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. 2023 Oct 27;10(11):ofad526.
doi: 10.1093/ofid/ofad526. eCollection 2023 Nov.

Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis

Madhusudan Kabra  1 , Tristan J Barber  2   3 , Clotilde Allavena  4 , Anne-Geneviève Marcelin  5 , Simona Di Giambenedetto  6 , Juan Pasquau  7 , Nicola Gianotti  8 , Josep M Llibre  9 , David Rial-Crestelo  10   11 , Rosa De Miguel-Buckley  11   12 , Gary Blick  13 , Matthew Turner  14 , Cale Harrison  14 , Tammy Wynne  14 , Gustavo Verdier  15 , Chris M Parry  1 , Bryn Jones  1 , Chinyere Okoli  1 , Cynthia Donovan  16 , Julie Priest  16 , Emilio Letang  17
Affiliations

Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis

Madhusudan Kabra et al. Open Forum Infect Dis. .

Abstract

Background: To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review.

Methods: Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks.

Results: Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%-3.81%; interventional: 0.00%) and without (real-world: 0.73%-2.37%). Meta-analysis-estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00-.04], 0.03 [.01-.06], and 0.04 [.01-.07]; interventional: 0.00 [.00-.02], 0.00 [.00-.01], and 0.00 [.00-.03]) and without (real-world: 0.00 [.00-.02], 0.02 [.01-.04], and 0.02 [.00-.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I.

Conclusions: Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options.

Keywords: HIV drug resistance; M184V/I; dolutegravir/lamivudine; integrase inhibitor; real-world evidence.

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Conflict of interest statement

Potential conflicts of interest. M. K. was a complimentary worker for ViiV Healthcare at the time of the analysis. G. V. is an employee of ViiV Healthcare. C. M. P., B. J., C. O., J. Pr., and E. L. are employees of ViiV Healthcare and own stock in GSK. T. J. B. has received grants from Gilead, MSD, Roche, and ViiV Healthcare; consulting fees and honoraria from Gilead, GSK, Janssen, MSD, Roche, Theratechnologies, and ViiV Healthcare; and travel support from Gilead and ViiV Healthcare. C. A. has received honoraria from Gilead, MSD, and ViiV Healthcare; has received travel support from Gilead and MSD; and is a member of the CPP Ouest IV Ethics Committee. A.-G. M. has received grants and honoraria from Gilead, MSD, and ViiV Healthcare; consulting fees from GSK; and travel support from Gilead. J. Pa. has received honoraria from Gilead, Janssen-Cilag, MSD, and ViiV Healthcare and travel support from Gilead and Janssen-Cilag. N. G. has received grants, honoraria, and travel support from Gilead, Janssen-Cilag, MSD, and ViiV Healthcare. J. M. L. has received grants from Gilead and ViiV Healthcare; has received speaker honoraria from Gilead, Janssen-Cilag, and ViiV Healthcare; and is a member of the Spanish Antiretroviral Treatment Guidelines panel. D. R.-C. has received honoraria from Gilead and ViiV Healthcare and travel support from Gilead. R. D. M.-B. has received speaker fees from Gilead and ViiV Healthcare and travel support from ViiV Healthcare. G. B. has received honoraria and travel support from ViiV Healthcare. M. T., C. H., and T. W. are employees of HEOR Ltd, which received funding from ViiV Healthcare to support this analysis. S. D. G. reports no potential conflicts.

Figures

Figure 1.
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowcharts for RWE studies (A) and interventional studies (B). aOthers indicates records that were not classified into key categories. bTwo lead publications did not report all information reported within the analyses and were each manually supplemented with data from an additional publication from the same cohort. Abbreviations: 3TC, lamivudine; ACHA, Asian Conference on Hepatitis and AIDS; ASHM, Australasian HIV & AIDS Conference; ASICON, National Conference of AIDS Society of India; BASHH, British Association for Sexual Health and HIV; BHIVA, British HIV Association; CAHR, Canadian Conference on HIV/AIDS Research; CROI, Conference on Retroviruses and Opportunistic Infections; DTG, dolutegravir; GeSIDA, Grupo de Estudio del SIDA-SEIMC; HIV/HEP, HIV & Hepatitis in the Americas; HIV-NAT, The HIV Netherlands Australia Thailand Research Collaboration; IAS/IAC, International AIDS Society/International AIDS Conference; ICAR, International Conference on Antiviral Research; ICASA, International Conference on AIDS and STIs in Africa; ICID, International Congress on Infectious Diseases; JSAR, Japanese Society for AIDS Research; KAP, Kenya Association of Physicians; PWH, people with human immunodeficiency virus type 1; RWE, real-world evidence; SFLS, Société Française de Lutte contre le Sida; STI, sexually transmitted infection.
Figure 2.
Figure 2.
Meta-analysis estimates of virologic failure (VF) incidence after switch to dolutegravir plus lamivudine in people with human immunodeficiency virus type 1 with (A) and without (B) historical M184V/I from systematic literature review–identified real-world evidence studies, inclusive of all VF definitions. Abbreviations: CI, confidence interval; PWH, people with human immunodeficiency virus type 1; VF, virologic failure; Wt, weight.
Figure 3.
Figure 3.
Meta-analysis estimates of virologic failure (VF) incidence after switch to dolutegravir plus lamivudine in people with human immunodeficiency virus type 1 with historical M184V/I from targeted literature review–identified interventional studies, inclusive of all VF definitions. Abbreviations: CI, confidence interval; PWH, people with human immunodeficiency virus type 1; VF, virologic failure; Wt, weight.
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