Human Immunodeficiency Virus/Hepatitis C Virus (HCV) Co-infected Patients With Cirrhosis Are No Longer at Higher Risk for Hepatocellular Carcinoma or End-Stage Liver Disease as Compared to HCV Mono-infected Patients.

It is widely accepted that human immunodeficiency virus (HIV) infection is a risk factor for increased severity of hepatitis C virus (HCV) liver disease. However, owing to better efficacy and safety of combination antiretroviral therapy (cART), and increased access to HCV therapy, whether this condition remains true is still unknown. Overall, 1,253 HCV mono-infected patients and 175 HIV/HCV co-infected patients with cirrhosis, included in two prospective French national cohorts (ANRS CO12 CirVir and CO13 HEPAVIH), were studied. Cirrhosis was compensated (Child-Pugh A), without past history of complication, and assessed on liver biopsy. Incidences of liver decompensation (LD), hepatocellular carcinoma (HCC), and death according to HIV status were calculated by a Fine-Gray model adjusted for age. Propensity score matching was also performed to minimize confounding by baseline characteristics. At baseline, HIV/HCV patients were younger (47.5 vs. 56.0 years; P < 0.001), more frequently males (77.1% vs. 62.3%; P < 0.001), and had at baseline and at end of follow-up similar rates of HCV eradication than HCV mono-infected patients. A total of 80.4% of HIV/HCV patients had an undetectable HIV viral load. After adjustment for age, 5-year cumulative incidences of HCC and decompensation were similar in HIV/HCV and HCV patients (8.5% vs. 13.2%, P = 0.12 and 12.8% vs. 15.6%, P = 0.40, respectively). Overall mortality adjusted for age was higher in HIV/HCV co-infected patients (subhazard ratio [SHR] = 1.88; 95% confidence interval [CI], 1.15-3.06; P = 0.011). Factors associated with LD and HCC were age, absence of sustained virological response, and severity of cirrhosis, but not HIV status. Using a propensity score matching 95 patients of each group according to baseline features, similar results were observed. Conclusion: In HCV-infected patients with cirrhosis, HIV co-infection was no longer associated with higher risks of HCC and hepatic decompensation. Increased mortality, however, persisted, attributed to extrahepatic conditions.

The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): early findings, 2006-2010.

BACKGROUND: In France, it is estimated that 24% of HIV-infected patients are also infected with HCV. Longitudinal studies addressing clinical and public health questions related to HIV-HCV co-infection (HIV-HCV clinical progression and its determinants including genetic dimension, patients' experience with these two diseases and their treatments) are limited. The ANRS CO 13 HEPAVIH cohort was set up to explore these critical questions.To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date. METHODS: Inclusion criteria in the cohort were: age > 18 years, HIV-1 infection, chronic hepatitis C virus (HCV) infection or sustained response to HCV treatment. A standardized medical questionnaire collecting socio-demographic, clinical, biological, therapeutic, histological, ultrasound and endoscopic data is administered at enrollment, then every six months for cirrhotic patients or yearly for non-cirrhotic patients. Also, a self-administered questionnaire documenting socio-behavioral data and adherence to HIV and/or HCV treatments is administered at enrollment and yearly thereafter. RESULTS: A total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrollment was 45 years and 70.2% were male. The median CD4 cell count was 442 (IQR: 304-633) cells/µl and HIV RNA plasma viral load was undetectable in 68.8%. Most participants (71.6%) were on HAART. Among the 1,048 HIV-HCV chronically co-infected patients, HCV genotype 1 was predominant (56%) and cirrhosis was present in 25%. As of January, 2010, after a median follow-up of 16.7 months (IQR: 11.3-25.3), 13 new cases of decompensated cirrhosis, nine hepatocellular carcinomas and 20 HCV-related deaths were reported, resulting in a cumulative HCV-related severe event rate of 1.9/100 person-years (95% CI: 1.3-2.5). The rate of HCV-related severe events was higher in cirrhotic patients and those with a low CD4 cells count, but did not differ according to sex, age, alcohol consumption, CDC clinical stage or HCV status. CONCLUSION: The ANRS CO 13 HEPAVIH is a nation-wide cohort using a large network of HIV treatment, infectious diseases and internal medicine clinics in France, and thus is highly representative of the French population living with these two viruses and in care.

Realist evaluation of a theory-based life skills programme aiming to prevent addictive behaviours in adolescents: the ERIEAS study protocol.

