Comparative Analysis of the Efficacy and Safety of HIV/AIDS Treatment Strategies: A Comprehensive Review of Clinical Trial Data

Authors

  • Mu Yan The First Clinical Medical College and College of Modern Biomedical Industry, Kunming Medical University, China
  • Yuping Liu School of Public Health, Kunming Medical University, China
  • Jiaying He School of Pharmaceutical Sciences & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, China
  • Siyan Zhou Yunnan Provincial Center for Drug Policy Research, College of Modern Biomedical Industry, Kunming Medical University, China
  • Juanrong Yang Yunnan Provincial Center for Drug Policy Research, College of Modern Biomedical Industry, Kunming Medical University, China
  • Zaixian Yang School of Pharmaceutical Sciences & Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, China
  • Jian Yang Yunnan Provincial Center for Drug Policy Research, College of Modern Biomedical Industry, Kunming Medical University, China https://orcid.org/0009-0000-3271-4735

Keywords:

HIV/AIDS, antiretroviral therapy, efficacy, safety, INSTI- based regimens

Abstract

This comprehensive review and meta-analysis aimed to evaluate the comparative efficacy and safety of various antiretroviral (ARV) therapy regimens for HIV/AIDS treatment based on clinical trial data over 48 and 96 weeks. We conducted a systematic search across multiple databases, identifying 17 randomized controlled trials that met our inclusion criteria. These studies provided data on 12 different ARV regimens, focusing on integrase strand transfer inhibitor (INSTI)-based, non-nucleoside reverse transcriptase inhi-bitor (NNRTI)-based, and protease inhibitor (PI)-based treatments. Efficacy was measured by the percentage of participants achieving viral load suppression below 50 copies/mL, while safety was assessed through the incidence of serious adverse events.  The analysis revealed significant variability in the efficacy and safety profiles of the ARV regimens studied.  INSTI-based treatments, notably elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) and dolutegravir/lamivudine (DTG/3TC), demonstrated the highest levels of viral suppression, maintaining effectiveness at both the 48 and 96-week benchmarks. Notably, a weak positive correlation was identified between the efficacy of these treatments and the incidence of serious adverse events. Despite this correlation, the overall link between a regimen’s efficacy and its safety was found to be weak, highlighting the critical importance of tailoring HIV treatment to the individual patient’s needs and circumstances.  The study underscores the importance of individualizing HIV/AIDS treatment strategies to optimize both efficacy and safety outcomes. While INSTI-based regimens show promise in terms of efficacy, the slightly increased risk of serious adverse events calls for careful consideration in treatment selection and monitoring. Future research should focus on longitudinal studies and the development of predictive models to further refine treatment strategies, helping ensure they are tailored to meet the individual needs of patients living with HIV/AIDS.

References

The Joint United Nations Programme on HIV/AIDS (UNAIDS) [Internet]. Global HIV & AIDS statistics - 2019 fact sheets. 2019 [cited 2020 April 2]. Available from: https://www.unaids.org/en/resources/fact-sheet

INSIGHT START Study Group; Lundgren J, Babiker A, Gordin F, Emery S, Grund B, Sharma S, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373:795-807.

Samji H, Cescon A, Hogg R, Modur S, Althoff K, Buchacz K, et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One. 2013;8:e81355. PubMed PMID: 24367482.

Cohen M, Chen Y, McCauley M, Gamble T, Hosseinipour M, Kumarasamy N, et al. Antiretroviral therapy for the prevention of HIV-1 Transmission. N Engl J Med. 2016;375:830-9.

TEMPRANO ANRS 12136 Study Group; Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, et al. A trial of early antiretroviral and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373:808-22.

Taiwo B, Zheng L, Stefanescu A, Nyaku A, Bezins B, Wallis C, et al. ACTG A5353: a pilot study of dolutegravir plus lamivudine for initial treatment of human immunodeficiency virus-1 (HIV-1)-infected participants with HIV-1 RNA <500000 copies/ml. Clin Infect Dis. 2018;66:1689-97.

Rodger A, Lodwick R, Schechter M, Deeks S, Amin J, Gilson R, et al. Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS. 2013;27:973-9.

Zhao Y, Hohlfeld A, Namale P, Meintjes G, Maartens G, Engel M. Risk of immune reconstitution inflammatory syndrome with integrase inhibitors versus other classes of antiretroviral s: a systematic review and meta-analysis of randomized trials. J Acquir Immune Defic Syndr. 2022;90:232-9.

