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Comparative Study
. 2025 Aug;26(8):1184-1198.
doi: 10.1111/hiv.70050. Epub 2025 May 27.

Comparison of treatment-emergent resistance-associated mutations and discontinuation due to adverse events among integrase strand transfer inhibitor-based single-tablet regimens and cabotegravir + rilpivirine for the treatment of virologically suppressed people with HIV: A systematic literature review and network meta-analysis

Ishfaq Rashid  1 , Nathan R Unger  2 , Connor Willis  1 , Teerapon Dhippayom  1   3 , Moti Ramgopal  4 , Elizabeth M Sherman  5 , Nicholas Yared  6 , Rachel Safran  7 , Edwin Swiatlo  8 , Amy R Weinberg  2 , Soodi Navadeh  2 , Howard Weston Schmutz  1 , Nathorn Chaiyakunapruk  1   9
Affiliations
Comparative Study

Comparison of treatment-emergent resistance-associated mutations and discontinuation due to adverse events among integrase strand transfer inhibitor-based single-tablet regimens and cabotegravir + rilpivirine for the treatment of virologically suppressed people with HIV: A systematic literature review and network meta-analysis

Ishfaq Rashid et al. HIV Med. 2025 Aug.

Abstract

Objective: This study evaluated rates of treatment-emergent resistance-associated mutations (TE-RAMs) and discontinuation due to adverse events (DC-AEs) across integrase strand transfer inhibitor (INSTI)-based single-tablet regimens and injectable cabotegravir + rilpivirine (CAB + RPV) in virologically suppressed people with HIV.

Methods: A systematic literature review was conducted for phase 2-4 randomized controlled trials with ≥48 weeks of follow-up involving virologically suppressed people with HIV aged ≥12 years and published January 2003-March 2024. A random-effects network meta-analysis estimated comparative rates of TE-RAMs and DC-AEs among regimens at 48 weeks. Risk of bias and strength of evidence were assessed using Cochrane RoB and CINeMA, respectively.

Results: Fourteen (7509 participants) and nine (4656 participants) studies were included in the TE-RAMs and DC-AEs analyses, respectively. No significant differences in rates of TE-RAMs were observed; risk ratios (RRs) for TE-RAMs for bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) and CAB + RPV every 4 weeks (Q4W) versus CAB + RPV every 8 weeks (Q8W) were 0.22 (95% CI, 0.02-2.04), 0.22 (95% CI, 0.00-19.85) and 0.40 (95% CI, 0.14-1.09). Compared with CAB + RPV Q4W and Q8W, DC-AEs were significantly lower with B/F/TAF (RR, 0.15 [95% CI, 0.03-0.75] and RR, 0.16 [95% CI, 0.04-0.67], respectively) and DTG/ABC/3TC (RR, 0.05 [95% CI, 0.01-0.48] and RR, 0.05 [95% CI, 0.01-0.46], respectively).

Conclusions: In virologically suppressed people with HIV, switching to CAB + RPV Q8W yielded a non-significant increased risk of TE-RAMs compared with INSTI-based 2- and 3-drug regimens and CAB + RPV Q4W. Both CAB + RPV Q4W and Q8W had significantly higher risks of DC-AEs than B/F/TAF and DTG/ABC/3TC. Findings highlight the importance of considering both resistance and tolerability when switching regimens.

Keywords: HIV; antiretroviral therapy; drug resistance; integrase inhibitor; single‐tablet regimen.

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Conflict of interest statement

IR, CW, HWS and NC are employees of the University of Utah, which received a research grant from Gilead Sciences, Inc., to conduct this work; CW also received funding for travel and conference registration fees from Gilead Sciences, Inc.; and HWS is a Utah Academy of Managed Care Pharmacy legislative chair. NRU, ARW and SN are employees of and may own stocks or stock options in Gilead Sciences, Inc. TD is an adjunct faculty member of the University of Utah, which received a research grant from Gilead Sciences, Inc., to conduct this work. MR received consulting fees from AbbVie, Gilead Sciences, Inc., Merck and ViiV Healthcare; and received honoraria from Gilead Sciences, Inc., and ViiV Healthcare. NY received honoraria/consulting fees from Astellas Pharma US, Inc., and ViiV Healthcare; and received food/beverage reimbursement from Gilead Sciences, Inc., and ViiV Healthcare. RS received speakers bureau honoraria from Gilead Sciences, Inc.; received research contracts paid to her institution from Gilead Sciences, Inc., Merck and Roche; she received a project fee from IMO Core; and is a board member of the Spokane AIDS Network. EMS and ES have no conflicts to report.

