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Objectives: We report the association between pre‐antiretroviral therapy (pre‐ART) soluble vascular cell adhesion molecule‐1 (sVCAM‐1) levels and long‐term mortality in HIV‐infected West African adults participating in a trial of early ART in West Africa (Temprano ANRS 12136 trial). Methods: The ART‐naïve HIV‐infected adults were randomly assigned to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the trial follow‐up were invited to participate in a post‐trial phase (PTP). The PTP end‐point was all‐cause death. We used multivariable Cox proportional models to analyse the association between baseline sVCAM‐1 and all‐cause death, adjusting for ART strategy, sex, CD4 count, plasma HIV‐1 RNA and peripheral blood mononuclear cell HIV‐1 DNA levels. Results: In all, 954 adults (77% women, median CD4 count of 387 cells/μL) were randomly assigned to start ART immediately (n = 477) or to defer initiation of ART (n = 477). They were followed for a median of 5.8 years [interquartile range (IQR): 5.2–6.3]. In multivariable analysis, the risk of death was significantly associated with baseline sVCAM‐1 [≥1458 vs. < 1458 ng/mL; adjusted hazard ratio = 2.86, 95% confidence interval (CI): 1.60–5.11]. The 6‐year probability of death rates were 14.4% (95%CI: 9.1–22.6) and 9.4% (5.4–16.1) in patients with baseline sVCAM‐1 ≥ 1458 ng/mL randomized to deferred and immediate ART, respectively, and 3.8% (2.2–6.5) and 3.5% (1.9–6.3) in patients with baseline sVCAM‐1 < 1458 ng/mL randomized to deferred and immediate ART. The median difference between pre‐ART and 12‐month sVCAM‐1 levels in patients randomized to immediate ART was −252 (IQR: −587 to −61). Conclusions: Pre‐ART sVCAM‐1 levels were significantly associated with mortality, independently of whether ART was started immediately or deferred, but they significantly decreased after 12 months of ART. [ABSTRACT FROM AUTHOR]

Background: In Sub‐Saharan Africa, chronic hepatitis C (CHC) is a major public health issue. We estimated the long‐term clinical benefits of treating CHC with sofosbuvir‐based regimens in Cameroon, Côte d'Ivoire and Senegal using Markov model combining data from the literature with estimates of direct‐acting antiviral (DAAs) effectiveness in West and Central Africa. Methods: Disease progression was simulated with and without treatment in fictive cohorts of patients "diagnosed" with CHC in Cameroon (n = 3224), Côte d'Ivoire (n = 9748) and Senegal (n = 6358). Lifetime treatment benefits were assessed using (a) life‐years saved (LYS); (b) life‐years (LY) avoided in compensated cirrhosis (CC), decompensated cirrhosis (DC) and hepatocellular carcinoma; and (c) comparison of the proportions of patients at each disease stage with and without treatment. Probabilistic and determinist sensitivity analyses were performed to address uncertainty. Results: Sofosbuvir‐based treatment would save [mean, 95% confidence intervals] 3.3 (2.5; 5.7) LY per patient in Cameroon, 2.7 (2.1; 4.8) in Côte d'Ivoire and 3.6 (2.8; 6.3) in Senegal. With treatment, approximately 6% (1%) of the patients still alive in each of the study countries would be in the CC (DC) health state 11 (15) years after CHC diagnosis, vs 15% (5%) without treatment. Scenario analysis showed earlier diagnosis and treatment initiation would dramatically improve LYS and morbidity. Conclusion: Sofosbuvir‐based treatment could significantly reduce CHC‐related mortality and help control CHC‐related liver disease progression in West and Central Africa. However, the goal of disease elimination necessitates a substantial decrease in DAAs prices, greater political commitment and increases in both national and external health expenditures. [ABSTRACT FROM AUTHOR]

Background. In human immunodeficiency virus (HIV)-infected patients, hepatitis B virus (HBV) coinfection increases the risk of disease progression. Tenofovir plus emtricitabine/lamivudine (TDF/XTC)-based antiretroviral therapy (ART), which suppresses HIV and HBV replication, has the potential for decreasing this risk. Here, we analyze the association between HBV replication, early ART, and mortality in West African adults. Methods. The Temprano randomized controlled trial assessed the benefits of immediately initiating vs deferring ART in HIVinfected adults with high CD4 counts. After trial completion, participants continued follow-up in a posttrial phase. We analyzed the association between HBV status, immediate ART, and mortality over the entire trial and posttrial follow-up using multivariable Cox proportional hazards regression. Results. A total of 2052 HIV-infected adults (median baseline CD4 count, 464 cells/µL) were followed for 9394 person-years. At baseline, 1862 (91%) were HIV monoinfected and 190 (9%) HIV/HBV coinfected. Of the latter, 135 (71%) had plasma HBV DNA <2000 IU/mL and 55 (29%) HBV DNA ≥2000 IU/mL. The 60-month probability of death was 11.8% (95% confidence interval [CI], 5.4%-24.5%) in coinfected patients with HBV DNA ≥2000 IU/mL; 4.4% (95% CI, 1.9%-10.4%) in coinfected patients with HBV DNA <2000 IU/mL; and 4.2% (95% CI, 3.3%-5.4%) in HIV-monoinfected patients. Adjusting for ART strategy (immediate vs deferred), the hazard ratio of death was 2.74 (95% CI, 1.26-5.97) in coinfected patients with HBV DNA ≥2000 IU/mL and 0.90 (95% CI, .36-2.24) in coinfected patients with HBV DNA <2000 IU/mL compared to HIV-monoinfected patients. There was no interaction between ART strategy and HBV status for mortality. Conclusions. African HIV/HBV-coinfected adults with high HBV replication remain at heightened risk of mortality in the early ART era. Further studies are needed to assess interventions combined with early ART to decrease mortality in this population. [ABSTRACT FROM AUTHOR]

Objective: To assess the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) test for active tuberculosis (TB) in HIV adults, and its variation over time in patients on antiretroviral therapy (ART) and/or isoniazide preventive therapy (IPT). Methods: Transversal study and cohort nested in the Temprano ANRS 12136 randomized controlled trial assessing benefits of initiating ART earlier than currently recommended by World Health Organization, with or without a 6-month IPT. Performance of QFT-GIT for detecting active TB at baseline in the first 50% participants, and 12-month incidence of conversion/reversion in the first 25% participants were assessed. QFT-GIT threshold for positivity was 0.35 IU/ml. Results: Among the 975 first participants (median baseline CD4 count 383/mm3, positive QFT-GIT test 35%), 2.7% had active TB at baseline. QFT-GIT sensitivity, specificity, positive and negative predictive value for active TB were 88.0%, 66.6%, 6.5% and 99.5%. For the 444 patients with a second test at 12 months, rates for conversion and reversion were 9.3% and 14%. Reversion was more frequent in patients without ART and younger patients. IPT and early ART were not associated with reversion/conversion. Conclusion: A negative QFT-GIT could rule out active TB in HIV-infected adults not severely immunosuppressed, thus avoiding repeated TB testing and accelerating diagnosis and care for other diseases. Trial Registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]