Resource and infrastructure challenges on the RESIST-2 Trial: an implementation study of drug resistance genotype-based algorithmic ART switches in HIV-2-infected adults in Senegal

Dana N Raugi, Khardiata Diallo, Mouhamadou Baïla Diallo, Dominique Faye, Ousseynou Cisse, Robert A Smith, Fatima Sall, El Hadji Ibrahima Sall, Khadim Faye, Jean Philippe Diatta, Binetou Diaw, Jacques Sambou, Jean Jacques Malomar, Stephen E Hawes, Moussa Seydi, Geoffrey S Gottlieb, University of Washington-Senegal HIV-2 Study Group, Dana N Raugi, Khardiata Diallo, Mouhamadou Baïla Diallo, Dominique Faye, Ousseynou Cisse, Robert A Smith, Fatima Sall, El Hadji Ibrahima Sall, Khadim Faye, Jean Philippe Diatta, Binetou Diaw, Jacques Sambou, Jean Jacques Malomar, Stephen E Hawes, Moussa Seydi, Geoffrey S Gottlieb, University of Washington-Senegal HIV-2 Study Group

Abstract

Background: Second-line treatment of HIV-2 in resource-limited settings (RLS) is complicated by a lack of controlled trial data, limited availability of HIV-2-active antiretroviral drugs, and inadequate access to drug resistance testing. We conducted an implementation trial of a dried blood spot- (DBS) based, drug resistance genotype-informed antiretroviral therapy (ART) switching algorithm for HIV-2-infected patients in Senegal.

Methods: HIV-2-infected adults initiating or receiving ART through the Senegalese national AIDS program were invited to participate in this single-arm trial. DBS from participants with virologic failure (defined as viral load (VL) > 250 copies/mL after > 6 months on the current ART regimen) were shipped to Seattle for genotypic drug resistance testing. Participants with evidence of drug resistance in protease or reverse transcriptase were switched to new regimens according to a pre-specified algorithm. Participant clinical and immuno-virologic outcomes were assessed, as were implementation challenges.

Results: We enrolled 152 participants. Ten were initiating ART. The remainder were ART-experienced, with 91.0% virologically suppressed (< 50 copies/mL). Problems with viral load testing capability resulted in obtaining VL results for only 227 of 613 (37.0%) participant-visits. Six of 115 participants (5.2%) with VL available after > 6 months on current ART regimen experienced virologic failure, with per-protocol genotypic testing attempted. One additional test was performed for a participant with a VL of 222 copies/mL. Genotypes from three participants showed no evidence of major drug resistance mutations, two showed nucleoside reverse transcriptase inhibitor (NRTI) resistance, one showed both NRTI and protease inhibitor resistance, and one test failed. No integrase inhibitor resistance was observed. Five of six successfully-tested participants switched to the correct regimen or received additional adherence counseling according to the algorithm; the sixth was lost to follow-up. Follow-up VL testing was available for two participants; both of these were virally suppressed (< 10 copies/mL). The trial was terminated early due to the COVID-19 pandemic (which prevented further VL and genotypic testing), planned rollout of dolutegravir-based 1st-line ART, and funding.

Conclusions: The RESIST-2 trial demonstrated that a DBS-based genotypic test can be used to help inform second-line ART decisions as part of a programmatic algorithm in RLS, albeit with significant implementation challenges.

Trial registration: ClinicalTrials.gov NCT03394196 . Registered on January 9, 2018.

Keywords: Antiretroviral therapy; COVID-19; HIV treatment; HIV-2; Point-of-care; Viral suppression.

Conflict of interest statement

SEH has received research grants and research support from the US National Institutes of Health, the University of Washington, and the Bill & Melinda Gates Foundation. MS has received grant funds and clinical support from the ANRS, Glaxo-Smith Kline, and Gilead Sciences. GSG has received research grants and research support from the US National Institutes of Health, the University of Washington, the Bill & Melinda Gates Foundation, Gilead Sciences, Alere Technologies, Merck & Co., Janssen Pharmaceutica, Cerus Corporation, ViiV Healthcare, Bristol-Myers Squibb, Roche Molecular Systems, Abbott Molecular Diagnostics, and THERA Technologies/TaiMed Biologics, Inc. All other authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Algorithm for HIV-2 care in the RESIST-2 Trial for genotype-informed second-line therapy in Senegal. Bracketed steps are ISAARV Standard of Care for HIV-2 infection. Steps in gray box represent RESIST-2 Trial of DBS-based drug resistance genotyping to guide second-line therapy decisions. NRTI nucleoside reverse transcriptase inhibitor; PI protease inhibitor; 3TC lamivudine; AZT zidovudine; DRV/r ritonavir-boosted darunavir; LPV/r ritonavir-boosted lopinavir; RAL raltegravir; TDF tenofovir disoproxil fumarate. *Indicates twice-daily dosing
Fig. 2
Fig. 2
Virologic and drug resistance testing performed in RESIST-2 Trial. *One additional participant had a genotypic test performed with a viral load of 222, which did not meet criteria for virologic failure

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