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. 2024 Mar 15;38(4):497-508.
doi: 10.1097/QAD.0000000000003798. Epub 2023 Dec 8.

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

Amanda Mocroft  1   2 , Annegret Pelchen-Matthews  2 , Jennifer Hoy  3 , Josep M Llibre  4 , Bastian Neesgaard  1 , Nadine Jaschinski  1 , Pere Domingo  5 , Line Dahlerup Rasmussen  6 , Huldrych F Günthard  7   8 , Bernard Surial  9 , Angela Öllinger  10 , Michael Knappik  11 , Stephane de Wit  12 , Ferdinand Wit  13 , Cristina Mussini  14 , Joerg Vehreschild  15 , Antonella D'Arminio Monforte  16 , Anders Sonnerborg  17 , Antonella Castagna  18 , Alain Volny Anne  19 , Vani Vannappagari  20 , Cal Cohen  21 , Wayne Greaves  22 , Jan C Wasmuth  23 , Vincenzo Spagnuolo  18 , Lene Ryom  1   24   25 ; for the RESPOND cohort collaboration
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Free article

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

Amanda Mocroft et al. AIDS. .
Free article

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.

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References

    1. Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, et al. Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV infection, 2000-2016 . JAMA Netw Open 2020; 3:e207954.
    1. Vizcarra P, Fontecha M, Monsalvo M, Vivancos MJ, Rojo A, Casado JL. Efficacy and safety of dolutegravir plus boosted-darunavir dual therapy among highly treatment-experienced patients . Antivir Ther 2019; 24:467–471.
    1. Kozal M, Aberg J, Pialoux G, Cahn P, Thompson M, Molina JM, et al. Fostemsavir in adults with multidrug-resistant HIV-1 infection . N Engl J Med 2020; 382:1232–1243.
    1. Bajema KL, Nance RM, Delaney JAC, Eaton E, Davy-Mendez T, Karris MY, et al. Substantial decline in heavily treated therapy-experienced persons with HIV with limited antiretroviral treatment options . AIDS 2020; 34:2051–2059.
    1. Costagliola D, Lodwick R, Ledergerber B, Torti C, van Sighem A, Podzamczer D, et al. Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study . Lancet Infect Dis 2012; 12:119–127.

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