Trends in antiretroviral therapy prescription, durability and modification

Eaton, Ellen; Tamhane, Ashutosh; Davy-Méndez, Thibaut; Mathews, W. Christopher; Moore, Richard D.; Saag, Michael S.; Mugavero, Michael J.

doi:10.1097/qad.0000000000001708

Cited by 30 publications

(21 citation statements)

References 22 publications

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“…Most subjects, especially in the early period, received PI-based cART regimens, which showed a higher risk for first-line modification compared to NNRTI-or INSTI-based regimens. These results are in line with previous studies, showing an inferiority of PI-based regimens compared to NNRTI-or INSTI-based regimens in terms of treatment [22,23]. This might be due to more interactions with other medications and higher rates of side effects.…”

Section: Discussionsupporting

confidence: 92%

Treatment modification after starting cART in people living with HIV: retrospective analysis of the German ClinSurv HIV Cohort 2005–2017

et al. 2020

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Objective Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving. Methods We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data. Results We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR). Conclusions Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.

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Section: Discussionsupporting

confidence: 92%

Treatment modification after starting cART in people living with HIV: retrospective analysis of the German ClinSurv HIV Cohort 2005–2017

et al. 2020

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“…The proportion of discontinuations due to treatment failure was very low overall, which is consistent with the high effectiveness of these newer treatments shown in clinical trials [14]. These findings are consistent with those from a large cohort in the United States, which found very low rates of treatment change associated with virological failure in recent years [15].…”

Section: Resultssupporting

confidence: 85%

Durability of First-Line Antiretroviral Regimens in the era of Integrase Inhibitors: A Cohort of HIV-Positive Individuals in Spain, 2014–2015

et al. 2018

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Background: We compared time to treatment change (TC), viral suppression (VS) and change in CD4 + T-cell counts of first-line antiretroviral regimens (ART). Methods: We analysed HIV treatment-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) initiating the most commonly used ART regimens from September 2014 to November 2015. We used proportional hazards models on the sub-distribution hazard to estimate sub-distribution hazard ratios (sHR) for time to TC, logistic regression to estimate odds ratios (ORs) for VS (viral load <50 copies/ml), and linear regression to assess mean differences in CD4 + T-cell changes from ART initiation. Results: Among 960 individuals, tenofovir (TDF)/emtricitabine (FTC)/rilpivirine (RPV) was the most frequently prescribed regimen (24.2%), followed by elvitegravir (EVG)/cobicistat (COBI)/TDF/FTC (22.8%), abacavir (ABC)/lamivudine (3TC)/dolutegavir (DTG; 17.4%), TDF/ FTC+darunavir/ritonavir (DRV/r) or darunavir/cobicistat (DRV/c; 12.1%), TDF/FTC/efavirenz (EFV; 8.8%), TDF/ FTC+raltegravir (RAL; 7.7%) and TDF/FTC+DTG (7.0%). Initiating ART with TDF/FTC+DRV/r or DRV/c (adjusted sHR: 2.96; 95% CI: 1.44, 6.08), TDF/FTC/EFV (2.18; 0.98, 4.82), TDF/FTC+RAL (2.37; 1.08, 5.22) and TDF/FTC+DTG (6.34; 3.18, 12.64) was associated with a higher risk of TC compared to ABC/3TC/DTG. At 24 weeks, VS was lower in TDF/FTC+DRV/r or DRV/c (adjusted OR: 0.37, 95% CI: 0.18, 0.74) compared with ABC/3TC/DTG, and CD4 + T-cell increase was lower in patients initiating with TDF/FTC/RPV (adjusted mean difference: -75.9, 95% CI: -130.6, -21.2) compared with those who did with ABC/3TC/DTG. Conclusions: Time to TC, VS and change in CD4 + T-cell counts varies by initial regimen. These differences may be useful for making decision when initiating ART.

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“…Various studies have reported that gender, age, transmission mode, treatment period, specific drugs or ART regimen may be major factors for discontinuation of first-line ART regimens [ 2 , 10 , 22 ]. Rates of ART discontinuation were found to be remarkably higher for injection drug users (IDUs) and/or HIV/hepatitis C virus (HCV) co-infected patients compared to other groups in many studies [ 6 , 20 , 26 – 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…ART regimens were defined according to their classes as follows: 2 nucleoside analogue reverse transcriptase inhibitor (NRTI)s + a 3rd agent [non-nucleoside reverse transcriptase inhibitor (NNRTI), boosted protease inhibitor (PI), or integrase strand transfer inhibitor (InSTI), or an InSTI with a PI (InSTI/PI). NNRTI/InSTI and NNRTI/PI-based regimens were categorized as InSTI-based and PI-based, respectively [ 10 ].…”

Section: Methodsmentioning

confidence: 99%

“…Randomized controlled trials with novel regimens mainly containing different InSTIs have demonstrated favourable efficacy, tolerability and ease of use [ 9 ]. However, studies comparing regimens including older drugs with largely InSTI-based contemporary regimens in terms of durability and reasons for discontinuation of the initial regimen are limited with observational cohorts even in resource rich countries and there is little information available from middle income countries [ 10 – 12 ]. Large-scale studies analysing ART modifications comparing regimens including historical versus novel drugs are not available in Turkey.…”

Section: Introductionmentioning

confidence: 99%

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Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011–2017

Korten

Gökengin

Eren³

et al. 2021

AIDS Res Ther

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Background There is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The aim of this study was to evaluate the discontinuation of first ART before and after the availability of better tolerated and less complex regimens by comparing the frequency, reasons and associations with patient characteristics. Methods A total of 3019 ART-naive patients registered in the HIV-TR cohort who started ART between Jan 2011 and Feb 2017 were studied. Only the first modification within the first year of treatment for each patient was included in the analyses. Reasons were classified as listed in the coded form in the web-based database. Cumulative incidences were analysed using competing risk function and factors associated with discontinuation of the ART regimen were examined using Cox proportional hazards models and Fine-Gray competing risk regression models. Results The initial ART regimen was discontinued in 351 out of 3019 eligible patients (11.6%) within the first year. The main reason for discontinuation was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and provider preference (5.4%). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based (aHR = 4.4, [95% CI 3.0–6.4]; p < 0.0001) or protease inhibitor (PI)-based regimens (aHR = 4.3, [95% CI 3.1–6.0]; p < 0.0001) relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017) (aHR = 0.6, [95% CI 0.4–0.9]; p < 0.0001) was less likely to be discontinued. A lower rate of treatment discontinuation for intolerance/toxicity was observed with InSTI-based regimens (2.0%) than with NNRTI- (6.6%) and PI-based regimens (7.5%) (p < 0.001). The percentage of patients who achieved HIV RNA < 200 copies/mL within 12 months of ART initiation was 91% in the ART discontinued group vs. 94% in the continued group (p > 0.05). Conclusion ART discontinuation due to intolerance/toxicity and virologic failure decreased over time. InSTI-based regimens were less likely to be discontinued than PI- and NNRTI-based ART.

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Trends in antiretroviral therapy prescription, durability and modification

Cited by 30 publications

References 22 publications

Treatment modification after starting cART in people living with HIV: retrospective analysis of the German ClinSurv HIV Cohort 2005–2017

Treatment modification after starting cART in people living with HIV: retrospective analysis of the German ClinSurv HIV Cohort 2005–2017

Durability of First-Line Antiretroviral Regimens in the era of Integrase Inhibitors: A Cohort of HIV-Positive Individuals in Spain, 2014–2015

Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011–2017

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