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.
