Impact of Treatment Adherence on Efficacy of Dolutegravir + Lamivudine and Dolutegravir + Tenofovir Disoproxil Fumarate/Emtricitabine: Pooled Week 144 Analysis of the GEMINI-1 and GEMINI-2 Clinical Studies

Fernvik, Eva; Sierra Madero, Juan; Espinosa, Nuria; Gulminetti, Roberto; Hagins, Debbie; Tsai, Hung-Chin; Man, Choy; Sievers, Jörg; Grove, Richard; Zolopa, Andrew; Wynne, Brian; van Wyk, Jean; Ait-Khaled, Mounir

doi:10.1097/qai.0000000000003280

Cited by 2 publications

(1 citation statement)

References 11 publications

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“…Even more objective measures such as electronic monitoring and pill counting have challenges, where the latter can generate inaccurate estimates of adherence due to factors such as surplus medication or the assumption that a dose removed from its container is equivalent to an individual taking the medication. In the phase 3 GEMINI-1 and GEMINI-2 studies, a post hoc analysis showed that rates of virologic suppression were lower among those with more suspected missed doses [78]. Importantly, the 1 participant in the GEMINI studies who developed an emergent INSTI RAM (R263R/K) had a previous elevated viral load attributed to treatment non-adherence [19].…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Literature Review of Treatment-Emergent Integrase Resistance with Dolutegravir-Based Regimens in Real-World Settings

Henegar,

Letang,

Wang

et al. 2023

Viruses

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After a decade of dolutegravir (DTG) use in various antiretroviral therapy combinations and in diverse populations globally, it is critical to identify HIV strains with reduced drug susceptibility and monitor emergent resistance in people living with HIV who experience virologic failure while on DTG-based regimens. We searched the PubMed, Embase, and Cochrane databases to identify studies that reported DTG resistance-associated mutations (RAMs) emerging under selection pressure. Our review showed that RAMs conferring resistance to DTG were rare in 2-drug and 3-drug regimens used in real-world cohorts, corroborating data from clinical trials. The potency of DTG in maintaining virologic suppression was demonstrated, even in cases of pre-existing resistance to companion drugs in the regimen. Estimates of DTG RAMs depended on the population and certain risk factors, including monotherapy, baseline resistance or lack of genotypic testing, treatment history and prior virologic failure, and suboptimal treatment adherence. The RAMs detected after virologic failure, often in heavily treatment-experienced individuals with prior exposure to integrase strand transfer inhibitors, were G118R, E138K, G140A/C/R/S, Q148H/K/R, N155H, and R263K. Overall, these data highlight the durable effectiveness and high barrier to resistance of DTG as part of combination antiretroviral therapy in a wide variety of settings.

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Section: Discussionmentioning

confidence: 99%

A Comprehensive Literature Review of Treatment-Emergent Integrase Resistance with Dolutegravir-Based Regimens in Real-World Settings

Henegar,

Letang,

Wang

et al. 2023

Viruses

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Efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir-based three-drug regimens in people with HIV with varying adherence to antiretroviral therapy

Andreatta,

Sax,

Wohl

et al. 2024

Journal of Antimicrobial Chemotherapy

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Objective Five Phase 3 bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) clinical studies demonstrated that the efficacy of B/F/TAF was non-inferior to dolutegravir (DTG) + 2 NRTIs. We retrospectively assessed drug adherence and effect on virologic outcomes. Methods Studies (NCT02607930, NCT02607956, NCT03547908, NCT02603120 and NCT03110380) were double-blind, placebo-controlled and enrolled treatment-naïve or virologically suppressed adults. Adherence was calculated by pill count from returned pill bottles; virologic outcome was assessed by last on-treatment HIV-1 RNA. Results Altogether, 2622 participants (B/F/TAF: n = 1306; DTG + 2 NRTIs: n = 1316) were categorized as having high (≥95%), intermediate (≥85% to <95%) or low (<85%) adherence. Through Week 48, low adherence was observed in 46 (3.5%) participants in the B/F/TAF group (78% median adherence) and 69 (5.2%) in the DTG + 2 NRTI group (80% median adherence). Overall, 1287 (98.5%) participants in the B/F/TAF group and 1292 (98.2%) in the DTG + 2 NRTI group had virologic suppression (VS; HIV-1 RNA < 50 copies/mL) through Week 48. VS in participants with low adherence versus high or intermediate adherence was similar in the B/F/TAF group, but lower in the DTG + 2 NRTI group (P ≤ 0.002). Similar results were observed at Weeks 96 and 144. Two participants (<95% adherence) in the DTG + 2 NRTI group receiving DTG and abacavir/lamivudine developed M184V; there was no treatment-emergent resistance to B/F/TAF. Conclusions Participants with suboptimal (<85%) adherence to B/F/TAF maintained high levels of VS, whereas suboptimal DTG + 2 NRTI adherence was associated with lower VS.

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Impact of Treatment Adherence on Efficacy of Dolutegravir + Lamivudine and Dolutegravir + Tenofovir Disoproxil Fumarate/Emtricitabine: Pooled Week 144 Analysis of the GEMINI-1 and GEMINI-2 Clinical Studies

Cited by 2 publications

References 11 publications

A Comprehensive Literature Review of Treatment-Emergent Integrase Resistance with Dolutegravir-Based Regimens in Real-World Settings

A Comprehensive Literature Review of Treatment-Emergent Integrase Resistance with Dolutegravir-Based Regimens in Real-World Settings

Efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir-based three-drug regimens in people with HIV with varying adherence to antiretroviral therapy

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