INTRODUCTION: Adolescence is a sensitive life stage during which tobacco, alcohol and cannabis are used as ways to learn and adopt roles. There is a great deal of interest in substance use (SU) prevention programmes for young people that work to change representations of these products and help with mobilisation of life skills. Unfortunately, few existing programmes are evidence-based.In France, a programme called Expériences Animées (EA, Animated Experiences) has been developed, inspired by life skills development programmes that have been proven to be successful. The EA programme uses animated short movies and talks with high school and secondary school pupils about the use of psychoactive substances and addictions. By allowing life skills mobilisation and modifying representations and beliefs about SU, it is aimed at delaying initiation of use of psychoactive substances, preventing adolescents from becoming regular consumers, reducing the risks and harms related to the use of these substances and opening the way for adapted support measures.We are interested in understanding how, under what circumstances, through which mechanisms and among which adolescents the EA programme works. Therefore, we have developed the ERIEAS study ('Evaluation Réaliste de l'Intervention Expériences Animées en milieu Scolaire'; Realist Evaluation of the EA Intervention in Schools). METHODS AND ANALYSIS: EA will be conducted in 10 schools. A multi-case approach will be adopted with the aim of developing and adjusting an intervention theory. The study comes under the theory-driven evaluation framework. The investigation methodology will include four stages: (i) elaboration of a middle-range theory; (ii) data collection for validating/adjusting the theory; (iii) data analysis; and (iv) refinement and adjustment of the middle-range theory and definition of the programme's key functions. ETHICS AND DISSEMINATION: The study will provide evidence-based results to health authorities to help in the rollout of health promotion strategies in schools. It will provide knowledge about the strategic configurations most suitable for leading to life skills mobilisation and change young people's representations about SU. The project will be carried out with full respect of current relevant legislation (eg, the Charter of Fundamental Rights of the European Union) and international conventions (eg, Helsinki Declaration). It follows the relevant French legislation of the research category on interventional research protocol involving the human person. The protocol was approved by the Comité et Protection des Personnes (CPP), that is, Committee for the Protection of Persons CPP SUD-EST VI n°: AU 1525 and was reported to the Agence Française de Sécurité Sanitaire des Produits de Santé (ANSM) that is, the French National Agency for the Safety of Health Products. It is in conformity with reference methodology MR003 of Bordeaux University Hospital (CNIL n° 2 026 779 v0).Trial registration detailsThis research has been registered on ClinicalTrials.gov (No. NCT04110626).The research project is registered in the European database ID-RCB (No. 2019-A01003-54).

Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission.

OBJECTIVES: In Africa, single-dose nevirapine (NVPsd), short regimens of zidovudine (ZDV) or ZDV + lamivudine (3TC) are recommended to prevent peripartum mother-to-child HIV transmission (PMTCT). We evaluated the 6-week field efficacy of two more PMTCT drug combinations. DESIGN: An open-label intervention cohort in Abidjan. METHODS: In 2001-2002, consenting women started oral ZDV 300 mg twice daily (bid) at > or =36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd orally at beginning of labour. In 2002-2003, the antepartum regimen at > or =32 weeks comprised ZDV as previously + 3TC 150 mg bid; the labour dose comprised ZDV + NVPsd as previously + 300 mg 3TC orally. Neonates received ZDV syrup (2 mg/kg per 6 h) for 7 days + NVPsd syrup (2 mg/kg) on day 2 in both periods. Each woman was assisted to either use breast milk substitutes or breastfeed exclusively. Paediatric HIV infection was diagnosed by plasma HIV RNA viral load at 4 weeks, confirmed at 6 weeks. The reference group was a cohort receiving a short regimen of ZDV > or = 36-38 weeks in 1995-2000 in the same population. RESULTS: A total of 1144 HIV-infected pregnant women were included: 351 with ZDV, 420 with ZDV + NVPsd and 373 with ZDV + 3TC + NVPsd; 1010 livebirths were eligible for analysis; 79 children were HIV-infected peripartum. Six-week transmission probability was 6.5% [95% confidence interval (CI), 3.9-9.1%) with ZDV + NVPsd, a 72% reduction compared with ZDV alone (95% CI, 52-88%; P = 0.0002 adjusted on maternal CD4, clinical stage and breastfeeding). It was 4.7% (95% CI, 2.4-7.0%) with ZDV + 3TC + NVPsd (P = 0.34 compared with ZDV + NVPsd). CONCLUSIONS: A short-course of ZDV + NVPsd prevents most peripartum HIV transmission in Africa. This regimen could be added to international guidelines.

Hepatitis C virus RNA quantitation in a nationwide French cohort of patients co-infected with HIV and HCV: should the same test be applied to all samples?

