Early virologic response to abacavir/lamivudine and tenofovir/emtricitabine during ACTG A5202.

TitleEarly virologic response to abacavir/lamivudine and tenofovir/emtricitabine during ACTG A5202.
Publication TypeJournal Article
Year of Publication2013
AuthorsGrant PM, Tierney C, Budhathoki C, Daar ES, Sax PE, Collier AC, Fischl MA, Zolopa AR, Balamane M, Katzenstein D
JournalHIV Clin Trials
Volume14
Issue6
Pagination284-91
Date Published2013 Nov-Dec
ISSN1528-4336
KeywordsAdenine, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Deoxycytidine, Dideoxynucleosides, Drug Combinations, Drug Therapy, Combination, Emtricitabine, Female, HIV Infections, Humans, Lamivudine, Male, Middle Aged, Organophosphonates, Tenofovir, Viral Load
Abstract

BACKGROUND: ACTG A5202 randomized treatment-naïve individuals to tenofovir-emtricitabine (TDF/FTC) or abacavir-lamivudine (ABC/3TC) combined with efavirenz (EFV) or atazanavir/ritonavir (ATV/r). Individuals in the high screening viral load (VL) stratum (≥100,000 copies/mL) had increased rates of virologic failure with ABC/3TC.

OBJECTIVE: To compare regimen-specific early virologic response.

METHODS: Using Wilcoxon rank-sum tests, we compared regimen-specific VL changes from entry to week 4 in A5202 subjects (N = 1,813) and from entry to week 1, 2, and 4 in substudy subjects (n = 179). We evaluated associations between week 4 VL change and time to virologic failure with Cox proportional hazards models.

RESULTS: TDF/FTC and ABC/3TC produced similar week 4 VL declines in the entire study population and in the high VL stratum. EFV produced greater VL declines from baseline at week 4 than ATV/r (median -2.1 vs -1.9 log10 copies/mL; P < .001). In the substudy of subjects with week 1, 2, and 4 VL data, there was no difference in VL decline in individuals randomized to TDF/FTC versus ABC/3TC, but EFV resulted in greater VL decline from entry at each of these timepoints than ATV/r. Smaller week 4 VL decline was associated with increased risk of virologic failure.

CONCLUSIONS: Within all treatment arms, a less robust week 4 virologic response was associated with higher risk for subsequent virologic failure. However, between-regimen differences in week 4 VL declines did not parallel the previously reported differences in longer term virologic efficacy in A5202, suggesting that between-regimen differences in responses were not due to intrinsic differences in antiviral activity.

DOI10.1310/hct1406-284
Alternate JournalHIV Clin Trials
PubMed ID24334181
PubMed Central IDPMC4060613
Grant ListAI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UL1 RR024996 / RR / NCRR NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069477 / AI / NIAID NIH HHS / United States