Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency Virus and Hepatitis B Virus (HBV)-Coinfected Patients With High HBV Replication.

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 HIV-infected 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. Clinical Trials Registration: NCT00495651.

Clinical Outcomes during Treatment Interruptions in Human Immunodeficiency Virus-Hepatitis B Virus Co-infected Patients from Sub-Saharan Africa.

Antiretroviral treatment (ART) interruptions increase the risk of severe morbidity/mortality in human immunodeficiency virus (HIV)-infected individuals from subSaharan Africa. We aimed to determine whether the risk is further increased among HIV-hepatitis B virus (HBV) co-infected patients in this setting. In this sub-analysis of a randomized-control trial, 632 participants from Côte d'Ivoire randomized to receive continuous-ART (C-ART), structured ART interruptions of 2-months off, 4-months on (2/4-ART), and CD4-guided ART interruptions (CD4GT, interruption at 350/mm3 and reintroduction at 250/mm3) were analyzed. Incidence rates (IR) of serious HIV- and non-HIV-related morbidity were compared between patients stratified on hepatitis B surface antigen (HBsAg) status. Overall, 65 (10.3%) were HBsAg-positive, 29 (44.6%) of whom had HBV-DNA levels > 10,000 copies/mL. After a median 2.0 year (range = 0.2-3.1) follow-up, ≥ 1 serious HIV-related events occurred in 101 HIV mono-infected and 15 HIV-HBV co-infected patients (IR = 10.0 versus 13.2/100 person/years, respectively, P = 0.3), whereas the highest incidence was observed in co-infected patients with baseline HBV-replication > 10,000 copies/mL (IR = 24.0/100 person/years, P versus HIV mono-infected = 0.002). Incidence of bacterial infections was also highest in the co-infected group with HBV-replication > 10,000 copies/mL (IR = 12.9 versus 3.3/100 person/years in HIV mono-infected patients, P = 0.001). The relative effect of CD4GT or 2/4-ART versus C-ART was not different between infection groups (P for interaction = 0.4). No increase in the incidence of non-HIV-related morbidity was observed for co-infected patients (P = 0.5), even at HBV-replication levels > 10,000 copies/mL (P = 0.7). In conclusion, co-infected patients with elevated HBV-replication at ART-initiation are more susceptible to HIV-related morbidity, especially invasive bacterial diseases, during treatment interruption.

African, Amerindian and European hepatitis B virus strains circulate on the Caribbean Island of Martinique.

Ten Hepatitis B virus (HBV) genotypes, as well as numerous subgenotypes, have been described in well-characterized ethnogeographical populations. Martinique has been at a crossroads between Africa, Europe, India and the Americas because of the slave trade (17th-19th centuries), followed by an important immigration of Indian and West African workers. In this work, we aimed to study the molecular epidemiology of HBV infection in Martinique according to this unique settlement pattern. To that end, blood samples from 86 consecutive HBV-infected patients from the main hospitals of the island, were retrospectively analysed. Direct sequencing of the pre-S1 or pre-C-C region or complete genome sequencing, followed by phylogenetic analyses were performed. HBV genotypes were: HBV/A1 (68.6 %), HBV/A2 (10.5 %), HBV/D, mainly HBV/D3 and HBV/D4 (8.1 %), HBV/F (3.5 %), and also HBV/E (2.3 %), two strains isolated from two West-African patients. Moreover, 74 % of the HBeAg-negative strains harboured classical pre-C-C mutations, and most HBV/A1 strains also containing specific mutations. Finally, various patterns of deletion mutants in pre-S and pre-C-C regions were found. In conclusion, our findings point to historical and migration-related issues in HBV-genotype distribution suggesting that HBV/A1, but not HBV/E, was imported from Africa during the slave trade, and further supporting the hypothesis that HBV/E has emerged recently in West Africa (<150 years). Potential origins of 'European' HBV/A2 and HBV/D3, 'Amerindian' HBV/F, and HBV/D4 strains are also discussed. Such HBV genetic diversity, beyond its epidemiological interest, may have a clinical impact on the natural history of HBV infection in Martinique.

Prevalence, risk factors, and molecular epidemiology of hepatitis B and hepatitis delta virus in pregnant women and in patients in Mauritania.

No recent data are available on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) prevalence in Mauritania. One thousand twenty pregnant women and 946 patients visiting for routine checkups were screened for HBV and HDV infection. Demographic, epidemiological, ethnic, clinical, and biological data were recorded. HBV and HDV genotypes were determined by sequencing and phylogenetic analyses. In the pregnant women and patients cohorts, respectively, the prevalence of HBsAg (10.7% and 18.3%) and anti-HBcAb (66.3% and 76.5%) indicated high HBV endemicity. In pregnant women, exposure to HBV was significantly associated in multivariate analysis with education level, ethnicity, blood transfusion, and occupation. HDV antibodies (HDVAb) were found in 14.7% of pregnant women. In patients, HBsAg was found less frequently in females than in males. Again in multivariate analysis, exposure to HBV was significantly correlated with gender (males), and HDVAb positivity with age and gender. The HBV DNA viral load was >3 log IU/ml in only 10.1% of pregnant women and in 17.3% of patients. HDV-RNA was detectable in 21 (67.7%) of the 31 patients positive for HDVAb, and in 11 of the 16 pregnant women positive for HDVAb (68.8%). The most frequent HBV genotypes were: HBV/D, 53%; HBV/E, 35%; and HBV/A, 12%. Sub-genotyping revealed HBV/D1,/D7, and the recently described/D8. HDV genotypes were: HDV-1, 90.3% and HDV-5, 9.7%. This study confirms the high prevalence of HBV and HDV infections in Mauritania and demonstrates the high genetic diversity of HBV in this country.