Differential Impact of Adherence on Long-term Treatment Response Among Naive HIV-infected Individuals

Objectives: To examine the long-term impact of adherence on virologic, immunologic, and dual response stratified by type of HAART regimen in treatment-naive patients starting HAART in British Columbia, Canada; and to assess the degree of virologic and immunologic response associated with emergence of drug resistance, progression to AIDS, and mortality.

Methods: Eligible participants initiated HAART between 1 January 2000 and 30 November 2004, were followed until 30 November 2005, and had at least 2 years of follow-up. Virologic and immunologic responses were dichotomized at their median values. Virologic response was defined as at least 65% of follow-up time with plasma viral load (pVL) of less than 50 copies/ml. Immunologic response was defined as a CD4 cell count increase of at least 145 cells/microl. Adherence measures were based on prescription refill compliance. Proportional odds models and logistic regression were used to address our objectives.

Results: The distribution of patient responses was 394 (44.9%) for CD4+/pVL+ (best), 350 (39.9%) for CD4-/pVL+ or CD4+/pVL- (incomplete), and 134 (15.3%) for CD4-/pVL- (worst). We found a positive correlation between adherence and virologic and immunologic responses (P < 0.01). Having worst compared with best response (reference group) was associated with higher odds of mortality (odds ratio: 6.09; 95% confidence interval: 2.57-14.42) and emergence of drug resistance (odds ratio: 10.56; 95% confidence interval: 5.93-18.81) even after adjusting for adherence and HAART regimen.

Conclusion: Patients not attaining the best virologic and immunologic responses are at a high risk for emergence of drug resistance and mortality, and these responses are highly dependent on the adherence level and initial HAART regimen. Patients on protease inhibitor-single did worse no matter the adherence level.