Heavy arv exposure and exhausted/limited arv options: predictors and clinical outcomes.

Mocroft, Amanda; Pelchen-Matthews, Annegret; Hoy, Jennifer; Llibre, Josep M; Neesgaard, Bastian; Jaschinski, Nadine; Domingo, Pere; Rasmussen, Line Dahlerup; Günthard, Huldrych F; Surial, Bernard; Öllinger, Angela; Knappik, Michael; De Wit, Stephan; Wit, Ferdinand; Mussini, Cristina; Vehreschild, Joerg; Monforte, Antonella D'Arminio; Sonnerborg, Anders; Castagna, Antonella; Anne, Alain Volny; ... (2024). Heavy arv exposure and exhausted/limited arv options: predictors and clinical outcomes. AIDS, 38(4), pp. 497-508. Wolters Kluwer Health 10.1097/QAD.0000000000003798

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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.

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