Figures

FIGURE 1
FIGURE 1
PRISMA flow chart. aRegisters refers to clinical trial registries (e.g., ClinicalTrials.gov). bCovidence automation tool. INSTI, integrase strand transfer inhibitor; PRISMA, Preferred Reporting Items for Systematic reviews and Meta‐Analyses; RCT, randomized controlled trial; STR, single‐tablet regimen.
FIGURE 2
FIGURE 2
Network map of TE‐RAMs at 48 weeks. Node size is proportional to the number of participants across all included studies for an intervention, and line thickness is proportional to the number of studies that compared the two interventions. B/F/TAF, bictegravir/emtricitabine/tenofovir alafenamide; bPI, boosted protease inhibitor; CAB + RPV, cabotegravir + rilpivirine; DTG, dolutegravir; DTG/3TC, dolutegravir/lamivudine; DTG/ABC/3TC, dolutegravir/abacavir/lamivudine; DTG/RPV, dolutegravir/rilpivirine; E/C/F/TXF, elvitegravir/cobicistat/emtricitabine/(tenofovir disoproxil fumarate or tenofovir alafenamide); EFV/FTC/TDF, efavirenz/emtricitabine/tenofovir disoproxil fumarate; NRTI, nucleoside reverse transcriptase inhibitor; Q4W, every 4 weeks; Q8W, every 8 weeks; TE‐RAM, treatment‐emergent resistance‐associated mutation.
FIGURE 3
FIGURE 3
Network map of DC‐AEs at 48 weeks. Node size is proportional to the number of participants across all included studies for an intervention, and line thickness is proportional to the number of studies that compared the two interventions. B/F/TAF, bictegravir/emtricitabine/tenofovir alafenamide; bPI, boosted protease inhibitor; CAB + RPV, cabotegravir + rilpivirine; DC‐AEs, discontinuation due to adverse events; DTG, dolutegravir; DTG/ABC/3TC, dolutegravir/abacavir/lamivudine; DTG/RPV, dolutegravir/rilpivirine; E/C/F/TXF, elvitegravir/cobicistat/emtricitabine/(tenofovir disoproxil fumarate or tenofovir alafenamide); NRTI, nucleoside reverse transcriptase inhibitor; Q4W, every 4 weeks; Q8W, every 8 weeks.
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References

    1. US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents . Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Accessed October 17, 2024. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/ad...
    1. Altice F, Evuarherhe O, Shina S, Carter G, Beaubrun AC. Adherence to HIV treatment regimens: systematic literature review and meta‐analysis. Patient Prefer Adherence. 2019;13:475‐490. - PMC - PubMed
    1. Overton ET, Richmond G, Rizzardini G, et al. Long‐acting cabotegravir and rilpivirine dosed every 2 months in adults with human immunodeficiency virus 1 type 1 infection: 152‐week results from ATLAS‐2M, a randomized, open‐label, phase 3b, noninferiority study. Clin Infect Dis. 2023;76(9):1646‐1654. - PMC - PubMed
    1. van Welzen BJ, Van Lelyveld SFL, Ter Beest G, et al. Virological failure after switch to long‐acting cabotegravir and rilpivirine injectable therapy: an in‐depth analysis. Clin Infect Dis. 2024;79(1):189‐195. - PMC - PubMed
    1. Kityo C, Mambule IK, Musaazi J, et al. Switch to long‐acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): week 48 results from a randomised, multicentre, open‐label, non‐inferiority trial. Lancet Infect Dis. 2024;24(10):1083‐1092. - PubMed

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