The relationship between resistance and adherence in drug-naive individuals initiating HAART is specific to individual drug classes.
OBJECTIVE
To investigate the relationship between HIV-1 drug resistance and adherence and the accumulation rate of resistance mutations in 1191 HIV-infected, antiretroviral-naive adults initiating highly active antiretroviral therapy in British Columbia, Canada.


METHODS
Plasma samples with plasma viral load >1,000 copies per milliliter collected within 30 months of follow-up were genotyped for drug resistance. Adherence was estimated using prescription refills and plasma drug levels. The primary outcome measure was time to detection of drug resistance. Cox proportional hazard regression was used to calculate hazard ratios (HRs) associated with baseline variables.


RESULTS
The accumulation rates of multiple primary and secondary mutations were similar in patients initiating highly active antiretroviral therapy with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor (NNRTI). Rates decreased approximately 50% per additional mutation. At 80%-90% adherence based on refills, there was greater risk of detecting lamivudine (3TC) [HR 3.0, 95% confidence interval (CI): 1.9 to 4.7; P < 0.0001] and NNRTI mutations (HR 6.0, 95% CI: 3.3 to 10.9; P < 0.0001) compared with the >or=95% refill reference group. In a multivariate model, individuals with <95% refills and consistently detectable plasma drug levels were at increased risk for 3TC (HR 4.5, 95% CI: 2.6 to 7.9; P = 0.0001) and NNRTI resistance (HR 7.0, 95% CI: 3.4 to 14.5; P = 0.0001) compared with the reference group of >or=95% refills with consistently detectable drug levels. Adherence-resistance relationships were much weaker for protease inhibitors and nucleoside reverse transcriptase inhibitors as there was little variance in HRs among the different adherence strata compared with 3TC and NNRTIs.


CONCLUSIONS
The relationships between resistance, adherence, and mutation accumulation differ between HIV drug classes.
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Vancouver, Canada.
Lily W Y
LW
Tam
Celia K S
CK
Chui
Chanson J
CJ
Brumme
David R
DR
Bangsberg
Julio S G
JS
Montaner
Robert S
RS
Hogg
P Richard
PR
Harrigan
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000145:classification; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005260:Female; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D055118:Medication Adherence; D009154:Mutation; D016016:Proportional Hazards Models
D019380:Anti-HIV Agents