Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus.

BACKGROUND: An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. METHODS: HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. RESULTS: At baseline, median age of the study population (N = 1213) was 45.4 (interquartile range [IQR] 42.1-49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9-7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19-9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78-6.00) for coronary and/or cerebral events, and 3.17 (2.05-4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01-1.12), prior CVD (HR 8.48; 95% CI, 3.14-22.91), high total cholesterol (HR 1.43; 95% CI, 1.11-1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08-0.63), statin use (HR 3.31; 95% CI, 1.31-8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35-7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18-0.96) was associated with coronary and/or cerebral events. CONCLUSIONS: HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk.

Liver stiffness and fibrosis-4 alone better predict liver events compared with aspartate aminotransferase to platelet ratio index in a cohort of human immunodeficiency virus and hepatitis C virus co-infected patients from ANRS CO13 HEPAVIH cohort.

OBJECTIVES: HIV/hepatitis C virus (HCV) co-infection leads to major complications, and noninvasive markers developed to stage liver fibrosis could be used as prognostic markers. We aimed to compare the performances of liver stiffness (LS), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) to predict liver-related events in HIV/HCV co-infected patients. PATIENTS AND METHODS: HIV/HCV co-infected patients from the ANRS CO13 HEPAVIH cohort were included if they had LS, FIB-4, and APRI measurements done in a window of 3 months. Primary outcome was the time between inclusion and occurrence of a liver-related event. Univariable and multivariable Fine and Gray models were performed. Predictive performances were compared by the area under the receiver operating characteristic (AUROC) differences after correction of optimistic by bootstrap samples. Best cutoffs to predict liver-related events were estimated by sensitivity and specificity maximization. RESULTS: A total of 998 patients were included. Overall, 70.7% were men. Their median age was 46.8 years. According to LS value, 204 (20.4%) patients had cirrhosis. Overall, 39 patients experienced at least one liver-related event. In univariable analysis, LS AUROC curve was significantly superior to FIB-4 and APRI AUROC curves, being 87.9, 78.2, and 75.0%, respectively. After adjustment on age, CD4 levels, and insulin resistance, no differences were observed. The best cutoffs to identify patients at low or high risk of liver-related events were below 8.5, 1.00, and 0.35 and above 16.5, 4.00, and 1.75 for LS, FIB-4, and APRI, respectively. CONCLUSION: To predict HCV-related events, APRI had lower performance than LS and FIB-4. FIB-4 is as good as LS to predict HCV-related events, suggesting that it can be used for the management of HIV/HCV co-infected patients and replace LS.

Increased liver stiffness is associated with mortality in HIV/HCV coinfected subjects: The French nationwide ANRS CO13 HEPAVIH cohort study.

BACKGROUND: The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. METHODS: HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. RESULTS: 1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4-49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2-6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders. CONCLUSION: Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.

Factors associated with non-AIDS-defining cancers and non HCV-liver related cancers in HIV/HCV-coinfected patients- ANRS-CO13 HEPAVIH cohort.

Compared to the general population, HIV-infected patients are at higher risk of developing non-AIDS-defining cancers. Chronic HCV infection has also been associated with a higher risk than that of the general population of developing cancers other than hepatocarcinoma. Evaluation of the impact of HCV-related factors on non-AIDS-defining and non HCV-liver (NANL) related cancers among HIV/HCV co-infected patients are scarce. The aim of this study was to identify the impact of HIV/HCV clinical characteristics on NANL related cancers in a large cohort of HIV/HCV-coinfected patients followed from 2005 to 2017. Cox proportional hazards models with delayed entry were used to estimate factors associated with NANL related cancer. Among 1391 patients followed for a median of 5 years, 60 patients developed NANL related cancers, yielding an incidence rate of 8.9 per 1000 person-years (95% CI, [6.6-11.1]). By final multivariable analysis, after adjustment for sex, tobacco or alcohol consumption, baseline CD4 cell count and HCV sustained viral response (SVR), age and a longer duration since HIV diagnosis were independently associated with a higher risk of NANL related cancer (aHR for each additional year 1.10, 95% CI 1.06-1.14, p<0.0001 and 1.06, 95% CI 1.01-1.11, p = 0.02, respectively). Duration of HCV infection, cirrhosis, HCV viral load, genotype and SVR were not associated with the occurrence of NANL related cancer. Among HIV/HCV-coinfected patients, age and the duration of HIV infection were the only characteristics found to be associated with the occurrence of NANL related cancer. In contrast, no association was observed with any HCV-related variables.

Antiretroviral therapy and sustained virological response to HCV therapy are associated with slower liver fibrosis progression in HIV-HCV-coinfected patients: study from the ANRS CO 13 HEPAVIH cohort.

