title: HIV-HBV coinfection in Southern Africa and the effect of lamivudine- versus tenofovir-containing cART on HBV outcomes.
abstract: BACKGROUND
  This study assessed HIV-hepatitis B virus (HBV) coinfection in southern Africa in terms of prevalence, viral characteristics, occult HBV, and the effect of lamivudine- versus tenofovir-containing first-line combination antiretroviral treatment (cART) on HBV-related outcomes.
  
  
  METHODS
  A multicenter prospective cohort of HIV-infected adults in Zambia and South Africa who initiated cART. Outcomes by month 12 on cART were immunological recovery, hepatitis B surface antigen (HBsAg) loss, viral suppression, and drug resistance. We used descriptive statistics, logistic regression, and linear mixed models.
  
  
  RESULTS
  Of the 1087 participants, 92 were HBsAg seropositive, yielding a sample-weighted prevalence of 7.4% (95% confidence interval: 5.6 to 9.2), with 76% genotype HBV-A1. The estimated CD4 recovery on cART was similar between HIV monoinfection and HIV-HBV coinfection groups and between lamivudine- and tenofovir-treated participants. HBsAg loss was documented in 20% (4/20) of lamivudine-treated and 18% (3/17) of tenofovir-treated participants (P = 0.305). Viral suppression (HBV-DNA < 20 IU/mL) was achieved in 61.5% (16/26) of lamivudine-treated and 71.4% (15/21) of tenofovir-treated participants (P = 0.477). HBV pol sequencing demonstrated M204I (n = 3) and N236T (n = 1) resistance-associated mutations in 4 of 8 (50%) lamivudine-treated participants and none in tenofovir-treated participants. Occult HBV infection was present in 13.3% before cART, but by month 12, HBV-DNA was below the limit of detection (<15 IU/mL) in 90.5% (19/21) of lamivudine-treated and 100% (18/18) of tenofovir-treated participants (P = 0.179).
  
  
  CONCLUSIONS
  Tenofovir-containing first-line cART is preferred for HIV-HBV coinfection in Africa because of a superior resistance profile relative to lamivudine monotherapy. Extended follow-up will be needed to determine long-term complications of occult HBV coinfection. Improved access to HBsAg screening and tenofovir is needed.
authors.affiliation: *Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands; †PharmAccess Foundation, Amsterdam, The Netherlands; ‡Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands; §Department of Blood-Borne Infections, Sanquin, Amsterdam, The Netherlands; ‖Department of Medical Microbiology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands; ¶Department of Molecular Medicine and Hematology, University of the Witwatersrand, Johannesburg, South Africa; #Lancet Laboratories, Johannesburg, South Africa; **Lusaka Trust Hospital, Lusaka, Zambia; ††Clinical HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa; ‡‡Muelmed Hospital, Pretoria, South Africa; and §§Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Raph L
authors.initials: RL
authors.lastname: Hamers
authors.forename: Hans L
authors.initials: HL
authors.lastname: Zaaijer
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Margaret
authors.initials: M
authors.lastname: Siwale
authors.forename: Prudence
authors.initials: P
authors.lastname: Ive
authors.forename: Mariette E
authors.initials: ME
authors.lastname: Botes
authors.forename: Kim C E
authors.initials: KC
authors.lastname: Sigaloff
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
authors.forename: Tobias F
authors.initials: TF
authors.lastname: Rinke de Wit
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006509:Hepatitis B / Q000150:complications* / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D013019:South Africa; D000068698:Tenofovir; D016896:Treatment Outcome; D015024:Zambia / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine