Heavy antiretroviral exposure and exhausted/limited antiretroviral options: Predictors and clinical outcomes

Amanda Mocroft*, Annegret Pelchen-Matthews, Jennifer Hoy, Josep M. Llibre, Bastian Neesgaard, Nadine Jaschinski, Pere Domingo, Line Dahlerup Rasmussen, Huldrych F. Günthard, Bernard Surial, Angela Öllinger, Michael Knappik, Stephane De Wit, Ferdinand Wit, Cristina Mussini, Joerg Vehreschild, Antonella D.Arminio Monforte, Anders Sonnerborg, Antonella Castagna, Alain Volny AnneVani Vannappagari, Cal Cohen, Wayne Greaves, Jan C. Wasmuth, Vincenzo Spagnuolo, Lene Ryom, RESPOND Cohort Collaboration

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


Objectives:People with HIV and extensive antiretroviral exposure may have limited/exhausted treatment options (LExTO) due to resistance, comorbidities, or antiretroviral-related toxicity. Predictors of LExTO were investigated in the RESPOND cohort.Methods:Participants on ART for at least 5 years were defined as having LExTO when switched to at least two anchor agents and one third antiretroviral (any class), a two-drug regimen of two anchor agents (excluding rilpivirine with dolutegravir/cabotegravir), or at least three nucleoside reverse transcriptase inhibitors. Baseline was the latest of January 1, 2012, cohort enrolment or 5 years after starting antiretrovirals. Poisson regression modeled LExTO rates and clinical events (all-cause mortality, non-AIDS malignancy, cardiovascular disease [CVD], and chronic kidney disease [CKD]).Results:Of 23 827 participants, 2164 progressed to LExTO (9.1%) during 130 061 person-years follow-up (PYFU); incidence 1.66/100 PYFU (95% CI 1.59-1.73). Predictors of LExTO were HIV duration more than 15 years (vs. 7.5-15; adjusted incidence rate ratio [aIRR] 1.32; 95% CI 1.19-1.46), development of CKD (1.84; 1.59-2.13), CVD (1.64; 1.38-1.94), AIDS (1.18; 1.07-1.30), and current CD4+cell count of 350 cells/μl or less (vs. 351-500 cells/μl, 1.51; 1.32-1.74). Those followed between 2018 and 2021 had lower rates of LExTO (vs. 2015-2017; 0.52; 0.47-0.59), as did those with baseline viral load of 200 cp/ml or less (0.46; 0.40-0.53) and individuals under 40. Development of LExTO was not significantly associated with clinical events after adjustment for age and current CD4, except CKD (1.74; 1.48-2.05).Conclusion:Despite an aging and increasingly comorbid population, we found declining LExTO rates by 2018-2021, reflecting recent developments in contemporary ART options and clinical management. Reassuringly, LExTO was not associated with a significantly increased incidence of serious clinical events apart from CKD.

Original languageEnglish
Issue number4
Pages (from-to)497-508
Publication statusPublished - 15. Mar 2024


  • clinical events
  • heavily treatment experienced
  • limited treatment options


Dive into the research topics of 'Heavy antiretroviral exposure and exhausted/limited antiretroviral options: Predictors and clinical outcomes'. Together they form a unique fingerprint.

Cite this