Abstract: Objectives: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited.
Methods: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/μL or a 33% increase where the baseline CD4 count was ≥ 500 cells/μL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint.
Results: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/μL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40-50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/μL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05).
Conclusions: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.
(© 2020 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)
References: Clotet B, Feinberg J, Van Lunzen J et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet 2014; 383 (9936): 2222-2231.
Dejesus E, Rockstroh JK, Henry K et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet 2012; 379 (9835): 2429-2438.
Messiaen P, Wensing AM, Fun A, Nijhuis M, Brusselaers N, Vandekerckhove L. Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis. PLoS One 2013; 8 (1): e52562.
Molina JM, Clotet B, Van Lunzen J et al. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV 2015; 2 (4): e127-e136.
Raffi F, Jaeger H, Quiros-Roldan E et al. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis 2013; 13 (11): 927-935.
Sax PE, Dejesus E, Mills A et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet 2012; 379 (9835): 2439-2448.
Walmsley SL, Antela A, Clumeck N et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med 2013; 369 (19): 1807-1818.
Raffi F, Rachlis A, Stellbrink HJ et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 2013; 381 (9868): 735-743.
Jacobson K, Ogbuagu O. Integrase inhibitor-based regimens result in more rapid virologic suppression rates among treatment-naive human immunodeficiency virus-infected patients compared to non-nucleoside and protease inhibitor-based regimens in a real-world clinical setting: a retrospective cohort study. Medicine (Baltimore) 2018; 97 (43): e13016.
Di Biagio A, Rusconi S, Marzocchetti A et al. The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy. J Med Virol 2014; 86 (10): 1648-1655.
Neesgaard B. Virologic and immunlogic outcomes of integrase inhibitors (INSTIs) in RESPOND. Poster 504. In: CROI Conference on Retroviruses and Opportunistic Infections; 2019; 2019.
The RESPOND study group. Uptake and discontinuation of integrase inhibitors (INSTIs) in a large cohort setting. In: 2019.
Kowalska JD, Friis-Moller N, Kirk O et al. The Coding Causes of Death in HIV (CoDe) Project: initial results and evaluation of methodology. Epidemiology 2011; 22 (4): 516-523.
Mocroft A, Furrer HJ, Miro JM et al. The incidence of AIDS-defining illnesses at a current CD4 count >/= 200 cells/muL in the post-combination antiretroviral therapy era. Clin Infect Dis 2013; 57 (7): 1038-1047.
Snedecor SJ, Radford M, Kratochvil D, Grove R, Punekar YS. Comparative efficacy and safety of dolutegravir relative to common core agents in treatment-naive patients infected with HIV-1: a systematic review and network meta-analysis. BMC Infect Dis 2019; 19 (1): 484.
Yang LL, Li Q, Zhou LB, Chen SQ. Meta-analysis and systematic review of the efficacy and resistance for human immunodeficiency virus type 1 integrase strand transfer inhibitors. Int J Antimicrob Agents 2019; 54 (5): 547-555.
Aboud M, Kaplan R, Lombaard J et al. Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. Lancet Infect Dis 2019; 19 (3): 253-264.
Meireles MV, Pascom ARP, Duarte EC. Factors associated with early virological response in HIV-infected individuals starting antiretroviral therapy in Brazil (2014-2015): Results from a large HIV surveillance cohort. AIDS 2018; 78(4):e19-e27.
Meireles MV, Pascom ARP, Duarte EC, McFarland W. Comparative effectiveness of first-line antiretroviral therapy: results from a large real-world cohort after the implementation of dolutegravir. AIDS 2019; 33(10):1663-1668.
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