Renal and metabolic toxicities following initiation of HIV-1 treatment regimen in a diverse, multinational setting: a focused safety analysis of ACTG PEARLS (A5175).

TitleRenal and metabolic toxicities following initiation of HIV-1 treatment regimen in a diverse, multinational setting: a focused safety analysis of ACTG PEARLS (A5175).
Publication TypeJournal Article
Year of Publication2014
AuthorsF Romo T, Smeaton LM, Campbell TB, Riviere C, Mngqibisa R, Nyirenda M, Supparatpinyo K, Kumarasamy N, Hakim JG, Flanigan TP
JournalHIV Clin Trials
Volume15
Issue6
Pagination246-60
Date Published2014 Nov-Dec
ISSN1528-4336
KeywordsAdult, Anti-HIV Agents, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Kidney Diseases, Logistic Models, Male, Metabolic Diseases, Middle Aged
Abstract

BACKGROUND: Convenient dosing, potency, and low toxicity support use of tenofovir disoproxil fumarate (TDF) as preferred nucleotide reverse transcriptase inhibitor (NRTI) for HIV-1 treatment. However, renal and metabolic safety of TDF compared to other NRTIs has not been well described in resource-limited settings.

METHODS: This was a secondary analysis examining the occurrence of renal abnormalities (RAs) and renal and metabolic serious non-AIDS-defining events (SNADEs) through study follow-up between participants randomized to zidovudine (ZDV)/lamivudine/ efavirenz and TDF/emtricitabine/efavirenz treatment arms within A5175/PEARLS trial. Exact logistic regression explored associations between baseline covariates and RAs. Response profile longitudinal analysis compared creatinine clearance (CrCl) over time between NRTI groups.

RESULTS: Twenty-one of 1,045 participants developed RAs through 192 weeks follow-up; there were 15 out of 21 in the TDF arm (P = .08). Age 41 years or older (odds ratio [OR], 3.35; 95% CI, 1.1-13.1), his- tory of diabetes (OR, 10.7; 95% CI, 2.1-55), and lower baseline CrCl (OR, 3.1 per 25 mL/min decline; 95% CI, 1.7-5.8) were associated with development of RAs. Renal SNADEs occurred in 42 participants; 33 were urinary tract infections and 4 were renal failure/insufficiency; one event was attributed to TDF. Significantly lower CrCl values were maintained among patients receiving TDF compared to ZDV (repeated measures analysis, P = .05), however worsening CrCl from baseline was not observed with TDF exposure over time. Metabolic SNADEs were rare, but were higher in the ZDV arm (20 vs 3; P < .001).

CONCLUSIONS: TDF is associated with lower serious metabolic toxicities but not higher risk of RAs, serious renal events, or worsening CrCl over time compared to ZDV in this randomized multinational study.

DOI10.1310/hct1506-246
Alternate JournalHIV Clin Trials
PubMed ID25433664
PubMed Central IDPMC4357257
Grant List2UMAI 069412-08 / / PHS HHS / United States
5T32DA013911 / DA / NIDA NIH HHS / United States
AI027661 / AI / NIAID NIH HHS / United States
AI034853 / AI / NIAID NIH HHS / United States
AI045008 / AI / NIAID NIH HHS / United States
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AI32782 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI50410 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
P30 AI042853 / AI / NIAID NIH HHS / United States
P30 AI042853 / AI / NIAID NIH HHS / United States
R000124 / / PHS HHS / United States
R000457 / / PHS HHS / United States
R00111 / / PHS HHS / United States
R25 MH083620 / MH / NIMH NIH HHS / United States
R25MH083620 / MH / NIMH NIH HHS / United States
RR024156 / RR / NCRR NIH HHS / United States
RR024160 / RR / NCRR NIH HHS / United States
T32 DA013911 / DA / NIDA NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
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UM1 AI069436 / AI / NIAID NIH HHS / United States
UM1AI068636 / AI / NIAID NIH HHS / United States