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, Stephan
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 - Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2024/3/15
Y1 - 2024/3/15
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 - Anti-HIV Agents/therapeutic use
KW - Anti-Retroviral Agents/therapeutic use
KW - CD4 Lymphocyte Count
KW - Cardiovascular Diseases/chemically induced
KW - HIV Infections/complications
KW - Humans
KW - Renal Insufficiency, Chronic/epidemiology
KW - Viral Load
KW - limited treatment options
KW - clinical events
KW - heavily treatment experienced
UR - http://www.scopus.com/inward/record.url?scp=85186492663&partnerID=8YFLogxK
U2 - 10.1097/QAD.0000000000003798
DO - 10.1097/QAD.0000000000003798
M3 - Journal article
C2 - 38079588
SN - 0269-9370
VL - 38
SP - 497
EP - 508
JO - AIDS
JF - AIDS
IS - 4
ER -