Susan Swindells, M.B.B.S., of the University of Nebraska Medical Center, Omaha, presented the findings of the study today at a JAMA media briefing at the International AIDS Conference in Toronto.
The long-term adverse effects, expense, and difficulty of sustained adherence to multidrug antiretroviral regimens have prompted studies of simpler therapies for human immunodeficiency virus type 1 (HIV-1) infection. Treatment cessation, intermittent therapy, and induction-maintenance (a few months of triple therapy followed by simplified therapy) regimens have been evaluated with mostly inferior results, according to background information in the article.
Dr. Swindells and colleagues conducted a study to determine whether a simplified maintenance therapy with the antiretroviral medication "boosted" atazanavir alone after virologic suppression (cessation of detectable HIV virus replication) would not markedly increase the risk of virologic failure. Protease inhibitors, such as atazanavir, are often combined with a small dose of ritonavir to increase blood levels -- a phenomenon known as "boosting." This regimen was selected because of low pill burden, once-daily dosing, safety, and unique resistance profile. The 24-week pilot study, conducted between Sept. 2004 and April 2006, included 36 HIV-infected adults with virologic suppression for 48 weeks or longer receiving their first protease inhibitor (PI)--based regimen. Participants switched PIs to atazanavir-ritonavir at entry and discontinued nucleoside analog reverse transcriptase inhibitors (NRTIs) after 6 weeks. Virologic failure was defined as two consecutive HIV-1 RNA measurements of 200 copies/mL or more. The final analysis included 34 patients.
Virologic success (absence of failure) through 24 weeks of simplified therapy occurred in 91 percent of patients (31 of 34). Three participants experienced virologic failure at 12, 14, and 20 weeks after simplification. Resistance testing at failure did not identify protease inhibitor resistance mutations. Atazanavir concentrations in the blood at failure were low or below detection in 2 of 3 participants experiencing failure, indicating these patients may not have taken the prescribed doses. There were no treatment discontinuations for adverse events after simplification and no significant changes in CD4 cell counts.
"In this pilot study, the data suggest that simplified maintenance therapy with atazanavir-ritonavir alone in patients who have never experienced treatment failure may be efficacious in maintaining HIV-1 RNA suppression below 200 copies/mL for 24 weeks after discontinuing NRTIs," the authors write. "Maintenance therapy with a single boosted PI offers a treatment strategy with potentially less complexity, pill burden, long-term complications, and cost."
The researchers add that although the findings are encouraging, caution regarding inferences is warranted due to study limitations such as the small number of participants in the study. "Larger, randomized trials comparing this approach with standard antiretroviral therapy are warranted." (JAMA. 2006;296:806-814. Available pre-embargo to the media at www.jamamedia.org)
This work was supported by NIH grants and a Virology Support Laboratory subcontract of the ACTG Central Group Grant. Industry support from Bristol-Myers Squibb and Abbott Laboratories was in the form of supplying study drugs and participation on the protocol team.
Note: This story has been adapted from a news release issued by JAMA and Archives Journals.