title: Reduced glomerular filtration rate but sustained virologic response in HIV/hepatitis B co-infected individuals on long-term tenofovir.
abstract: Reports have described a decrease in glomerular filtration rate (eGFR) associated with tenofovir disoproxil fumarate (TDF) use in HIV positive individuals. However, no study has examined renal function over a prolonged period in HIV/hepatitis B virus (HBV) co-infected patients. We assessed the long-term durability and toxicity of TDF in a cohort of 39 e antigen (eAg) positive co-infected patients commenced on TDF 245 mg daily either in addition to or as part of standard antiretroviral therapy. Immunological and virological parameters were followed to 260 weeks, with the median follow-up period being 251 weeks (range 69-290 weeks). eGFR was calculated using the Modification in Diet in Renal Disease equation. On treatment at 260 weeks, 88% (14/16) had HIV viral load <50 copies/mL, median CD4 count rose from 318 to 532 cells/mm(3), median alanine aminotransferase (ALT) fell from 61 IU/L to 42 IU/L, with 35% (7/20) having a normal ALT, median HBV DNA fell from 69 x 10(6) copies/mL to 500 copies/mL, with 75% (12/16) having an undetectable HBV DNA level and 55% (6/11) becoming eAg negative. Of those with detectable HBV DNA, none had TDF resistance mutations. The eGFR declined by 22.19 mL/min/1.73 mm(2) from baseline (P = 0.023) over this period, which was unaffected by protease inhibitor use, baseline CD4 count, ALT or HBV DNA level. Three patients discontinued TDF therapy due to renal dysfunction. In conclusion, TDF has sustained efficacy but is associated with a significant decline in eGFR. Further larger studies are required to clarify this observation.
authors.affiliation: Department of HIV Medicine, Chelsea and Westminster Hospital, London, UK. lionel.tan@nhs.net
authors.forename: L K K
authors.initials: LK
authors.lastname: Tan
authors.forename: Y
authors.initials: Y
authors.lastname: Gilleece
authors.forename: S
authors.initials: S
authors.lastname: Mandalia
authors.forename: A
authors.initials: A
authors.lastname: Murungi
authors.forename: D
authors.initials: D
authors.lastname: Grover
authors.forename: M
authors.initials: M
authors.lastname: Fisher
authors.forename: M
authors.initials: M
authors.lastname: Atkins
authors.forename: M
authors.initials: M
authors.lastname: Nelson
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000410:Alanine Transaminase; D000225:Adenine