High levels of adherence do not prevent accumulation of HIV drug resistance mutations

TLDR

The study evaluates how antiretroviral drug resistance develops in relation to adherence, treatment duration, virologic suppression, and the rate of new resistance mutations across different adherence levels. In a prospective cohort of HIV‑positive urban poor individuals, adherence was measured by unannounced pill counts and two genotypic resistance tests (G1 and G2) were performed six months apart in patients on stable regimens with detectable viremia. High adherence correlates with longer treatment duration and viral suppression, yet among viremic patients it is linked to increased accumulation of new drug resistance mutations, with 23 % of all resistance arising in the highest adherence quintile and over 50 % in the top two quintiles, indicating that exceptionally high adherence does not prevent population‑level drug resistance.

Abstract

To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence.Adherence was measured with unannounced pill counts performed at the participant's usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2.High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92-100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79-100%).Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance.