Simplification to abacavir/lamivudine + atazanavir maintains viral suppression and improves bone and renal biomarkers in ASSURE, a randomized, open label, non-inferiority trial.
OBJECTIVE
Simplification of antiretroviral therapy in patients with suppressed viremia may minimize long-term adverse effects. The study's primary objective was to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV) was virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC+ATV/r) over 24 weeks in a population of virologically suppressed, HIV-1 infected patients.


METHODS
This open-label, multicenter, non-inferiority study enrolled antiretroviral experienced, HIV-infected adults currently receiving a regimen of TDF/FTC+ATV/r for ≥ 6 months with no history of virologic failure and whose HIV-1 RNA had been ≤ 75 copies/mL on 2 consecutive measurements including screening. Patients were randomized 1 ∶ 2 to continue current treatment or simplify to ABC/3TC+ATV.


METHODS
The primary endpoint was the proportion of patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic Response (TLOVR) algorithm. Secondary endpoints included alternative measures of efficacy, adverse events (AEs), and fasting lipids. Exploratory endpoints included inflammatory, coagulation, bone, and renal biomarkers.


RESULTS
After 24 weeks, ABC/3TC+ATV (n = 199) was non-inferior to TDF/FTC+ATV/r (n = 97) by both the primary analysis (87% in both groups) and all secondary efficacy analyses. Rates of grade 2-4 AEs were similar between the two groups (40% vs 37%, respectively), but an excess of hyperbilirubinemia made the rate of grade 3-4 laboratory abnormalities higher in the TDF/FTC+ATV/r group (30%) compared with the ABC/3TC+ATV group (13%). Lipid levels were stable except for HDL cholesterol, which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers improved significantly between baseline and Week 24 in patients taking ABC/3TC+ATV, and the difference between groups was significant at Week 24. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups.


CONCLUSIONS
After 24 weeks, simplification to ABC/3TC+ATV from TDF/FTC+ATV/r maintained viral suppression was well-tolerated, and led to improvements in bone and renal biomarkers and HDL cholesterol.


BACKGROUND
ClinicalTrials.gov NCT01102972 GlaxoSmithKline Clinical Study Register #113734.
AIDS Clinical Trials Unit, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
David A
DA
Wohl
AIDS Healthcare Foundation, Beverly Hills, California, United States of America.
Laveeza
L
Bhatti
New York Medical College, Valhalla, New York, United States of America.
Catherine B
CB
Small
Alameda County Medical Center, Oakland, California, United States of America.
Howard
H
Edelstein
GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
Henry H
HH
Zhao
GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
David A
DA
Margolis
Orlando Immunology Center, Orlando, Florida, United States of America.
Edwin
E
DeJesus
Kaiser Foundation Health Plan of Georgia, Inc, Atlanta, Georgia, United States of America.
Winkler G
WG
Weinberg
ViiV Healthcare, Research Triangle Park, North Carolina, United States of America.
Lisa L
LL
Ross
ViiV Healthcare, Research Triangle Park, North Carolina, United States of America.
Mark S
MS
Shaefer
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D000069446:Atazanavir Sulfate; D015415:Biomarkers / Q000097:blood; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*; D055815:Young Adult; D000099227:Abacavir
D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D015415:Biomarkers; D015224:Dideoxynucleosides; D004338:Drug Combinations; D019259:Lamivudine; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir