title: Reduced renal function is associated with progression to AIDS but not with overall mortality in HIV-infected Kenyan adults not initially requiring combination antiretroviral therapy.
abstract: BACKGROUND
  The World Health Organization (WHO) has recently recommended that antiretrovirals be initiated in all individuals with CD4 counts of less than 350 cells/mm3. For countries with resources too limited to expand care to all such patients, it would be of value to able to identify and target populations at highest risk of HIV progression. Renal disease has been identified as a risk factor for disease progression or death in some populations.
  
  
  METHODS
  Times to meeting combination antiretroviral therapy (cART) initiation criteria (developing either a CD4 count < 200 cells/mm3 or WHO stage 3 or 4 disease) and overall mortality were evaluated in cART-naïve, HIV-infected Kenyan adults with CD4 cell counts ≥200/mm3 and with WHO stage 1 or 2 disease. Cox proportional hazard regression models were used to evaluate the associations between renal function and these endpoints.
  
  
  RESULTS
  We analyzed data of 7383 subjects with a median follow-up time of 59 (interquartile range, 27-97) weeks. In Cox regression analyses adjusted for age, sex, WHO disease stage, CD4 cell count and haemoglobin, estimated creatinine clearance (CrCl) < 60 mL/min was significantly associated with shorter times to meeting cART initiation criteria (HR 1.34; 95% CI, 1.23-1.52) and overall mortality (HR 1.73; 95% CI, 1.19-2.51) compared with CrCl ≥60 mL/min. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 was associated with shorter times to meeting cART initiation criteria (HR 1.39; 95% CI, 1.22-1.58), but not with overall mortality. CrCl and eGFR remained associated with shorter times to cART initiation criteria, but neither was associated with mortality, in weight-adjusted analyses.
  
  
  CONCLUSIONS
  In this large natural history study, reduced renal function was strongly associated with faster HIV disease progression in adult Kenyans not initially meeting cART initiation criteria. As such, renal function measurement in resource-limited settings may be an inexpensive method to identify those most in need of cART to prevent progression to AIDS. The initial association between reduced CrCl, but not reduced eGFR, and greater mortality was explained by the low weights in this population.
authors.affiliation: Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, IN, USA. sgupta1@iupui.edu
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Willis Owino
authors.initials: WO
authors.lastname: Ong'or
authors.forename: Changyu
authors.initials: C
authors.lastname: Shen
authors.forename: Beverly
authors.initials: B
authors.lastname: Musick
authors.forename: Mitchell
authors.initials: M
authors.lastname: Goldman
authors.forename: Kara
authors.initials: K
authors.lastname: Wools-Kaloustian
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D007630:Kenya; D007674:Kidney Diseases / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D012189:Retrospective Studies
chemical_list: D019380:Anti-HIV Agents