Abstract
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.
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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | AIDS |
Vol/bind | 38 |
Udgave nummer | 4 |
Sider (fra-til) | 497-508 |
Antal sider | 12 |
ISSN | 0269-9370 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:Funding: The International Cohort Consortium of Infectious Disease (RESPOND) has received funding from ViiV Healthcare LLC, Gilead Sciences and Merck Sharp & Dohme. Additional support has been provided by participating cohorts contributing data in-kind and/or statistical support: Austrian HIV Cohort Study (AHIVCOS), The Australian HIV Observational Database (AHOD), CHU Saint-Pierre, University Hospital Cologne, EuroSIDA, Frankfurt HIV Cohort Study, Georgian National AIDS Health Information System (AIDS HIS), Modena HIV Cohort, San Raffaele Scientific Institute, Swiss HIV Cohort Study (SHCS), AIDS Therapy Evaluation in the Netherlands Cohort (ATHENA), Royal Free HIV Cohort Study. AHOD is further supported by grant No. U01-AI069907 from the U.S. National Institutes of Health, and GNT1050874 of the National Health and Medical Research Council, Australia.
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