OBJECTIVE: Historically, a high burden of resistance to antiretroviral therapy (ART) in heavily treatment-experienced (HTE) persons with HIV (PWH) resulted in limited treatment options (LTOs). We evaluated the prevalence, risk factors, and virologic control of HTE PWH with LTO throughout the modern ART era. DESIGN: We examined all ART-experienced PWH in care between 2000 and 2017 in the Centers for AIDS Research Network of Integrated Clinical Systems cohort. METHODS: We computed the annual prevalence of HTE PWH with LTO defined as having two or less available classes with two or less active drugs per class based on genotypic data and cumulative antiretroviral resistance. We used multivariable Cox proportional hazards models to examine risk of LTO by 3-year study entry periods adjusting for demographic and clinical characteristics. RESULTS: Among 27 133 ART-experienced PWH, 916 were classified as having LTO. The prevalence of PWH with LTO was 5.2-7.5% in 2000-2006, decreased to 1.8% in 2007, and remained less than 1% after 2012. Persons entering the study in 2009-2011 had an 80% lower risk of LTO compared with those entering in 2006-2008 (adjusted hazard ratio 0.20; 95% confidence interval: 0.09-0.42). We found a significant increase in undetectable HIV viral loads among PWH ever classified as having LTO from less than 30% in 2001 to more than 80% in 2011, comparable with persons who never had LTO. CONCLUSION: Results of this large multicenter study show a dramatic decline in the prevalence of PWH with LTO to less than 1% with the availability of more potent drugs and a marked increase in virologic suppression in the current ART era.