Not All Missed Doses Are the Same: Sustained NNRTI Treatment Interruptions Predict HIV Rebound at Low-to-Moderate Adherence Levels

• Published in: PloS one Vol. 3; no. 7; p. e2783
• Main Authors: Parienti, Jean-Jacques, Das-Douglas, Moupali, Massari, Véronique, Guzman, David, Deeks, Steven G., Verdon, Renaud, Bangsberg, David R.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.07.2008; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adhesion; Adult; Adults; AIDS; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiretroviral Therapy, Highly Active; Biological products industry; Case-Control Studies; Clinical trials; Cohort Studies; Confidence intervals; Disease prevention; DNA polymerases; Drug dosages; Drug resistance; Drug therapy; Drugs; Efavirenz; Epidemiology; Female; Health care access; Health risks; Highly active antiretroviral therapy; HIV; HIV - metabolism; HIV Infections - drug therapy; Hospitals; Human immunodeficiency virus; Humans; Infections; Infectious diseases; Infectious Diseases/HIV Infection and AIDS; Interruption; Male; Microelectromechanical systems; Middle Aged; Monitoring systems; Nevirapine; Odds Ratio; Patient Compliance; Plasma; Public Health and Epidemiology/Infectious Diseases; Reverse Transcriptase Inhibitors - pharmacology; Ribonucleic acid; Risk assessment; Risk reduction; RNA; RNA, Viral - metabolism; RNA-directed DNA polymerase; Studies; Therapy; Virology/Antivirals, including Modes of Action and Resistance; San Francisco California; California; France; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0002783

While the relationship between average adherence to HIV potent antiretroviral therapy is well defined, the relationship between patterns of adherence within adherence strata has not been investigated. We examined medication event monitoring system (MEMS) defined adherence patterns and their relation to subsequent virologic rebound. We selected subjects with at least 3-months of previous virologic suppression on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen from two prospective cohorts in France and North America. We assessed the risk of virologic rebound, defined as HIV RNA of >400 copies/mL according to several MEMS adherence measurements. Seventy two subjects were studied, five of them experienced virologic rebound. Subjects with and without virologic rebound had similar baseline characteristics including treatment durations, regimen (efavirenz vs nevirapine), and dosing schedule. Each 10% increase in average adherence decreased the risk of virologic rebound (OR = 0.56; 95% confidence interval (CI) [0.37, 0.81], P<0.002). Each additional consecutive day off therapy for the longest treatment interruption (OR = 1.34; 95%CI [1.15, 1.68], P<0.0001) and each additional treatment interruption for more than 2 days (OR = 1.38; 95%CI [1.13, 1.77], P<0.002) increased the risk of virologic rebound. In those with low-to-moderate adherence (i.e. <80%), treatment interruption duration (16.2 days versus 6.1 days in the control group, P<0.02), but not average adherence (53.1% vs 55.9%, respectively, P = 0.65) was significantly associated with virologic rebound. Sustained treatment interruption may pose a greater risk of virologic rebound on NNRTI therapy than the same number of interspersed missed doses at low-to-moderate adherence.