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Association between adherence to antiretroviral therapy and human immunodeficiency virus drug resistance.
Sethi AK, Celentano DD, Gange SJ, Moore RD, Gallant JE.
Clin Infect Dis
2003 Oct 15;37(8):1112-8.
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PubMed entry
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Reviewed by
Susa Coffey, MD
Summary
This prospective study followed 195 subjects treated with antiretroviral therapy (ART) in an urban clinic. At study entry they had HIV viral loads <500 copies/mL, no history of virologic failure, and no known resistance mutations. Adherence was measured at each clinic visit by self-report of doses taken over the previous 3 days. Viral loads were measured at each visit, and genotypes were performed if the viral load was >1,000 copies/mL. At 1 year, 14% of the cohort had developed virologic failure with clinically significant resistance (defined as intermediate or high-level resistance), 66% had no new resistance, and 19% had incomplete follow-up. In multivariate analysis,
development of virologic failure with resistance was strongly associated with high cumulative adherence rates
. The highest rates of resistance were seen at adherence levels of 70-89% (compared with adherence of >90% or <70%). New virologic rebound with resistance was also seen in those who reported adherence rates of 90-99% (13.6 events per 100 person-years) and even in those who reported 100% adherence (9.6 events per 100 person-years). No significant resistance was seen in those with adherence rates <60%. Other risk factors for virologic failure with resistance were nadir CD4 <200 cells/mm3 before ART, and missed clinic visits. Mutations associated with resistance to nucleoside analogues and nonnucleoside reverse transcriptase inhibitors occurred most frequently.
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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