1. Home>
2. Specialties>
3. HIV/AIDS Clinical Care>
4. Research Notes

Abacavir vs. Indinavir

When combined with AZT/3TC, abacavir was less effective than indinavir among antiretroviral-naive patients with baseline viral loads >100,000 copies/ml.

Although therapy with at least 3 active drugs has been standard of care for HIV-infected patients for several years, few prospective, randomized trials comparing different treatment strategies have been published. This randomized, double-blind, placebo-controlled, manufacturer-sponsored equivalency study compared abacavir with indinavir, both combined with AZT/3TC in antiretroviral-naive patients.

Between August 1997 and June 1998, researchers recruited 562 patients from 73 centers in the U. S., Canada, Australia, and Europe. Eligible participants had a viral load of at least 10,000 copies/ml and a CD4 count of at least 100 cells/mm³. Approximately one third of the patients had a baseline viral load of more than 100,000 copies/ml. At enrollment, participants were randomized to receive AZT/3TC (Combivir®) twice daily plus either abacavir 300 mg twice daily or indinavir 800 mg every 8 hours. Matching placebos of both abacavir tablets and indinavir capsules (200 mg) were used, making for a total pill burden of 16 tablets daily. In addition, the dietary restrictions and water requirements for indinavir were relayed to all study participants.

According to the primary endpoint -- proportion of patients with viral load less than 400 copies/ml at week 48 -- there was no difference between the 2 groups, with 51% of both arms achieving this level by intent-to-treat analysis. However, when the analysis was restricted to patients with a baseline viral load of more than 100,000 copies/ml and a more sensitive HIV RNA assay was employed, the proportion of patients with viral loads less than 50 copies/ml was significantly greater in the indinavir group than in the abacavir group (45% vs. 31%, respectively). No differences between the 2 groups were seen in CD4-cell count response or discontinuations for drug-related adverse events. One patient died of a hypersensitivity reaction attributed to abacavir when the patient was mistakenly rechallenged with the drug 3 weeks after starting the study.

These results suggest that, although abacavir may be comparable to indinavir for patients with low viral loads, its efficacy is somewhat decreased for patients above the 100,000 copies/ml threshold. The authors note that the performance of the abacavir arm may have been hampered by the high pill burden and dietary and water requirements of receiving indinavir placebo. Indeed, in preliminary reports from randomized, open-label studies, researchers have shown equivalent results across all viral-load strata when abacavir was compared with indinavir or nelfinavir. An accompanying editorial reviews the science and ethics of studies such as this one that are designed to demonstrate equivalence.

— Paul E. Sax

Published in AIDS Clinical Care May 1, 2001

Citation(s):

Staszewski S et al. Abacavir-lamivudine-zidovudine vs. indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults. JAMA 2001 March 7; 285:1155-63.

• Original article (Subscription may be required)
• Medline abstract (Free)

Djulbegovic B and Clarke M. Scientific and ethical issues in equivalence trials. JAMA 2001 March 7; 285:1206-8.

• Original article (Subscription may be required)
• Medline abstract (Free)