Background: Multi-drug antiretroviral (ARV) resistance in heavily treatment-experienced (HTxE) persons with HIV (PWH) results in limited treatment options. We evaluated the prevalence of HTxE among PWH in the modern antiretroviral treatment (ART) era.
Methods: All ART-experienced adult PWH in care between 2000-2017 at 7 U.S. sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort were included. We computed the annual prevalence of HTxE in PWH defined as having ≤2 available classes with ≤2 active drugs per class based on genotypic mutation data interpreted using the Stanford HIV Drug Resistance Database. For each individual, mutations were carried forward to assess cumulative ARV resistance. Cox proportional hazards models were used to examine the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of HTxE by 3-year calendar periods, adjusting for sex, age, race/ethnicity, site, ART-naive at CNICS entry, prior single/dual NRTI treatment, baseline nadir CD4 and maximum viral load.
Results: Among 26,495 ART-experienced PWH, resistance testing was performed in 8,723 persons with 900 PWH classified as HTxE, the majority of whom were male (85%), white (51%), men who have sex with men (54%), with median age 50 years and nadir CD4 72 cells/mm3. Prevalence of HTxE was 5.2-7.4% in 2000-06, decreasing significantly to 1.8% in 2007, and remained < 1% from 2012-17 (Figure 1). After accounting for population differences, participants entering care in 2012-14 had an 80% lower risk of HTxE compared with those entering in 2006-08 (aHR 0.20, 95% CI 0.09-0.45; p< 0.001).
Conclusions: HTxE prevalence defined by ARV resistance was stable early in the modern ART era (2000-06), dramatically decreased after 2006-08, and has remained < 1% in the contemporary ART era (2012-17), suggesting the decrease is due to the availability of more potent ARVs with a higher barrier to resistance. Other definitions of HTxE are being explored.

Figure 1. Annual prevalence of heavily treatment-experienced persons with HIV, 2000 ? 2017.
[Figure 1. Annual prevalence of heavily treatment-experienced persons with HIV, 2000 ? 2017.]

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