• Comparison of Triple (AZT/3TC/EFV) Versus Quad (AZT/3TC/ABC/EFV) in ARV-Naive Patients With High Viral Load (>100 000 c/mL) Using a DAVG Analysis and a <5 c/mL VL Assay (Quad Study) (Poster 615)
  Authored by C. Orkin, on behalf of the Quad Study Group
  

A key debate in antiretroviral therapy is whether or not the current approaches to treatment are sufficiently potent. One reason for this debate is the continued ability to culture replication-competent virus even from patients with undetectable HIV RNA levels; another is the predicted long decay phase for the "latent reservoir" of HIV in resting cells. As a result, there has been ongoing interest in using more than three drugs for initial therapy, although studies so far have been disappointing due to excess drug toxicity and pill burden. The study presented here, comparing a standard triple-therapy regimen of AZT (zidovudine, Retrovir)/3TC (lamivudine, Epivir)/efavirenz (EFV, Sustiva) with a quadruple-drug regimen of AZT/3TC/abacavir (ABC, Ziagen)/efavirenz, used standard HIV RNA and CD4 measurements for monitoring, supplemented by an enhanced sensitivity HIV RNA test that measures down to 5 copies/mL and by special immunologic assays.

Fifty-three antiretroviral therapy-naive patients were enrolled. Baseline CD4 cell count was 155, HIV RNA 5.5 log. At the end of week 48, virologic responses were as follows:

For those patients who achieved the <5 copy level, there was no difference in time to <5 based on treatment assignment. In addition, there were no differences between the groups based on lymphoproliferative assays or intracellular cytokine staining. The AZT/3TC/ABC/efavirenz group had nine discontinuations for adverse effects, while the standard triple-therapy group had only three discontinuations because of adverse effects.

The results of this study, although small, suggest that the addition of abacavir does not appreciably enhance the antiviral potency of a standard triple-therapy regimen. In addition, the extra medication is likely to lead to more treatment discontinuations, offsetting any potential extra virologic benefits. Of note, Marty Markowitz (abstract 42) reported a similar problem with poor tolerability of AZT/3TC/ABC/efavirenz at this meeting. Until we hear the definitive results of the ongoing 5095 study -- which is still comparing AZT/3TC/efavirenz to AZT/3TC/ABC/efavirenz in a blinded fashion -- for now we likely should continue with a "less is more" approach when considering quadruple therapy.