The Joint United Nations Programme on HIV/AIDS (UNAIDS) [Internet]. The path that ends AIDS: UNAIDS Global AIDS Update 2023. 2023 [cited 2020 April 2]. Available from: https://www.unaids.org/en/resources/documents/2023/2023_global_aids_update

Griessinger J, Hauptstein S, Laffleur F, Netsomboon K, Bernkop-Schnurch A. Evaluation of the impact of multivalent metal ions on the permeation behavior of Dolutegravir sodium. Drug Dev Ind Pharm. 2016;42: 1118-26.

Brief WP. Update of recommendations on first- and second-line antiretroviral regimens. Geneva, Switzerland: World Health Organization; 2019 (WHO/CDS/HIV/19.15).

Patel D, Snedecor S, Tang W, Sudharshan L, Lim J, Cuffe R, et al. 48-week efficacy and safety of dolutegravir relative to commonly used third agents in treatment-naive HIV-1-infected patients: a systematic review and network meta-analysis. PLoS One. 2014;9:e105653. PubMed PMID: 25188312.

Eron J, Orkin C, Gallant J, Molina J, Negredo E, Antinori A, et al. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in

treatment-naive HIV-1 patients. AIDS. 2018;32:1431-42.

Grinsztejn B, De C, Arnold V, Veloso V, Morgado M, Pilotto J, et al. Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 Reflate TB): A multicentre, phase 2, noncomparative, open-label, randomised trial. Lancet Infect Dis. 2014;14:459-67.

Lee Y. An overview of meta-analysis for clinicians. Korean J Intern Med. 2018;33:277-83.

Armijo-Olivo S, Stiles C, Hagen N, Biondo P, Cummings G. Assessment of study quality for systematic reviews: a comparison of the Cochrane Collaboration Risk of Bias Tool and the Effective Public Health Practice Project Quality Assessment Tool: methodological research. J Eval Clin Pract. 2012;18:12-8.

Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021;10:89. PubMed PMID: 33781348.

DeJesus E, Rockstroh J, Henry K, Molina J, Gathe J, Ramanathan S, 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;379:2429-38.

Cahn P, Kaplan R, Sax PE, Squires K, Molina JM, Avihingsanon A, et al. Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial. Lancet HIV. 2017;4:e486-e94. PubMed PMID: 28918877.

Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017;4:e349-e56. PubMed PMID: 28501495.

McCormack S, Best B. Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretroviral s. Clin Pharmacokinet. 2014;53:989-1004.

World Health Organization (WHO). Updated recom-

mendations on first-line and second-line antiretroviral regimens and postexposure prophylaxis and recommendations on early Infant diagnosis of HIV. WHO [Internet]. 2018 [cited 2019 Feb 11]. Available from: http://apps.who.int/iris/bitstream/handle/10665/273632/WHO-CDS-HIV-18.18-eng.pdf?ua=1

Smith S, Zhao X, Passos D, Pye V, Cherepanov P, Lyumkis D, et al. HIV-1 integrase inhibitors with modifications that affect their potencies against drug resistant integrase mutants. ACS Infect Dis. 2021;7:1469-82.

Wohl D, Cohen C, Gallant J, Mills A, Sax P, Dejesus E, et al. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF versus single-tablet regimen efavirenz/emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014;65:e118-20. PubMed PMID: 24256630.

Rockstroh J, DeJesus E, Henry K, Molina J, Gathe J, Ramanathan S, et al. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013;62:483-6.

Arribas J, DeJesus E, van Lunzen J, Zurawski C, Doroana M, Towner W, et al. Simplification to single-tablet regimen of elvitegravir, cobicistat, emtricitabine, tenofovir DF from multi-tablet ritonavir-boosted protease inhibitor plus coformulated emtricitabine and tenofovir DF regimens: week 96 results of STRATEGY-PI. HIV Clin Trials. 2017;18:118-25.

Pozniak A, Flamm J, Antinori A, Bloch M, Ward D, Berenguer J, et al. Switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir DF from non-nucleoside reverse transcriptase inhibitor plus coformulated emtricitabine and tenofovir DF regimens: Week 96 results of STRATEGY-NNRTI. HIV Clin Trials. 2017;18:141-8.

Mills A, Arribas JR, Andrade-Villanueva J, DiPerri G, Van Lunzen J, Koenig E, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active- controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis. 2016;16:43-52.

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Published

2024-10-01

How to Cite

1.
Yan M, Liu Y, He J, Zhou S, Yang J, Yang Z, Yang J. Comparative Analysis of the Efficacy and Safety of HIV/AIDS Treatment Strategies: A Comprehensive Review of Clinical Trial Data. BSCM [Internet]. 2024 Oct. 1 [cited 2024 Dec. 22];63(4):251-65. Available from: https://he01.tci-thaijo.org/index.php/CMMJ-MedCMJ/article/view/270593

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Review Article