The risk of virologic failure decreases with duration of HIV suppression, at greater than 50% adherence to antiretroviral therapy

• Published in: PloS one 2009-09, Vol.4 (9), p.e7196-e7196
• Main Authors: Rosenblum, Michael, Deeks, Steven G, van der Laan, Mark, Bangsberg, David R
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adhesion; Adult; Adults; AIDS; Anti-HIV Agents - pharmacology; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Biological products industry; CD4 antigen; CD4-Positive T-Lymphocytes - metabolism; Cohort Studies; DNA polymerases; Failure; Female; Highly active antiretroviral therapy; HIV; HIV Infections - drug therapy; HIV patients; Human immunodeficiency virus; Humans; Infectious Diseases; Infectious Diseases/HIV Infection and AIDS; Likelihood Functions; Lymphocytes T; Male; Mathematics/Statistics; Maximum likelihood estimation; Middle Aged; Models, Statistical; Mortality; Patient Compliance; Protease; Protease inhibitors; Protease Inhibitors - pharmacology; Proteases; Risk; Ritonavir; RNA-directed DNA polymerase; Statistical analysis; Structural models; T cells; Therapy; Treatment Outcome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007196

We hypothesized that the percent adherence to antiretroviral therapy necessary to maintain HIV suppression would decrease with longer duration of viral suppression. Eligible participants were identified from the REACH cohort of marginally housed HIV infected adults in San Francisco. Adherence to antiretroviral therapy was measured through pill counts obtained at unannounced visits by research staff to each participant's usual place of residence. Marginal structural models and targeted maximum likelihood estimation methodologies were used to determine the effect of adherence to antiretroviral therapy on the probability of virologic failure during early and late viral suppression. A total of 221 subjects were studied (median age 44.1 years; median CD4+ T cell nadir 206 cells/mm(3)). Most subjects were taking the following types of antiretroviral regimens: non-nucleoside reverse transcriptase inhibitor based (37%), ritonavir boosted protease inhibitor based (28%), or unboosted protease inhibitor based (25%). Comparing the probability of failure just after achieving suppression vs. after 12 consecutive months of suppression, there was a statistically significant decrease in the probability of virologic failure for each range of adherence proportions we considered, as long as adherence was greater than 50%. The estimated risk difference, comparing the probability of virologic failure after 1 month vs. after 12 months of continuous viral suppression was 0.47 (95% CI 0.23-0.63) at 50-74% adherence, 0.29 (CI 0.03-0.50) at 75-89% adherence, and 0.36 (CI 0.23-0.48) at 90-100% adherence. The risk of virologic failure for adherence greater than 50% declines with longer duration of continuous suppression. While high adherence is required to maximize the probability of durable viral suppression, the range of adherence capable of sustaining viral suppression is wider after prolonged periods of viral suppression.