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Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. Among its 8 genotypes (GT), GT3 has a relatively lower sustained virological response to highly effective direct‐acting antiviral agents (DAA). Sofosbuvir (SOF), an anti‐NS5B polymerase inhibitor, is a core component of many anti‐HCV DAA cocktail regimens, and its resistant mutations are rare in clinics because these mutations usually severely impair the NS5B polymerase activity, including a mutation S282T in NS5B, the most frequently reported SOF‐resistant mutation. In this study, we selected SOF‐resistant variants of a previously developed GT3 subgenomic replicon (PR87A7). Two mutations were identified in the viral genome of SOF‐resistant PR87A7 variants, Q606R in nontargeted NS3 and S282T in targeted N5SB. We demonstrated that Q606R could rescue the replication defect of S282T in PR87A7, and the resulting double mutant confers the SOF resistance. Finally, we showed that NS3‐606R could not compensate for the replication defect of S282T in other GTs. In conclusion, we identified a novel GT3‐specific combination of two mutations that confers SOF resistance. Our result calls for attention to potential mutations that may arise in nontargeted viral proteins during the SOF‐based DAA treatment of chronic HCV. [ABSTRACT FROM AUTHOR]

Background This meta-analysis was conducted to estimate the global burden of hepatitis B virus (HBV) infection in people living with human immunodeficiency virus (PLWH). Methods We searched multiple databases for studies published between January 1990 and December 2017. HBV infection (hepatitis B surface antigen) was diagnosed with serological assays. A random-effects meta-analysis served to pool data. Results We included 358 studies (834 544 PLWH from 87 countries). The pooled prevalence of HBV infection was 8.4% (95% confidence interval [CI], 7.9%–8.8%), among which 26.8% (95% CI, 22.0%–31.9%) was positive to hepatitis B e antigen. HBV prevalence (with 95% CIs) differed according to region: West and Central Africa, 12.4% (11.0%–13.8%); Middle East and North Africa, 9.9% (6.0%–14.6%); Asia and the Pacific, 9.8% (8.7%–11.0%); Eastern and Southern Africa, 7.4% (6.4%–8.4%); Western and Central Europe and North America, 6.0% (5.5%–6.7%); and Latin America and the Caribbean, 5.1% (4.2%–6.2%) (P <.0001). The prevalence decreased from 10.4% in low-developed to 6.6% in highly developed countries (P <.0001) and increased from 7.3% in countries with HIV prevalence ≤1% to 9.7% in countries with HIV prevalence >1% (P <.0001). Globally, we estimated that there were 3 136 500 (95% CI, 2 952 000–3 284 100) cases of HBV in PLWH, with 73.8% of estimated regional cases from sub-Saharan Africa and 17.1% from Asia and the Pacific. Conclusions This study suggests a high burden of HBV infection in PLWH, with disparities according to region, level of development, and country HIV prevalence. [ABSTRACT FROM AUTHOR]

Background: Little is known on the magnitude and correlates of insulin resistance in HIV-infected people in Africa. We determined the prevalence of insulin resistance and investigated associated factors in HIV-infected adult Cameroonians. Methods: We conducted a cross-sectional study at the Yaoundé Central Hospital, Cameroon; during which we enrolled HIV-infected people aged 30 to 74 years with no previous history of cardiovascular disease. An homeostatic model assessment of insulin resistance (HOMA-IR) like index served to assess insulin sensitivity with insulin resistance defined by values of 2.1 or higher. Results: We included 452 patients (20% men). Their mean age was 44.4 ± 9.8 years and 88.5% of them were on antiretroviral therapy (93.3% on first line regimen including Zidovudine, lamivudine and Efavirenz/Nevirapine). Of all participants, 28.5% were overweight, 19.5% had obesity and 2.0% had diabetes. The prevalence of insulin resistance was 47.3% without any difference between patients on ART and those ART-naïve (48.5% vs. 38.5%; p = 0.480). Obesity was the only factor independently associated with insulin resistance (adjusted odds ratio: 2.28; 95% confidence interval: 1.10-4.72). Conclusion: Insulin resistance is present in nearly half of HIV-infected patients in Cameroon despite a low prevalence rate of diabetes, and is associated with obesity. [ABSTRACT FROM AUTHOR]