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An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1
BACKGROUND: The long-term efficacy and safety of the 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) and 3-drug single-tablet regimens recommended for antiretroviral therapy (ART)-naive people with HIV-1 (PWH) have yet to be compared directly in clinical trials. This indirect treatment comparis...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031916/ https://www.ncbi.nlm.nih.gov/pubmed/36949442 http://dx.doi.org/10.1186/s12981-023-00507-1 |
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author | Evitt, Lee A. Nanji, Sakina Grove, Richard A. Okoli, Chinyere van Wyk, Jean Snedecor, Sonya J. |
author_facet | Evitt, Lee A. Nanji, Sakina Grove, Richard A. Okoli, Chinyere van Wyk, Jean Snedecor, Sonya J. |
author_sort | Evitt, Lee A. |
collection | PubMed |
description | BACKGROUND: The long-term efficacy and safety of the 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) and 3-drug single-tablet regimens recommended for antiretroviral therapy (ART)-naive people with HIV-1 (PWH) have yet to be compared directly in clinical trials. This indirect treatment comparison (ITC) was conducted to compare the durability of efficacy and long-term safety of DTG + 3TC vs second-generation, integrase strand transfer inhibitor (INSTI)-based, 3-drug, single-tablet regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and DTG/abacavir/3TC (DTG/ABC/3TC) at Week 144 after treatment initiation. METHODS: A systematic literature review identified 4 trials evaluating the treatment regimens of interest in ART-naive PWH (GEMINI-1, GEMINI-2, GS-US-380-1489, and GS-US-380-1490). Safety, efficacy, and tolerability results were compared using fixed-effects Bucher ITC methodology to calculate relative outcomes. RESULTS: Rates of virologic suppression (HIV-1 RNA < 50 copies/mL, US Food and Drug Administration Snapshot analysis) and virologic failure (HIV-1 RNA ≥ 50 copies/mL) as well as mean change in CD4 + cell count were similar with DTG + 3TC, BIC/FTC/TAF, and DTG/ABC/3TC at Week 144. Serious adverse events occurred less frequently with DTG + 3TC compared with both BIC/FTC/TAF (odds ratio [OR], 0.51; 95% CI 0.29–0.87; P = 0.014) and DTG/ABC/3TC (OR, 0.38; 95% CI 0.19–0.75; P = 0.006). Discontinuations and overall adverse events were similar across all 3 regimens. CONCLUSIONS: These results suggest that the 2-drug regimen DTG + 3TC offers comparable and durable efficacy with fewer serious adverse events vs BIC/FTC/TAF and DTG/ABC/3TC through 144 weeks of treatment in ART-naive PWH. These long-term comparative data support the therapeutic value of DTG + 3TC for PWH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12981-023-00507-1. |
format | Online Article Text |
id | pubmed-10031916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100319162023-03-23 An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1 Evitt, Lee A. Nanji, Sakina Grove, Richard A. Okoli, Chinyere van Wyk, Jean Snedecor, Sonya J. AIDS Res Ther Brief Report BACKGROUND: The long-term efficacy and safety of the 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) and 3-drug single-tablet regimens recommended for antiretroviral therapy (ART)-naive people with HIV-1 (PWH) have yet to be compared directly in clinical trials. This indirect treatment comparison (ITC) was conducted to compare the durability of efficacy and long-term safety of DTG + 3TC vs second-generation, integrase strand transfer inhibitor (INSTI)-based, 3-drug, single-tablet regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and DTG/abacavir/3TC (DTG/ABC/3TC) at Week 144 after treatment initiation. METHODS: A systematic literature review identified 4 trials evaluating the treatment regimens of interest in ART-naive PWH (GEMINI-1, GEMINI-2, GS-US-380-1489, and GS-US-380-1490). Safety, efficacy, and tolerability results were compared using fixed-effects Bucher ITC methodology to calculate relative outcomes. RESULTS: Rates of virologic suppression (HIV-1 RNA < 50 copies/mL, US Food and Drug Administration Snapshot analysis) and virologic failure (HIV-1 RNA ≥ 50 copies/mL) as well as mean change in CD4 + cell count were similar with DTG + 3TC, BIC/FTC/TAF, and DTG/ABC/3TC at Week 144. Serious adverse events occurred less frequently with DTG + 3TC compared with both BIC/FTC/TAF (odds ratio [OR], 0.51; 95% CI 0.29–0.87; P = 0.014) and DTG/ABC/3TC (OR, 0.38; 95% CI 0.19–0.75; P = 0.006). Discontinuations and overall adverse events were similar across all 3 regimens. CONCLUSIONS: These results suggest that the 2-drug regimen DTG + 3TC offers comparable and durable efficacy with fewer serious adverse events vs BIC/FTC/TAF and DTG/ABC/3TC through 144 weeks of treatment in ART-naive PWH. These long-term comparative data support the therapeutic value of DTG + 3TC for PWH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12981-023-00507-1. BioMed Central 2023-03-22 /pmc/articles/PMC10031916/ /pubmed/36949442 http://dx.doi.org/10.1186/s12981-023-00507-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Brief Report Evitt, Lee A. Nanji, Sakina Grove, Richard A. Okoli, Chinyere van Wyk, Jean Snedecor, Sonya J. An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1 |
title | An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1 |
title_full | An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1 |
title_fullStr | An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1 |
title_full_unstemmed | An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1 |
title_short | An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1 |
title_sort | indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with hiv-1 |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031916/ https://www.ncbi.nlm.nih.gov/pubmed/36949442 http://dx.doi.org/10.1186/s12981-023-00507-1 |
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