The ASSURE Study: HIV-1 Suppression is Maintained with Bone and Renal Biomarker Improvement 48 Weeks After Ritonavir Discontinuation and Randomized Switch to Abacavir/lamivudine + atazanavir

Overview

Journal HIV Med

Publisher Wiley

Specialty Infectious Diseases

Date 2015 Jul 16

PMID 26176344

Citations 7

Authors

D A Wohl

L Bhatti

C B Small

H Edelstein

H H Zhao

D A Margolis

E DeJesus

W G Weinberg

L L Ross

M S Shaefer

Affiliations

Soon will be listed here.

Abstract

Objectives: HIV treatment guidelines endorse switching or simplification of antiretroviral therapy in therapy-experienced patients with suppressed viraemia; ritonavir discontinuation may also enhance tolerability and reduce long-term adverse events (AEs). This open-label, multicentre, noninferiority study enrolled HIV-1-infected, treatment-experienced adults with confirmed HIV-1 RNA ≤ 75 HIV-1 RNA copies/mL currently receiving tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC + ATV/r) for ≥ 6 months with no reported history of virological failure.

Methods: Participants were randomized 1:2 to continue current treatment or switch to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Endpoints included the proportion of participants with HIV-1 RNA < 50 copies/mL by time to loss of virological response (TLOVR), AEs, fasting lipids, and inflammatory, coagulation, bone and renal biomarkers.

Results: After 48 weeks, 76% (152 of 199) of ABC/3TC + ATV-treated and 79% (77 of 97) of TDF/FTC + ATV/r-treated participants had HIV-1 RNA < 50 copies/mL (TLOVR; P = 0.564). Other efficacy analyses yielded similar results. Rates of new grade 2-4 AEs were 45% in both groups, but an excess of hyperbilirubinaemia made the rate of treatment-emergent grade 3-4 laboratory abnormalities higher with TDF/FTC + ATV/r (36%) compared with ABC/3TC + ATV (19%). Most fasting lipid levels remained stable over time; high-density lipoprotein (HDL) cholesterol increased modestly in ABC/3TC + ATV-treated participants. Bone and renal biomarkers improved significantly between baseline and week 48 in participants taking ABC/3TC + ATV and were stable in participants taking TDF/FTC + ATV/r. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups.

Conclusions: The ABC/3TC + ATV treatment-switch group had similar viral suppression rates up to 48 weeks to the TDF/FTC + ATV/r comparator group, with lower rates of moderate- to high-grade hyperbilirubinaemia and improvements in bone and renal biomarkers.

Citing Articles

Bone Quality in Relation to HIV and Antiretroviral Drugs.

Olali A, Carpenter K, Myers M, Sharma A, Yin M, Al-Harthi L Curr HIV/AIDS Rep. 2022; 19(5):312-327.

PMID: 35726043 PMC: 10309294. DOI: 10.1007/s11904-022-00613-1.

Bone turnover markers in children living with HIV remaining on ritonavir-boosted lopinavir or switching to efavirenz.

Shiau S, Yin M, Strehlau R, Shen J, Abrams E, Coovadia A Bone. 2020; 138:115500.

PMID: 32590137 PMC: 8786259. DOI: 10.1016/j.bone.2020.115500.

GG attenuates tenofovir disoproxil fumarate-induced bone loss in male mice gut-microbiota-dependent anti-inflammation.

Liu H, Gu R, Li W, Zhou W, Cong Z, Xue J Ther Adv Chronic Dis. 2019; 10:2040622319860653.

PMID: 31321013 PMC: 6610433. DOI: 10.1177/2040622319860653.

Robertson K, Maruff P, Ross L, Wohl D, Small C, Edelstein H J Neurovirol. 2018; 25(1):22-31.

PMID: 30298202 PMC: 6416234. DOI: 10.1007/s13365-018-0680-y.

Bone Loss in HIV Infection.

Moran C, Weitzmann M, Ofotokun I Curr Treat Options Infect Dis. 2017; 9(1):52-67.

PMID: 28413362 PMC: 5388454. DOI: 10.1007/s40506-017-0109-9.

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