Indirect Treatment Comparisons of Lenacapavir Plus Optimized Background Regimen Versus Other Treatments for Multidrug-Resistant Human Immunodeficiency Virus

Heavily treatment-experienced (HTE) people with human immunodeficiency virus (HIV) (PWH) may not achieve virologic suppression (VS) with combination antiretroviral therapy due to multidrug resistance (MDR), intolerance, and safety concerns. These PWH often receive highly individualized treatment reg...

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Bibliographic Details
Published in:	Value in health 2023-06, Vol.26 (6), p.810-822
Main Authors:	Chatzidaki, Iro, Curteis, Tristan, Luedke, Hannah, Mezzio, Dylan J., Rhee, Martin S., McArthur, Eve, Eddowes, Lucy A.
Format:	Article
Language:	eng
Subjects:	Anti-HIV Agents - therapeutic use Clinical Protocols Drug Therapy, Combination HIV Infections - drug therapy HIV-1 Humans indirect treatment comparisons lenacapavir multidrug-resistant human immunodeficiency virus
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Summary:	Heavily treatment-experienced (HTE) people with human immunodeficiency virus (HIV) (PWH) may not achieve virologic suppression (VS) with combination antiretroviral therapy due to multidrug resistance (MDR), intolerance, and safety concerns. These PWH often receive highly individualized treatment regimens, but these regimens may not enable PWH to achieve VS, thereby halting disease progression. Novel medications are required for treating individuals with MDR HIV. Lenacapavir (LEN), a first-in-class HIV capsid inhibitor, is under investigation for the treatment of HTE individuals with MDR HIV in the phase 2/3 CAPELLA study. This study aimed to compare LEN plus optimized background regimen (OBR) with fostemsavir (FTR) + OBR, ibalizumab (IBA) + OBR, and OBR alone in terms of VS, CD4 cell count change from baseline, immunologic recovery, and discontinuation due to adverse events, using indirect treatment comparisons. A systematic review identified clinical evidence on HIV-1 treatments in HTE PWH. A feasibility assessment evaluated the identified studies for indirect treatment comparison analyses based on population characteristics, interventions, comparators, and outcomes of interest. Unanchored simulated treatment comparisons of LEN + OBR versus comparators were conducted. LEN + OBR had 6.57 times higher odds of VS at weeks 24 to 28 than FTR + OBR (95% confidence interval [CI] 1.34-32.28), 8.93 times higher odds of VS than IBA + OBR (95% CI 2.07-38.46), and 12.74 times higher odds of VS than OBR alone (95% CI 1.70-95.37). Change from baseline in CD4 cell count was similar across LEN + OBR, FTR + OBR, and IBA + OBR. LEN + OBR has statistically significantly greater odds of VS at weeks 24 to 28 than its comparators and represents a novel treatment for people with MDR HIV. •Available evidence on the efficacy and effectiveness of different therapies in heavily treatment-experienced people with human immunodeficiency virus (HIV) is sparse.•This is the first analysis that provides comparative treatment estimates that can be used alongside other outcomes to support decisions regarding the care of people with multidrug-resistant HIV.•We have shown that lenacapavir + optimized background regimen is favored over key comparators in terms of achieving virologic suppression and therefore has potential to reduce the burden associated with virologic failure in people with multidrug-resistant HIV.
ISSN:	1098-3015 1524-4733