ACTG 5202 is an ongoing 96-week Phase III 4-arm study of initial ART strategies. Patients were randomized to blinded abacavir/lamivudine or emtricitabine/tenofovir, and to open label atazanavir/ritonavir or efavirenz. Earlier this year, an interim analysis by the Data Safety and Monitoring Board noted higher rates of early virologic failure among abacavir/lamivudine recipients with baseline HIV RNA ≥100,000 copies/mL. This led to unblinding of the NRTI backbones of patients in this high baseline viral load stratum. The ACTG 5202 interim results were presented in August at the XVII International AIDS Conference in Mexico City.(1)
The study cohort comprises 1,858 patients, including 797 with HIV RNA ≥100,000 copies/mL at baseline. The primary virologic end point was time to virologic failure, defined as HIV RNA ≥1,000 copies/mL at 16-24 weeks or ≥200 copies/mL at ≥24 weeks. Among patients with baseline HIV RNA ≥100,000, time to virologic failure was significantly shorter for the abacavir/lamivudine recipients, and the rate of virologic failure was higher (14% among abacavir/lamivudine recipients vs 7% among emtricitabine/tenofovir recipients) (hazard ratio [HR] = 2.33; p = .0003). However, among patients who did achieve suppression of HIV RNA to <50 copies/mL (on 2 checks), there was no significant difference between groups in the rate of virologic rebound.
Additionally, patients who received abacavir/lamivudine had a shorter time to grade 3/4 adverse events (HR = 1.86; p < .0001), with a majority of reactions being generalized body aches and increased lipids. Rates of suspected abacavir hypersensitivity reaction were the same in both NRTI groups and did not appear to explain the differences in rates of virologic failure.
Applying the same efficacy and safety end points as the ACTG 5202 study, researchers from GlaxoSmithKline (the manufacturer of abacavir and lamivudine) analyzed results of 6 clinical trials that used abacavir/lamivudine as an NRTI backbone.(2) They found no significant differences in rates of virologic failure between patients with baseline HIV RNA ≥100,000 copies/mL and those with <100,000 copies/mL. Their analysis included the HEAT study, which compared abacavir/lamivudine directly with tenofovir/emtricitabine (both combined with lopinavir/ritonavir) and found no significant differences in rates of virologic failure between the NRTI backbones among patients with high pretreatment viral loads. It should be noted, though, that these studies involved small numbers of patients with high viral loads and may be limited in their ability to discern the same differences in response.
| Clinical Bottom Line|
Even as the ACTG 5202 interim results undergo further scrutiny, clinicians should be cautious in initiating abacavir/lamivudine for patients with high baseline viral loads, particularly those for whom tenofovir/emtricitabine is an appropriate alternative.
The DHHS Adults and Adolescents Antiretroviral Treatment Guidelines Panel considers both abacavir/lamivudine and tenofovir/emtricitabine "preferred" NRTI components of initial ARV therapy.
- Sax P, Tierney C, Collier A, et al. ACTG 5202: shorter time to virologic failure (VF) with abacavir/lamivudine (ABC/3TC) than tenofovir/emtricitabine (TDF/FTC) as part of combination therapy in treatment-naive subjects with screening HIV RNA ≥100,000 c/mL. In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City. Abstract THAB0303.
- Pappa K, Hernandez J, Ma B, et al. Abacavir/lamivudine (ABC/3TC) shows robust virologic responses in ART-naive patients for baseline (BL) viral loads (VL) of ≥100,000c/mL and <100,000c/mL by endpoint used in ACTG5202. In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City. Abstract THAB0304.