BACKGROUND: The aim of this study was to describe changes in repeated liver stiffness (LS) measurements and to assess the determinants of increase in LS in HIV-HCV-coinfected patients. METHODS: HIV-HCV-coinfected adults enrolled in the ANRS CO 13 HEPAVIH cohort, for whom two results of LS, evaluated over ≥24 months, were available. Patients with unreliable LS results were not included. LS was measured at baseline and every year thereafter. Determinants of LS increase were assessed using linear (primary outcome: last LS minus first LS value) and logistic (secondary outcome: ≥30% increase in the initial LS value) regression analyses. RESULTS: A total of 313 patients (mean age 45 years, 67.4% male) were included. Overall, 93.9% were receiving antiretroviral treatment (ART). The mean baseline CD4(+) T-cell count was 471 cells/mm(3) and 72.2% of patients had undetectable plasma HIV RNA. The mean interval between the first and last LS measurements was 33.5 months. No significant difference was found between baseline and follow-up mean LS values (P=0.39). However, a decrease of ≥30% in LS was observed in 48 (15.3%) patients and an increase of ≥30% in 64 (20.5%) patients. In multivariate linear and logistic analyses, excessive alcohol intake (ß coefficient 6.8; P=0.0006) and high HCV viral load (OR 1.7, 95% CI 1.1, 2.5; P=0.01) were independently associated with an increase in LS, whereas time on ART>114.5 months (OR 0.5, 95% CI 0.3, 0.9; P=0.03) and achievement of sustained virological response (OR 0.1, 95% CI 0.01, 0.9; P=0.04) were independently associated with no increase in LS. CONCLUSIONS: Our findings show that long-term ART and achieving sustained virological response in HIV-HCV-coinfected patients are both significantly associated with lack of increase in LS over a 33-month period.

Buprenorphine versus methadone in pregnant opioid-dependent women: a prospective multicenter study.

PATIENTS AND METHODS: In order to investigate the effects of exposure to buprenorphine compared with methadone during pregnancy, a prospective multicenter study was conducted in collaboration with maternity hospitals, maintenance therapy centers, and general practitioners involved in addiction care. Ninety pregnant women exposed to buprenorphine and 45 to metadone were selected for the study. RESULTS: During pregnancy, some women were exposed to illicit agents: cannabis (42% in the buprenorphine group vs. 58% in the methadone-treated group), heroin (17% vs. 44%), or cocaine (3% vs. 11%). Pregnancies ended in 85 vs. 40 live births, one vs. two stillbirths, two vs. one spontaneous abortion, two vs. one voluntary termination, and one vs. one medical termination in the buprenorphine and the methadone groups, respectively. Newborns had a birth weight of 2,892 ± 506 g (buprenorphine) vs. 2,731 ± 634 g (methadone) and a body length of 47.6 ± 2.5 cm vs. 47.1 ± 3 cm. 18.8% vs. 10% of newborns were delivered before 37 weeks of amenorrhea. Neonatal withdrawal syndrome occurred more frequently in the methadone group (62.5% vs. 41.2, p = 0.03). After adjustment for heroin exposure in late pregnancy, rates of neonatal withdrawal were no longer different between the methadone and buprenorphine groups. Twenty-one babies (84%) in the methadone group and 20 (57%) in the buprenorphine group (p = 0.03) required opiate treatment. CONCLUSIONS: We did not observe more frequent malformations or cases of withdrawal syndrome in the buprenorphine group than in the methadone-treated group. Buprenorphine appears to be as safe as the currently approved substitute methadone considered to date as the reference treatment for pregnant opioid-dependent women.

[Analysis of antiretroviral drugs-induced adverse effects]. / Analyse des effets indésirables des médicaments du VIH.

In 1999, The Regional Center of Pharmacogilance and the Department of Infectious Disease of the Toulouse University Hospital set up a system to improve the data collection about antiretroviral-induced adverse reactionss (ADRs). From November 1999 to April 2003, a resident of pharmacovigilance collected ADRs reported with antiretroviral drugs during 2 weekly medical consultations. A total of 613 ADRs corresponding to 428 patients were reported, classified as "non serious" in 88.6% of cases and required the withdrawal of suspected drugs in 57% of cases. Our data show an improvement of antiretroviral drug-induced ADRs reporting.

[Not Available]. / Analyse des effets indésirables des médicaments du VIH.

Analysis of Antiretroviral Drugs-Induced Adverse Elfects. In 1999, The Regional Center of Pharmacogilance and the Department of Infectious Disease of the Toulouse University Hospital set up a system to improve the data collection about antiretroviral-induced adverse reactionss (ADRs). From November 1999 to April 2003, a resident of pharmacovigilance collected ADRs reported with antiretroviral drugs during 2 weekly medical consultations. A total of 613 ADRs corresponding to 428 patients were reported, classified as "non serious" in 88.6% of cases and required the withdrawal of suspected drugs in 57% of cases. Our data show an improvement of antiretroviral drug-induced ADRs reporting.