In the ANRS CO13 HEPAVIH Cohort, HCV RNA measurement was performed with one of the two available real-time PCR assays [Roche Cobas AmpliPrep-Cobas TaqMan HCV (CAP-CTM) and the Abbott Real-Time HCV (ART)], according to the assay used in each center. To comply with the recommendations for using the same assay in multicenter clinical trials, all the 204 samples analyzed with ART were retested retrospectively by CAP-CTM. The aim of this study was to assess the usefulness of this strategy in real-life situations. A significant and positive correlation was observed between HCV RNA levels measured in the same samples with ART and CAP-CTM with all the genotypes tested. However, in 33 of the 204 (16%) clinical samples, the individual difference between HCV RNA levels measured by both assays was above ±0.5 log(10)IU/ml. Such viral load variations above 0.5 log(10) should be considered as significant. HCV RNA levels estimated by CAP-CTM for genotype 4 were significantly lower than those for genotypes 1, 2, and 3 (P<0.0001). This study shows that using the same assay in multicenter trials and cohorts is still relevant due to inter-assay differences observed in HCV plasma load measurements.

18-month effectiveness of short-course antiretroviral regimens combined with alternatives to breastfeeding to prevent HIV mother-to-child transmission.

OBJECTIVE: We assessed the 18-month effectiveness of short-course (sc) antiretroviral peripartum regimens combined with alternatives to prolonged breastfeeding to prevent mother-to-child transmission (MTCT) of HIV-1 in Abidjan, Côte d'Ivoire. METHODOLOGY: HIV-1 infected pregnant women received from >/=32-36 weeks of gestation scZidovudine (ZDV)+/-Lamivudine (3TC)+single-dose Nevirapine (sdNVP) at delivery within the ANRS 1201/1202 DITRAME-Plus cohort (2001-2003). Neonates received a sdNVP+7-day ZDV prophylaxis. Two infant-feeding interventions were systematically offered free of charge: formula-feeding or exclusive shortened breastfeeding with early cessation from four months. The reference group was the ANRS 049a DITRAME cohort (1994-2000) exposed to scZDV from 36 weeks, then to prolonged breastfeeding. Pediatric HIV infection was defined by a positive plasma HIV-1 RNA at any age, or if aged >/=18 months, a positive HIV-1 serology. Turnbull estimates of cumulative transmission risks (CTR) and effectiveness (HIV-free survival) were compared by exposure group using a Cox model. FINDINGS: Among 926 live-born children enrolled, 107 (11.6%) were HIV-infected at 18 months. CTRs were 22.3% (95% confidence interval[CI]:16-30%) in the 238 ZDV long-term breastfed reference group, 15.9% (CI:10-27%) in the 169 ZDV+sdNVP shortened breastfed group; 9.4% (CI:6-14%) in the 195 ZDV+sdNVP formula-fed group; 6.8% (CI:4-11%) in the 198 ZDV+3TC+sdNVP shortened breastfed group, and 5.6% (CI:2-10%) in the 126 ZDV+3TC+sdNVP formula-fed group. Each combination had a significantly higher effectiveness than the ZDV long-term breastfed group except for ZDV+sdNVP shortened breastfed children, ranging from 51% (CI:20-70%) for ZDV+sdNVP formula fed children to 63% (CI:40-80%) for ZDV+3TC+NVPsd shortened breastfed children, after adjustment for maternal eligibility for antiretroviral therapy (ART), home delivery and low birth-weight. Substantial MTCT risk reductions are reachable in Africa, even in short-term breastfed children. The two sc antiretroviral combinations associated to any of the two infant feeding interventions, formula-feeding and shortened breastfeeding, reduce significantly MTCT with long-term benefit until age 18 months and without increasing mortality.

Estimating the efficacy of interventions to prevent mother-to-child transmission of human immunodeficiency virus in breastfeeding populations: comparing statistical methods.

Postnatal transmission of human immunodeficiency virus infection through breastfeeding complicates evaluating the efficacy of interventions aimed to reduce mother-to-child transmission risk. Results from trials in Africa evaluating either peripartum antiretroviral therapy or refraining from breastfeeding show an estimated long-term efficacy at 15-24 months of age between 25 and 50 percent. Differences in statistical methods, duration of follow-up, and age at weaning hinder direct comparison between trials. The authors recently outlined theoretically preferred statistical methods for evaluating interventions aimed to reduce risk of mother-to-child transmission of human immunodeficiency virus. When multiple test results and/or supplementary information is available, the more sophisticated methods account for the fact that exact age at infection is unknown, that risk for infection ends at weaning, or that censoring due to death may be informative. The authors apply these methods to four scenarios, using data from four randomized trials carried out in Africa between 1995 and 2000. The authors' findings suggest that, to estimate the cumulative proportion infected at age 6 weeks, a standard Kaplan-Meier approach is likely to give valid results. For estimation of this proportion at age 18 months, more sophisticated methods, such as the extension of the Kaplan-Meier procedure to interval-censored data and competing risks, would be preferred.