Epidemiology of HBV infection in a cohort of Ugandan HIV-infected patients and rate and pattern of lamivudine-resistant HBV infection in patients receiving antiretroviral therapy Giorgio Calisti a, *, Rose Muhindo b , Yap 2nd Boum c , Laurence A. Wilson b , Geraldine M. Foster d , Anna Maria Geretti d and Sanjay Bhagani e a Department of Virology, Royal Free London NHS Foundation Trust, London, UK; b Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; c Epicentre Mbarara Research Base, Mbarara, Uganda; d Institute of Infection and Global Health, University of Liverpool, Liverpool, UK; e Department of HIV Medicine, Royal Free London NHS Foundation Trust,London, UK *Corresponding author: Tel: +44 20 7794 0500, ext. 34089; E-mail: giorgiocalisti@gmail.com; giorgio.calisti@nhs.net Received 11 July 2015; revised 20 August 2015; accepted 21 August 2015 Background: Many HIV-infected patients in sub-Saharan Africa are not routinely screened for hepatitis B virus (HBV) infection and are on antiretroviral therapy (ART) regimens containing only lamivudine as anti-HBV active drug. Methods: In 2009-2011, we screened for hepatitis B surface antigen (HBsAg) in 2820 HIV-infected adults patients at the Mbarara Hospital Uganda and investigated risk factors for HBV infection. Using samples of dried plasma or blood spots, we tested for HBV viral load and HBV drug resistance mutations in all HBsAg-positive patients on ART for ≥12 months. Results: In this study, 109 patients tested HBsAg positive (3.9%; 109/2820). HBsAg-positive patients were more likely to have had .4 lifetime sexual partners (p,0.01). Of the 55 HBsAg-positive patients on ART for ≥12 months, 53 were only on lamivudine as anti-HBV active drug and two were on tenofovir and lamivudine. HBV- DNA was detected in 30 patients (54.5%; 30/55), all on lamivudine-monotherapy. Of the 23 patients in whom HBV-DNA sequencing was successful, 17 had lamivudine-resistant HBV strains harbouring rtM204V/I mutations accompanied by secondary/compensatory mutations. Conclusions: Our study suggests that sexual transmission may represent a major mode of spread of HBV in southwest Uganda and confirms the importance of screening for HBV and of using ART regimens containing tenofovir in HIV/HBV co-infected patients. Keywords: Epidemiology, HBV, HIV, Lamivudine, Resistance, Sub-Saharan Africa Introduction Co-infection with hepatitis B virus (HBV) and HIV is common in sub-Saharan Africa, where both viruses are highly endemic. 1 With a hepatitis B surface antigen (HBsAg) prevalence rate of 10.3% in the general population, in Uganda there are approxi- mately 1.8 million adults infected with HBV, while the number of HIV-infected adults is around 1.4 million. 2–4 In Uganda, there are limited data on the prevalence of HBV co-infection among people living with HIV/AIDS. In the national hepatitis B sero-survey incorporated into the 2005 Uganda HIV/AIDS sero-behavioural survey (UHSBS), prevalence of HBsAg-positivity among adults liv- ing with HIV/AIDS was 8.3%, which was not significantly different from the prevalence rate in the HIV-negative population. 2 This study also found marked variations in the rates of current and past hepatitis B infections in the different regions of Uganda, with the northeastern region having a six-fold higher prevalence of HBsAg-positivity compared to the southwestern region (23.9% vs 3.8%). 2 HIV infection exerts a negative impact on the course of HBV infection at various levels. In HIV-infected individuals, hepatitis B is more likely to progress to chronicity after an acute infection, HBV DNA blood levels tend to be higher, rates of hepatitis B e anti- gen (HBeAg) loss are lower, progression to end-stage liver disease is accelerated and the risk of hepatocellular carcinoma and liver- related mortality is increased. 5 Furthermore, when choosing the combination of antiretroviral drugs (ARVs) for patients with HIV/ HBV co-infection, it is important to consider that some of these agents have dual activity against both viruses and that HBV is able to develop resistance to lamivudine (LAMr) at rates of 20% # The Author 2015. Published by Oxford University Press on behalf of Royal Societyof Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. ORIGINAL ARTICLE Trans R Soc Trop Med Hyg 2015; 109: 723–729 doi:10.1093/trstmh/trv077 Advance Access publication 18 September 2015 723 at MSF Cdoc on October 23, 2015 http://trstmh.oxfordjournals.org/ Downloaded from