Effect of Baseline Renal Function on Tenofovir-Containing Antiretroviral Therapy Outcomes in Zambia

• Published in: Clinical infectious diseases Vol. 58; no. 10; pp. 1473 - 1480
• Main Authors: Mulenga, Lloyd, Musonda, Patrick, Mwango, Albert, Vinikoor, Michael J., Davies, Mary-Ann, Mweemba, Aggrey, Calmy, Alexandra, Stringer, Jeffrey S., Keiser, Olivia, Chi, Benjamin H., Wandeler, Gilles
• Format: Journal Article
• Language: English
• Published: Oxford OXFORD UNIVERSITY PRESS 15.05.2014; Oxford University Press
• Series: Editor's choice
• Subjects: Adenine - adverse effects; Adenine - analogs & derivatives; Adenine - therapeutic use; Adult; AIDS; Anemia; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - adverse effects; Antiretrovirals; Antiviral agents; Biological and medical sciences; Creatinine - blood; Epidemiology; Female; Glomerular filtration rate; Glomerular Filtration Rate - drug effects; Health outcomes; HIV; HIV Infections - drug therapy; HIV Infections - physiopathology; HIV/AIDS; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Kidney - physiopathology; Kidney diseases; Kidneys; Male; Medical sciences; Medical treatment; Mortality; Mortality rates; Organophosphonates - adverse effects; Organophosphonates - therapeutic use; Pharmacology. Drug treatments; Regression analysis; Renal function; Renal Insufficiency - chemically induced; Renal Insufficiency - mortality; Tenofovir; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Zambia; Zambia; Africa; Lusaka Zambia; tenofovir; renal function; Zambia; Immunopathology; Purine nucleotide; Antiretroviral agent; Acyclic nucleotide; RNA-directed DNA polymerase; Renal function; Prognosis; Enzyme; Transferases; Enzyme inhibitor; AIDS; Organic phosphonate; Nucleotide analog; Immune deficiency; Infection; Tenofovir; Nucleotidyltransferases; Chemotherapy; Treatment; Reverse transcriptase inhibitor; Viral disease; Nucleoside analog; Antiviral
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciu117

Background. Although tenofovir disoproxil fumarate (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non–TDF-containing ART in Lusaka, Zambia. Methods. We included patients aged ≥16 years who started ART from 2007 onward, with documented baseline weight and serum creatinine. Renal dysfunction was categorized as mild (estimated glomerular filtration rate [eGFR], 60–89 mL/min), moderate (30–59 mL/min), or severe (<30 mL/min) according to the chronic kidney disease–epidemiology (CKD-EPI) formula. Differences in eGFR during ART were analyzed using linear mixed-effect models. The odds of developing moderate or severe eGFR decrease and mortality were assessed using logistic and competing risk regression, respectively. Results. We included 62 230 adults, of which 38 716 (62.2%) initiated a TDF-based regimen. The proportion with moderate or severe renal dysfunction at baseline was lower in the TDF than in the non-TDF group (1.9% vs 4.0%). Among patients with no or mild renal dysfunction, those receiving TDF were more likely to develop moderate (adjusted odds ratio, 3.11; 95% confidence interval, 2.52–3.87) or severe ( 2.43; 1.80–3.28) eGFR decrease, although the incidence in such episodes was low. Among patients with moderate or severe renal dysfunction at baseline, renal function improved independently of ART regimen, and mortality rates were similar in both treatment groups. Conclusions. TDF use did not attenuate renal function recovery or increase the mortality rate in patients with renal dysfunction. Further studies are needed to determine the role of routine renal function monitoring before and during ART use in Africa.