F Touzard Romo1, L M Smeaton2, T B Campbell3, C Riviere4, R Mngqibisa5, M Nyirenda6, K Supparatpinyo7, N Kumarasamy8, J G Hakim9, T P Flanigan1. 1. The Miriam Hospital, Providence, Rhode Island, USA Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. 2. Harvard School of Public Health, Boston, Massachusetts, USA. 3. University of Colorado Denver, Aurora, Colorado, USA. 4. Institut Nacional de Laboratoire et Recherches, Port-au-Prince, Haiti. 5. University of KwaZulu-Natal, Durban, South Africa. 6. College of Medicine - Johns Hopkins Research Project, Blantyre, Malawi. 7. Chiang Mai University, Chiang Mai, Thailand. 8. YRG Centre for AIDS Research and Education, Chennai, India. 9. University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
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.
RCT Entities:
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.
Authors: Joel E Gallant; Edwin DeJesus; José R Arribas; Anton L Pozniak; Brian Gazzard; Rafael E Campo; Biao Lu; Damian McColl; Steven Chuck; Jeffrey Enejosa; John J Toole; Andrew K Cheng Journal: N Engl J Med Date: 2006-01-19 Impact factor: 91.245
Authors: F J Palella; K M Delaney; A C Moorman; M O Loveless; J Fuhrer; G A Satten; D J Aschman; S D Holmberg Journal: N Engl J Med Date: 1998-03-26 Impact factor: 91.245
Authors: Rabi Yacoub; Girish N Nadkarni; Damian Weikum; Ioannis Konstantinidis; Anna Boueilh; Robert M Grant; Kenneth K Mugwanya; Jared M Baeten; Christina M Wyatt Journal: J Acquir Immune Defic Syndr Date: 2016-04-01 Impact factor: 3.731
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