluding patients who discontinued treatment with dual therapy for any reason other than virologic failure) the efficacy was 94.6% (141/149 patients). CONCLUSIONS: Dual therapy with RPV + DRVb proved to be effective and safe in patients with advanced HIV infection, long exposure to ART, low CD4 nadir, previous virologic failure, and/or history of ineffective ART.

Low performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. METHODS: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used. RESULTS: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (P < 0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (P = 0.038). CONCLUSION: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.

Healthcare Experience and their Relationship with Demographic, Disease and Healthcare-Related Variables: A Cross-Sectional Survey of Patients with Chronic Diseases Using the IEXPAC Scale.

BACKGROUND: Patient experience is acknowledged as a principal aspect of quality healthcare delivery, and it has implications with regard to outcomes. OBJECTIVES: Our objective was to evaluate the healthcare experience of patients with chronic diseases to identify patient-perceived healthcare gaps and to assess the influence of demographic and healthcare-related variables on patient experiences. METHODS: A cross-sectional survey was delivered to adult patients with chronic diseases: diabetes mellitus (DM), human immunodeficiency virus (HIV) infection, inflammatory bowel disease (IBD) or rheumatic diseases. Patient experiences were assessed with the Instrument for Evaluation of the Experience of Chronic Patients (IEXPAC) questionnaire, with possible scores ranging from 0 (worst) to 10 (best experience). RESULTS: Of the 2474 patients handed the survey, 1618 returned it (response rate 65.4%). Patients identified gaps in healthcare related mainly to access to reliable information and services, interaction with other patients and continuity of healthcare after hospital discharge. The mean ± standard deviation (SD) IEXPAC score was 6.0 ± 1.9 and was higher for patients with HIV (6.6 ± 1.7) than for those with rheumatic disease (5.5 ± 2.0), IBD (5.9 ± 2.0) or DM (5.9 ± 1.9) (p < 0.001). In multivariate models, better overall IEXPAC experience was associated with follow-up by the same physician, follow-up by a nurse, receiving healthcare support from others and treatment with subcutaneous or intravenous drugs. The multivariate model that confirmed patients with HIV or DM had better experience than did those with rheumatic diseases. CONCLUSIONS: Through IEXPAC, patients identified aspects for healthcare quality improvements and circumstances associated with better experience, which may permit greater redirection of healthcare toward patient-centered goals while facilitating improvements in social care and long-term healthcare quality.

Hepatocellular carcinoma after sustained virological response with interferon-free regimens in HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (P = 1.0). CONCLUSION: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.

Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant.

BACKGROUND: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. METHODS: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. RESULTS: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. CONCLUSIONS: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.

Efavirenz: What is known about the cellular mechanisms responsible for its adverse effects.

The HIV infection remains an important health problem worldwide. However, due to the efficacy of combined antiretroviral therapy (cART), it has ceased to be a mortal condition, becoming a chronic disease instead. Efavirenz, the most prescribed non-nucleoside analogue reverse transcriptase inhibitor (NNRTI), has been a key component of cART since its commercialization in 1998. Though still a drug of choice in many countries, its primacy has been challenged by the arrival of newer antiretroviral agents with better toxicity profiles and treatment adherence. The major side effects related to EFV have been widely described in clinical studies, however the mechanisms that participate in their pathogenesis remain largely ununderstood. This review provides an insight into the cellular and molecular mechanisms responsible for the development of the most significant undesired effects induced by efavirenz, both short- and long-term, revealed by in vitro and in vivo experimental pharmacological research. Growing evidence implicates the drug in energy metabolism, mitochondrial function, and other cellular processes involved in stress responses including oxidative stress, inflammation and autophagy.

Cardiovascular toxicity of abacavir: a clinical controversy in need of a pharmacological explanation.

: There is a long-lasting controversy surrounding an association between abacavir (ABC) and an increased risk of cardiovascular disease in HIV-positive patients. Although differing in their specifics, a number of published cohort studies and clinical trials support such an association, usually relating it to recent exposure to the drug, independently of traditional predisposing factors. However, other clinical trials have failed to reveal such a relation and have pointed to methodological differences to explain discrepancies. Significantly, the controversy has been fueled by the lack of a credible mechanism of action to justify the putative detrimental actions of ABC. There is a myriad of contradictory clinical indicators which are not clearly compatible with known profiles of either vascular physiopathology or pharmacological interference. However, basic research has recently hinted at altered homeostatic mechanisms, though this requires clinical validation. In particular, recurrent evidence - both clinical and experimental - relates ABC with vascular inflammation, a leading contributor to the atherosclerotic plaque and thrombosis. ABC's chemical structure is very close to that of endogenous purines (ATP, ADP and AMP), major paracrine signaling molecules capable of triggering prothrombotic and proinflammatory vascular programs. Other proposed mechanisms are a competitive inhibition of guanylyl cyclase in platelets and a subsequent decrease in cyclic guanosine monophosphate (cGMP). The present review aims to shed light on this complex subject by summarizing and critically evaluating all the available clinical data regarding a relationship between ABC and cardiovascular disease, and to put forward potential pharmacological explanations compatible with both the clinical scenario and experimental findings.