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

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date.</p> <p>Methods</p> <p>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 enrolment, 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 enrolment and yearly thereafter.</p> <p>Results</p> <p>A total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrolment 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.</p> <p>Conclusion</p> <p>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.</p

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

International audienceOBJECTIVES: 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

Hepatology

INTRODUCTION: It is widely accepted that HIV infection is a risk factor for increased severity of HCV liver disease. However, owing to better efficacy and safety of cART, and increased access to HCV therapy, whether this condition remains true is still unknown. METHODS: 1,253 HCV mono-infected patients and 175 HIV/HCV co-infected cirrhotic patients, included in two prospective French national cohorts (ANRS CO12 CirVir and CO13 HEPAVIH) were studied. Cirrhosis was compensated (Child-Pugh A), without prior history of complication, and assessed on liver biopsy. Incidences of liver decompensation, 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. RESULTS: 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. 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 (SHR=1.88; 95% CI: 1.15-3.06, p = 0.011). Factors associated with liver decompensation and HCC were age, absence of SVR 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 cirrhotic patients, HIV co-infection was no longer associated with higher risks of HCC and hepatic decompensation. Increased mortality however persisted, due to extra-hepatic conditions. This article is protected by copyright. All rights reserved

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

International audiencePostnatal 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

Number of women and children by peri-partum short-course (sc) antiretroviral regimen and infant-feeding modality for prevention of Mother-To-Child transmission (PMTCT) of HIV.

<p>ANRS 1201/1202 Ditrame-Plus and ANRS 049a DITRAME cohorts, Abidjan, Côte d'Ivoire.</p><p>ZDV = short-course zidovudine; sdNVP = single-dose nevirapine during labour; 3TC = lamivudine.</p>*<p>Eight formula-fed children were excluded.</p>**<p>Two children were not classified for infant feeding modality.</p

Determinants of 18-month HIV-1 infection or death (Cox proportional hazard model; reference: ZDV long-term breastfed).

<p>ANRS 1201/1202 Ditrame-Plus and ANRS 049a DITRAME cohorts, Abidjan, Côte d'Ivoire.</p><p>*Variables with p<0.25 in the comparison of the three treatment groups (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001645#pone-0001645-t002" target="_blank">table 2</a>). ^§Estimated cumulative transmission risk (CTR) of HIV-1 infection at 18-month using Kaplan-Meier estimates. ^§§Log-rank test; CI: confidence interval; ^#univariate = unadjusted Cox proportional hazards model; HR: hazard ratio; HRa: adjusted Hazard Ratio; 3TC = lamivudine; sdNVP = single-dose nevirapine during labour; ZDV  = zidovudine. ART = highly active antiretroviral therapy if WHO clinical stage 4 or WHO clinical stage 3 and CD4<350 /mm³ or WHO clinical stage 1/2 and CD4<200/mm³. #in the adjusted analysis, this variable took into account both the treatment duration and the antiretroviral regimen used.</p

18-Month mortality and perinatal exposure to zidovudine in West Africa.

OBJECTIVES: To study mortality in African children born to HIV-1-infected mothers exposed peripartum to zidovudine. METHODS: A randomized placebo-controlled trial in Abidjan and Bobo-Dioulasso. Pregnant women received either 300 mg zidovudine twice daily from 36-38 weeks' gestation, 600 mg during labour, and 300 mg twice daily for 7 days post-partum or a matching placebo. Determinants of mortality were studied up to 18 months, overall and among the infected children: treatment, centre, timing of infection, mother and child HIV disease. RESULTS: There were 75 infant deaths among 407 live births. The risk of death at 18 months was 176/1000 in the zidovudine arm and 221 for placebo. Relative hazard (RH, zidovudine versus placebo) was 0.47 [95% confidence interval (CI) 0.2-1.0] up to 230 days of life. Maternal CD4 lymphocyte count < 200/mm3 (RH 2.92; CI 1.4-6.1) and child HIV-1 infection (RH 12.6; CI 6.6-24.3) increased mortality of all children born to HIV-1-infected mothers. There were 101 children infected (40 in the zidovudine group), and 51 died. Their 18 month probability of death was 590/1000 in the zidovudine group and 510 in the placebo group. Among infected children, maternal zidovudine reduced the risk of death on or before day 230 (RH 0.18; CI 0.1-0.5). Maternal CD4 lymphocyte count < 200/mm3 (RH 3.25; CI 1.3-8.4), maternal death (RH 9.65; CI 1.7-56.0), diagnosis of paediatric infection on or before day 12 (RH 18.1; CI 4.8-69.0) and between days 13 and 45 (RH 7.63; CI 2.0-29.5), clinical paediatric AIDS (RH 5.37; CI 2.3-12.7) were risk factors for death in HIV-1-infected children. CONCLUSION: Mother-to-child transmission reduction by zidovudine is safe and beneficial to African children. The mortality of HIV-1-infected children is high. Peripartum maternal zidovudine exerts a protective effect for at least 8 months