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ICAAC 2013: Single-tablet Regimen Improves ART Adherence and Reduces Hospitalization

Antiretroviral treatment that requires only a single tablet taken once-daily were associated with better viral suppression, higher adherence, and lower likelihood of hospitalization, researchers reported at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013) this month in Denver.

Modern antiretroviral therapy (ART) regimens are much better tolerated and more convenient than early combinations that sometimes required handfuls of pills taken multiple times a day. It is well known that taking ART as directed most of the time leads to better viral suppression, and studies generally find that lower pill burden is associated with better adherence. But it is less clear whether taking 1 instead of 2 pills at a time, or taking them once or twice daily, has a significant effect on treatment adherence and outcomes.

Scott Sutton and colleagues from the Dorn Veterans Administration Medical Center and the University of South Carolina compared viral suppression, medication adherence, and hospitalization among U.S. veterans taking single-tablet or multiple-tablet ART regimens.

This retrospective observational analysis used computerized medical and pharmacy records from 15,602 patients who received HIV medications through the Veterans Administration healthcare system between January 2006 and July 2012. Almost all were men, nearly half were black, more than 40% were white, and the average age was 52 years. About two-thirds were diagnosed with mental health conditions and 40% with drug or alcohol use disorders.

Participants were categorized in the single-tablet regimen group if they ever received a 1-pill-once-daily regimen at any time during the study period (6,191 patients; 40%); others were put in the multiple-tablet regimen group (9,411 patients; 60%). Follow-up lasted at least 2 months without any switches after starting a new regimen.

At baseline, people in the single-tablet and multiple-tablet groups had similar CD4 T-cell counts (mean 432 cells/mm³). However, patients prescribed a single-tablet regimen were less likely to have undetectable viral load at baseline (42% vs 46%) and more likely to be treatment-naive (28% vs 13%).

Almost everyone in the single-tablet regimengroup used Atripla (efavirenz/tenofovir/emtricitabine), a recommended regimen in U.S. and European treatment guidelines. The other available 1-pill regimen, Complera (rilpivirine/tenofovir/emtricitabine) and Stribild (elvitegravir/cobicistat/tenofovir/emtricitabine), were approved more recently in the U.S. (August 2011 and August 2012, respectively). All single-tablet coformulations are marketed by Gilead Sciences, which provided support for the study.

Atripla and Complera include a NNRTI while Stribild includes an HIV integrase inhibitor. There are currently no protease inhibitor-based single-tablet regimens. More than two-thirds of participants in the multiple-tablet group took protease inhibitors.

Results

• Treatment response rates were high overall in both groups, but people taking a single-tablet regimenwere significantly more likely than those on multiple-tablet regimens to achieve undetectable viral load during follow-up (64% vs 60%, respectively).
• A significantly greater proportion of people in the single-tablet group achieved at least 95% adherence (75% vs 56%) and at least 80% adherence (90% vs 78%), as determined by pharmacy claims data (medication possession ratio).
• People taking a single-tablet regimen were significantly less likely to have been hospitalized during follow-up compared with multiple-tablet recipients (27% vs 31%).
• Single-tablet recipients also took longer to be hospitalized and had fewer hospital stays (2.2 vs 2.7, respectively).
• In a multivariate analysis controlling for other factors, people taking single-tablet regimen:

o   Were twice as likely to be at least 95% adherent to treatment (odds ratio 1.98);

o   Were 31% less likely to be hospitalized (hazard ratio 0.69);

o   Had 45% fewer hospitalizations (incidence rate ratio 0.56).

"Patients on [single-tablet regimens] had better adherence compared to those on [multiple-tablet regimens]" and had "reduced risk of hospitalizations, fewer hospitalizations, and longer time to hospitalization," the investigators concluded.

After Suttons' presentation, session moderator Pablo Tebas and others suggested that the results may be affected by "channeling bias." This could include preferentially prescribing boosted protease inhibitors for people with higher baseline viral load or those judged less likely to be adherent, as these drugs are generally more "forgiving" of missed doses. Another example would be patients with pre-existing kidney disease -- a group more likely to be hospitalized -- not being put on tenofovir, which is included in all available single-tablet regimens.

"Healthcare providers and payers may see a benefit in improved medication-taking behavior with ART using a single tablet compared to multiple tablets based on fewer hospital visits and other improvements in clinical outcomes," the researchers suggested in a press release issued by ICAAC. "These clinical outcomes could potentially decrease total healthcare costs in HIV patients."

This suggestion is supported by other studies of U.S. Medicaid participants and individuals with private insurance, which likewise found that people taking single-tablet regimens had fewer hospitalizations than those taking multiple pills. Another benefit in the U.S. is that single-tablet regimens require only 1 prescription co-pay.

9/23/13

Reference

GA Rao, SS Sutton, J Hardin, et al. Impact of highly active antiretroviral therapy regimen on adherence and risk of hospitalization in veterans with HIV/AIDS. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013). Denver, September 10-13, 2013. Abstract H-1464.

Other Source

ICAAC/American Society for Microbiology. Effects on compliance and risk of hospitalization in veterans with HIV/AIDS taking single tablet vs. multiple tablets. Media advisory. September 12, 2013.