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

Philip Grant, Camlin Tierney, Chakra Budhathoki, Eric Daar, Paul Sax, Ann Collier, Margaret A Fischl, Andrew Zolopa, Maya Balamane, David Katzenstein

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 log<sub>10</sub> 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.

Original languageEnglish
Pages (from-to)284-291
Number of pages8
JournalHIV Clinical Trials
Volume14
Issue number6
DOIs
StatePublished - Jan 1 2013

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Tenofovir
Viral Load
efavirenz
Lamivudine
Ritonavir
Nonparametric Statistics
lamivudine drug combination abacavir
Emtricitabine

Keywords

  • anti-HIV agents
  • drug therapy
  • HIV infections
  • treatment outcome
  • virology

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Grant, P., Tierney, C., Budhathoki, C., Daar, E., Sax, P., Collier, A., ... Katzenstein, D. (2013). Early virologic response to abacavir/lamivudine and tenofovir/emtricitabine during ACTG A5202. HIV Clinical Trials, 14(6), 284-291. https://doi.org/10.1310/hct1406-284

Early virologic response to abacavir/lamivudine and tenofovir/emtricitabine during ACTG A5202. / Grant, Philip; Tierney, Camlin; Budhathoki, Chakra; Daar, Eric; Sax, Paul; Collier, Ann; Fischl, Margaret A; Zolopa, Andrew; Balamane, Maya; Katzenstein, David.

In: HIV Clinical Trials, Vol. 14, No. 6, 01.01.2013, p. 284-291.

Research output: Contribution to journalArticle

Grant, P, Tierney, C, Budhathoki, C, Daar, E, Sax, P, Collier, A, Fischl, MA, Zolopa, A, Balamane, M & Katzenstein, D 2013, 'Early virologic response to abacavir/lamivudine and tenofovir/emtricitabine during ACTG A5202', HIV Clinical Trials, vol. 14, no. 6, pp. 284-291. https://doi.org/10.1310/hct1406-284
Grant, Philip ; Tierney, Camlin ; Budhathoki, Chakra ; Daar, Eric ; Sax, Paul ; Collier, Ann ; Fischl, Margaret A ; Zolopa, Andrew ; Balamane, Maya ; Katzenstein, David. / Early virologic response to abacavir/lamivudine and tenofovir/emtricitabine during ACTG A5202. In: HIV Clinical Trials. 2013 ; Vol. 14, No. 6. pp. 284-291.
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abstract = "Background: ACTG A5202 randomized treatment-na{\"i}ve 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.",
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AU - Daar, Eric

AU - Sax, Paul

AU - Collier, Ann

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