title: Tenofovir use and renal insufficiency among pregnant and general adult population of HIV-infected, ART-naïve individuals in Lilongwe, Malawi.
abstract: BACKGROUND
  The Malawian government recently changed its prevention of mother-to-child transmission (PMTCT) regimen and plans to change its first-line antiretroviral therapy (ART) regimen to Tenofovir(TDF)/Lamivudine/Efavirenz as a fixed-dose combination tablet. Implementation could be challenging if baseline creatinine clearance (CrCl) screening were required to assess renal function prior to TDF therapy. Our goal is to determine predictors of CrCl<50 ml/min among HIV-infected, ART-naïve individuals.
  
  
  METHODS
  Data on HIV-infected, ART-naïve adults screened for enrollment into 5 HIV clinical trials in Lilongwe, Malawi were combined for a pooled analysis of predictors for CrCl<50 ml/min. CrCl was derived from the Cockroft-Gault equation. Multivariable logistic regression modeled the association of age, body mass index (BMI), hemoglobin, CD4 cell count <350 cells/mm(3), gender, and pregnancy with CrCl<50 ml/min.
  
  
  RESULTS
  The analysis included 3508 patients with values for creatinine clearance. Most subjects were female (90.6%) with a median age of 26 years (IQR 22-29). The median CD4 cell count was 444 (IQR 298.0-561.0), and 85.2% percent of women in our study were pregnant. Few patients had CrCl<50 ml/min (n = 38, 1.1%). A BMI less than 18.5 in non-pregnant females (OR = 8.87, 95% CI = 2.45-32.09)) was associated with CrCl<50 ml/min. Hemoglobin level higher than 10 g/dL in males (OR = 0.69, 95% CI = 0.56-0.86) and non-pregnant females (OR = 0.21, 95% CI = 0.04-0.97) was protective against CrCl<50 ml/min.
  
  
  CONCLUSIONS
  Our findings indicate few patients would be excluded from a TDF-based antiretroviral regimen, suggesting baseline creatinine clearance assessment may not be necessary for implementation. However, in ART settings individuals with low BMI or anemia could potentially be at increased risk for lower CrCl.
authors: University of North Carolina Project Malawi, Lilongwe, Malawi. Frg1@uab.edu
authors: Derek C
authors: DC
authors: Johnson
authors: Charles
authors: C
authors: Chasela
authors: Madalitso
authors: M
authors: Maliwichi
authors: Albert
authors: A
authors: Mwafongo
authors: Adesola
authors: A
authors: Akinkuotu
authors: Agness
authors: A
authors: Moses
authors: Denise J
authors: DJ
authors: Jamieson
authors: Athena P
authors: AP
authors: Kourtis
authors: Caroline C
authors: CC
authors: King
authors: Charlie
authors: C
authors: van der Horst
authors: Mina C
authors: MC
authors: Hosseinipour
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D003404:Creatinine / Q000652:urine; D003521:Cyclopropanes; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000652:urine; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D008295:Malawi / Q000453:epidemiology; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000652:urine; D051437:Renal Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology / Q000652:urine; D000068698:Tenofovir
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D063065:Organophosphonates; D019259:Lamivudine; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine; C098320:efavirenz