Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia

Background Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. Methods We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. Results Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1–9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3–13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192–8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22–5.53) and CD4 cell count below 200/μl (2.58, 1.20–5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. Conclusion One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults.

[1]  B. Chi,et al.  Corrigendum to “Hepatitis B viral load in dried blood spots: A validation study in Zambia” [J. Clin. Virol. 72 (2015) 20–24] , 2016 .

[2]  B. Chi,et al.  Hepatitis B viral load in dried blood spots: A validation study in Zambia. , 2015, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[3]  T. Ndung’u,et al.  Prevalence and Characteristics of Hepatitis B Virus (HBV) Coinfection among HIV-Positive Women in South Africa and Botswana , 2015, PloS one.

[4]  R. Kahn,et al.  Prevalence of HIV and Hepatitis B Virus Co-Infection in Sub-Saharan Africa and the Potential Impact and Program Feasibility of Hepatitis B Surface Antigen Screening in Resource-Limited Settings , 2015, Journal of acquired immune deficiency syndromes.

[5]  G. Cooke,et al.  Analysis of minimum target prices for production of entecavir to treat hepatitis B in high- and low-income countries , 2015, Journal of virus eradication.

[6]  Mark Hopkins,et al.  Hepatitis B virus sub-genotype A1 infection is characterized by high replication levels and rapid emergence of drug resistance in HIV-positive adults receiving first-line antiretroviral therapy in Malawi. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  M. Egger,et al.  Hepatitis B virus infection is associated with impaired immunological recovery during antiretroviral therapy in the Swiss HIV cohort study. , 2013, The Journal of infectious diseases.

[8]  T. F. Rinke de Wit,et al.  HIV–HBV Coinfection in Southern Africa and the Effect of Lamivudine- Versus Tenofovir-Containing cART on HBV Outcomes , 2013, Journal of acquired immune deficiency syndromes.

[9]  R. Byrne,et al.  Tenofovir-based combination therapy for HIV/HBV co-infection: factors associated with a partial HBV virological response in patients with undetectable HIV viraemia , 2013, AIDS.

[10]  W. Fawzi,et al.  Prevalence of hepatitis B co-infection and response to antiretroviral therapy among HIV-infected patients in Tanzania , 2013, AIDS.

[11]  K. Mandaliya,et al.  Prevalence, Clinical and Virologic Outcomes of Hepatitis B Virus Co-Infection in HIV-1 Positive Kenyan Women on Antiretroviral Therapy , 2013, PloS one.

[12]  Z. Fox,et al.  Outcomes of starting first-line antiretroviral therapy in hepatitis B virus/HIV-coinfected patients in Ghana. , 2012, The Journal of antimicrobial chemotherapy.

[13]  Kara Wools-Kaloustian,et al.  Cohort Profile: the international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa. , 2012, International journal of epidemiology.

[14]  A. Kramvis,et al.  Genotyping and Molecular Characterization of Hepatitis B Virus from Human Immunodeficiency Virus-Infected Individuals in Southern Africa , 2012, PloS one.

[15]  D. Hillyard,et al.  Development and validation of a hepatitis B virus DNA sequencing assay for assessment of antiviral resistance, viral genotype and surface antigen mutation status. , 2011, Journal of virological methods.

[16]  B. Chi,et al.  HIV, Hepatitis B, and Hepatitis C in Zambia , 2011, Journal of global infectious diseases.

[17]  E. Bottieau,et al.  Seroprevalence of transfusion-transmissible infections and evaluation of the pre-donation screening performance at the Provincial Hospital of Tete, Mozambique , 2011, BMC infectious diseases.

[18]  R. Barth,et al.  Hepatitis B/C and HIV in sub-Saharan Africa: an association between highly prevalent infectious diseases. A systematic review and meta-analysis. , 2010, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[19]  C. Thio,et al.  Impact of hepatitis B virus infection on human immunodeficiency virus response to antiretroviral therapy in Nigeria. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  T. Luedde,et al.  The rtA194T polymerase mutation impacts viral replication and susceptibility to tenofovir in hepatitis B e antigen–positive and hepatitis B e antigen–negative hepatitis B virus strains , 2009, Hepatology.

[21]  Jörg Petersen,et al.  EASL Clinical Practice Guidelines: management of chronic hepatitis B. , 2009, Journal of hepatology.

[22]  R. Chaisson,et al.  Hepatitis B virus infection and response to antiretroviral therapy (ART) in a South African ART program. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  P. Ingrand,et al.  Use of replacement blood donors to study the epidemiology of major blood‐borne viruses in the general population of Maputo, Mozambique , 2007, Journal of medical virology.

[24]  R. Chaisson,et al.  Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B , 2007, AIDS.

[25]  Michael D. Miller,et al.  Intracellular Metabolism and In Vitro Activity of Tenofovir against Hepatitis B Virus , 2006, Antimicrobial Agents and Chemotherapy.

[26]  M. Helm,et al.  Variant of hepatitis B virus with primary resistance to adefovir. , 2006, The New England journal of medicine.

[27]  M. Alter,et al.  Epidemiology of viral hepatitis and HIV co-infection. , 2006, Journal of hepatology.

[28]  F. Tacke,et al.  Selection of Hepatitis B Virus Polymerase Mutations in HIV-Coinfected Patients Treated with Tenofovir , 2005, Antiviral therapy.

[29]  A. Valleron,et al.  Long-term hepatitis B virus dynamics in HIV–hepatitis B virus-co-infected patients treated with tenofovir disoproxil fumarate , 2005, AIDS.

[30]  J. Villeneuve,et al.  Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir , 2005, Hepatology.

[31]  Yunjeong Jang,et al.  Susceptibility to Antivirals of a Human HBV Strain with Mutations Conferring Resistance to Both Lamivudine and Adefovir. Hepatology 2005;41:1391-1398 , 2005 .

[32]  J. Kalbfleisch,et al.  A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C , 2003, Hepatology.