TY - JOUR

T1 - Heavy antiretroviral exposure and exhausted/limited antiretroviral options

T2 - Predictors and clinical outcomes

AU - Mocroft, Amanda

AU - Pelchen-Matthews, Annegret

AU - Hoy, Jennifer

AU - Llibre, Josep M.

AU - Neesgaard, Bastian

AU - Jaschinski, Nadine

AU - Domingo, Pere

AU - Rasmussen, Line Dahlerup

AU - Günthard, Huldrych F.

AU - Surial, Bernard

AU - Öllinger, Angela

AU - Knappik, Michael

AU - De Wit, Stephane

AU - Wit, Ferdinand

AU - Mussini, Cristina

AU - Vehreschild, Joerg

AU - Monforte, Antonella D.Arminio

AU - Sonnerborg, Anders

AU - Castagna, Antonella

AU - Anne, Alain Volny

AU - Vannappagari, Vani

AU - Cohen, Cal

AU - Greaves, Wayne

AU - Wasmuth, Jan C.

AU - Spagnuolo, Vincenzo

AU - Ryom, Lene

AU - RESPOND Cohort Collaboration

N1 - Publisher Copyright: © 2024 Lippincott Williams and Wilkins. All rights reserved.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - clinical events

KW - heavily treatment experienced

KW - limited treatment options

U2 - 10.1097/QAD.0000000000003798

DO - 10.1097/QAD.0000000000003798

M3 - Journal article

C2 - 38079588

AN - SCOPUS:85186492663

VL - 38

SP - 497

EP - 508

JO - AIDS

JF - AIDS

SN - 1350-2840

IS - 4

ER -