Clinical Briefs

Simultaneous or Sequential Therapy for HIV-1?

By Joan Unger, RN, MS, ARNP-C

Experts agree a combination of antiretroviral drugs markedly suppresses human immunodeficiency virus (HIV) replication. The U.S. Department of Health and Human Services recommends a combination of two nucleoside analogue reverse transcriptase inhibitors and a potent protease inhibitor as preferred treatment for HIV infection. The durability of antiretroviral activity and duration of HIV suppression with the combination is unknown. Several reports in late 1997 indicated that 30-60% of patients on a combination regimen did not maintain viral suppression in clinical practice. This led scientists to ask if the problem could result from sequential rather than simultaneous administration of the drugs.

Study Included Three Regimens

This randomized, multicenter double-blind study compared the effects of a three-drug simultaneous regimen with a sequential regimen in patients with HIV.1 Ninety-seven patients were treated with zidovudine for at least six months and had serum HIV RNA levels of at least 20,000 copies/mL and a CD4 cell count 0.05-0.40 x 109/L. Three regimens were initiated:
• indinavir 800 mg every eight hours;
• zidovudine 200 mg every eight hours and lamivudine 150 mg every 12 hours;
• or all three drugs.

After 24 weeks of blind therapy, all patients received open-label three-drug therapy.

At 100 weeks, simultaneous use of indinavir, zidovudine, and lamivudine suppressed HIV RNA to less than 500 copies/mL and increased the median CD4 count to 0.209 x 109/L above baseline in 78% of patients. When the drugs were initiated sequentially, only 30% of patients in the zidovudine-lamivudine group and 45% of those in the indinavir group had a reduction in HIV RNA to < 500 copies/mL and increased median CD4 cell count to 0.101-0.163 x 109/L over baseline at 100 weeks.

The researchers concluded that a three-drug simultaneous regimen has durable antiretroviral activity for at least two years, whereas sequential administration was much less effective.

Reference

1. Gulick R, Meliors J, Havlir D, et al. Simultaneous vs. sequential initiation of therapy with indinavir, zidovudine, and lamivudine for HIV-1 infections. JAMA 1998;280:35-41.