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How Much Adherence Is Enough?

In two new studies, moderate adherence to an NNRTI- or boosted-PI–based regimen often led to sustained virologic suppression.

Multiple studies have shown that adherence is the Achilles’ heel of potent antiretroviral therapy (ART), and many clinicians still firmly believe that near-perfect adherence is necessary for sustained virologic suppression. However, this idea is based on data from nearly a decade ago, when unboosted PIs (which are rarely if ever used for therapy today) were the most potent drugs available. Results from newer studies suggest that NNRTI- and boosted-PI–based regimens may be somewhat more forgiving of missed doses and that patients using these regimens can achieve virologic suppression with more realistic levels of adherence. Two recent investigations address these possibilities.

Nachega and colleagues studied 2821 HIV-infected adults in South Africa who were treated with regimens containing an NNRTI (efavirenz in 65% of patients, nevirapine in 35%). Adherence was determined using pharmacy-pickup records, and sustained virologic suppression was defined as viral loads <400 copies/mL from 1 month after ART initiation until the end of follow-up (median duration, 2.2 years). Rates of sustained virologic suppression were 12.6% for patients who filled fewer than 50% of their prescriptions, 25.2% for those who filled 50% to 59% of their prescriptions, and 71.7% for those who filled 90% to 100% of their prescriptions. Each 10% increase in pharmacy pickups beyond 50% was associated with a mean 10% absolute increase in the proportion of patients who achieved sustained virologic suppression. Significant predictors of shorter time to virologic failure after previous suppression included low CD4-cell counts and high viral load at therapy initiation, use of nevirapine rather than efavirenz, and low therapy adherence.

In a small, industry-sponsored study, Shuter and colleagues evaluated lopinavir/ritonavir use among 64 HIV-infected adults in New York City. The mean adherence rate, assessed by the Medication Event Monitoring System, was 72.8%. At 24 weeks, rates of virologic suppression were similar between patients with high adherence and those with lower levels of adherence; overall, 80% of patients achieved viral loads <400 copies/mL, and 59% achieved viral loads <75 copies/mL.

Comment: Despite their low genetic barrier to resistance, NNRTIs often lead to sustained virologic suppression with only moderate levels of adherence. Similarly, boosted PIs perform quite well with moderate (and sometimes even poor) adherence. No wonder NNRTIs and boosted PIs are currently the preferred drugs for antiretroviral-naive patients who are initiating therapy! The present results notwithstanding, clinicians should continue to advise their patients to strive for maximal medication adherence.

— Carlos del Rio, MD

Published in AIDS Clinical Care July 2, 2007

Citation(s):

Nachega JB et al. Adherence to nonnucleoside reverse transcriptase inhibitor–based HIV therapy and virologic outcomes. Ann Intern Med 2007 Apr 17; 146:564-73.

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

Shuter J et al. HIV-infected patients receiving lopinavir/ritonavir-based antiretroviral therapy achieve high rates of virologic suppression despite adherence rates less than 95%. J Acquir Immune Defic Syndr 2007 May 1; 45:4-8.

• Medline abstract (Free)