The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time.
OBJECTIVE
To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens.


METHODS
Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N = 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective.


RESULTS
The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value <0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and boosted protease inhibitor-based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality.


CONCLUSIONS
Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.
Lima
Viviane D
VD
British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, 608-1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada. vlima@cfenet.ubc.ca
Harrigan
Richard
R
Bangsberg
David R
DR
Hogg
Robert S
RS
Gross
Robert
R
Yip
Benita
B
Montaner
Julio S G
JS
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D013997:Time Factors
D019380:Anti-HIV Agents