Medscape Medical News 2004. © 2004 Medscape

Yael Waknine

May 27, 2004 — Short-cycle structured intermittent therapy (SIT) with a once-daily regimen of didanosine, lamivudine, and efavirenz maintains suppression of plasma HIV RNA while preserving CD4+ T-cell counts in patients with chronic HIV infection, according to the results of a proof-of-concept study published in the June 1 issue of the Journal of Infectious Diseases.

"Continuous combination antiretroviral therapy (ART) has significantly reduced HIV-associated morbidity and mortality among patients who have access to such therapy," write Mark Dybul, MD, from the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and colleagues. "Unfortunately, long-term continuous ART may not be sustainable for many individuals and nations, because of drug toxicities, difficulty with adherence, and a prohibitive monetary cost."

According to the authors, the once-daily ART regimen administered in seven days on, seven days off cycles ("7-7" approach) involves half as much antiretroviral medication as continuous therapy, thus reducing costs and perhaps drug-related toxicities in the long run. Once-daily administration may enhance compliance as well.

In this study, investigators enrolled eight HIV-infected patients who had been successfully treated with an ART regimen of at least three drugs for a period of more than six months. Patients were treated with a cyclic regimen of seven days without ART followed by seven days of once-daily ART (didanosine 200 mg, lamivudine 300 mg, and efavirenz 600 mg). Patients underwent laboratory evaluations after ART-free periods every four weeks during the first 48 weeks of the study and at least every 12 weeks thereafter.

Seven of eight patients maintained suppression of plasma HIV RNA to undetectable levels (< 50 copies/mL) for 60 to 84 weeks. One patient, withdrawing from the study for personal reasons, had likewise maintained suppression at week 24.

Assays with a limit of detection of less than 50 copies/mL showed no transient increases in plasma viremia ("blips") in any of the study patients. Likewise, use of more sensitive assays with a detection limit of less than 1 copy/mL showed no "blips" for up to 72 weeks in five patients with adequate samples. According to the investigators, the lack of rebound viremia may be a result of the long half-life of the antiretroviral drugs used, as demonstrated by the detection of efavirenz in the plasma of all seven patients at the end of no-therapy periods.

No significant changes were observed in CD4+ or CD8+ T-cell counts, serum hepatic transaminase levels, or serum lipid levels, nor was there evidence of resistance to ART.

The authors note that strict adherence to the regimen is necessary, and that once-daily dosing may increase compliance. "[T]he feasibility of such an approach will require studies of larger numbers of patients for extended periods," they write.

"If the safety and efficacy of short-cycle SIT ultimately are demonstrated in clinical settings, it might prove to be an important strategy to expand therapy in resource-limited settings," the authors point out. "In this regard, randomized, controlled clinical trials are being conducted in various sites in the United States and other countries to evaluate the clinical usefulness of short-cycle SIT."

J Infect Dis. 2004;189(11):1974-1982

Reviewed by Gary D. Vogin, MD

Yael Waknine is a freelance writer for Medscape.