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High levels of adherence do not prevent accumulation of HIV drug resistance mutations.
Bangsberg DR, Charlebois ED, Grant RM, Holodniy M, Deeks SG, Perry S, Conroy KN, Clark R, Guzman D, Zolopa A, Moss A.
AIDS
2003 Sep 5;17(13):1925-32.
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PubMed entry
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Reviewed by
Susa Coffey, MD
Summary
In this prospective cohort study, also in an urban poor population, 148 individuals on stable ART (with three or more antiretroviral medications) were assessed for adherence by unannounced pill counts every 3-6 weeks. To identify the development of new drug resistance mutations, a subset of 57 subjects on stable ART with incomplete viral suppression (HIV viral load >50 copies/mL) received genotypes at baseline and at 6 months. These subjects had an average of 3.2 resistance mutations at baseline and developed a mean of 0.93 new primary or secondary mutations by 6 months. The development of new resistance mutations was associated with duration of prior ART and with adherence. The authors estimated the proportion of drug resistance mutations expected over the course of 12 months, by adherence strata, and reported that
23% of resistance mutations would occur in the top quintile of adherence (92-100%), and >50% of resistance mutations in individuals with 79-100% adherence
. In this cohort, new resistance was seen primarily to the protease inhibitor class of medications.
Comment
This and a related study (see below), while different in study populations and methods, both demonstrate a conundrum of antiretroviral therapy. Although high levels of medication adherence are associated with increased rates of viral suppression, and with protection from HIV-associated morbidity and mortality, close (but perhaps imperfect) adherence may also lead to high rates of drug resistance. Low levels of adherence, on the other hand, are not adequate to suppress HIV viremia; neither do they engender drug resistance.
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