Repeated measures longitudinal analyses of HIV virologic response as a function of percent adherence, dose timing, genotypic sensitivity, and other factors.
BACKGROUND
Adherence to antiretroviral medications is critical to achieving HIV viral suppression. Studies have been limited to cross-sectional analyses using measures that reflect only the percentage of prescribed doses taken (percent adherence), however. The contribution of dose timing and other factors to achieving virologic suppression has received less scrutiny.


METHODS
In a longitudinal study, we collected detailed adherence information using multiple tools along with demographic, clinical, social-behavioral, and virologic measures. Subjects were followed for 48 weeks. Percent adherence, dose-timing, genotypic sensitivity, and virologic outcomes were collected every 4 weeks. Repeated measures mixed effects models (RMMEMs) were used to model the relation between virologic outcomes and adherence as well as genotypic sensitivity and others.


RESULTS
Of the 141 subjects, mean percent adherence was 73% with a downward trend. Viral load (VL) dropped significantly (P = 0.01) over time. RMMEMs revealed that higher genotypic sensitivity, higher percent adherence, lower baseline VL, longer inclusion in the study, earlier HIV stage, and smaller dose-timing error were significantly associated with lower VL. In multivariate modeling, a 0.50 increase in the genotypic sensitivity score, a 10% increase in adherence, and a decrease of 3 hours of dose-timing error were associated with a decrease in log10 HIV RNA at 48 weeks of 0.69, 0.54, and 0.48, respectively (P < 0.05 for each).


CONCLUSIONS
Long-term viral suppression requires consistent and high percent adherence accompanied by optimal interdose intervals. Efforts to improve viral outcomes should address not only missed doses but excessive variation in dose timing and prevention of adherence decline over time. Preventing the development and transmission of resistant variants is also critically important.
Division of General Internal Medicine and Health Services Research, Department of Medicine, University of California-Los Angeles (UCLA), 911 Broxton Plaza, Los Angeles, CA 90095-1736, USA. hhliu@ucla.edu
Honghu
H
Liu
Loren G
LG
Miller
Ron D
RD
Hays
Carol E
CE
Golin
Tongtong
T
Wu
Neil S
NS
Wenger
Andrew H
AH
Kaplan
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood; D013223:Statistics as Topic; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral