The Journal of infectious diseases · 2025
Resistance Analyses in Heavily Treatment-Experienced People With HIV Treated With the Novel HIV Capsid Inhibitor Lenacapavir After 2 Years.
СтатьяКлиническое исследование II фазыКлиническое исследование III фазыНазвание и аннотация: Перевод в очереди
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Margot Nicolas A, Jogiraju Vamshi, Pennetzdorfer Nina, Naik Vidula, VanderVeen Laurie A, Ling John, Singh Renu, Dvory-Sobol Hadas, Ogbuagu Onyema, Segal-Maurer Sorana, Molina Jean-Michel, Rhee Martin S, Callebaut Christian
Аннотация
BACKGROUND: Lenacapavir is a highly potent first-in-class inhibitor of HIV-1 capsid that was approved for the treatment of heavily treatment-experienced people with HIV-1 harboring multidrug-resistant virus, and it is used in combination with an optimized background regimen (OBR). Resistance analyses conducted after 2 years of lenacapavir treatment in the phase 2/3 CAPELLA study are described.
METHODS: CAPELLA enrollment consisted of viremic cases of heavily treatment-experienced people with HIV-1 and resistance to ≥2 drugs per class in at least 3 of the 4 main drug classes. Postbaseline resistance in participants experiencing virologic failure was evaluated by resistance assays (HIV-1 capsid, protease, reverse transcriptase, and integrase genotypic/phenotypic tests). Adherence to OBR was assessed by plasma drug measurement via liquid chromatography-tandem mass spectrometry.
RESULTS: After 2 years, lenacapavir + OBR treatment led to HIV-1 RNA suppression in 82% of participants (missing = excluded). Treatment-emergent capsid resistance occurred in 19% (14/72) of participants, including capsid mutations M66I, Q67H/K/N, K70H/N/R/S, and/or N74D/H/K, which were all associated with functional lenacapavir monotherapy. Seven participants with lenacapavir resistance reattained HIV-1 RNA <50 copies/mL upon OBR resumption or change while maintaining lenacapavir treatment.
CONCLUSIONS: Emergence of lenacapavir resistance after 2 years in CAPELLA was a consequence of functional lenacapavir monotherapy. In half of participants with lenacapavir resistance, continued treatment with lenacapavir + active OBR led to HIV-1 RNA resuppression.
METHODS: CAPELLA enrollment consisted of viremic cases of heavily treatment-experienced people with HIV-1 and resistance to ≥2 drugs per class in at least 3 of the 4 main drug classes. Postbaseline resistance in participants experiencing virologic failure was evaluated by resistance assays (HIV-1 capsid, protease, reverse transcriptase, and integrase genotypic/phenotypic tests). Adherence to OBR was assessed by plasma drug measurement via liquid chromatography-tandem mass spectrometry.
RESULTS: After 2 years, lenacapavir + OBR treatment led to HIV-1 RNA suppression in 82% of participants (missing = excluded). Treatment-emergent capsid resistance occurred in 19% (14/72) of participants, including capsid mutations M66I, Q67H/K/N, K70H/N/R/S, and/or N74D/H/K, which were all associated with functional lenacapavir monotherapy. Seven participants with lenacapavir resistance reattained HIV-1 RNA <50 copies/mL upon OBR resumption or change while maintaining lenacapavir treatment.
CONCLUSIONS: Emergence of lenacapavir resistance after 2 years in CAPELLA was a consequence of functional lenacapavir monotherapy. In half of participants with lenacapavir resistance, continued treatment with lenacapavir + active OBR led to HIV-1 RNA resuppression.