Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
Impact of Proviral-DNA M184V/I on 96-Week Outcomes of DTG/3TC Maintenance Therapy: Results From the VOLVER Clinical Trial.
СтатьяМногоцентровое исследованиеКлиническое исследование II фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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De Lagarde María, De Miguel Rosa, Sigcha Mayra A, Blanco Jose L, Pinto-Martinez Adriana, Montejano Rocío, Gutiérrez Liarte Angela, Navarro-Soler Roser, Cañas-Ruano Esperanza, Inciarte Alexis, Martin-Carbonero Luz, Imaz Arkaitz, Hernández Gutiérrez Cristina, Ocampo Antonio, de Miguel Marta, Delgado Rafael, Pulido Federico, Arribas Jose R, VOLVER GESIDA 11820 Study Group
Аннотация
BACKGROUND: The effect of archived lamivudine resistance mutations in the efficacy of dolutegravir plus lamivudine (DTG/3TC) remains unclear. We evaluated whether proviral-DNA M184V/I detection is associated with virological outcomes in the VOLVER-GESIDA 11820 study.
METHODS: This open-label, single-arm, multicenter phase IIa trial (NCT04880785) enrolled virologically suppressed adults with documented or suspected historical lamivudine resistance if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Participants switched to DTG/3TC and were followed through week 96. Proviral-DNA M184V/I was assessed retrospectively by next-generation sequencing (NGS) of peripheral blood mononuclear cells at baseline and week 96.
RESULTS: Of 121 participants, 94% had documented historical M184V/I. Proviral-DNA NGS detected M184V/I at ≥5% frequency in 37 (30.6%; 32 M184V, 5 M184I) at baseline and/or week 96: 12 only at baseline, 13 only at week 96, and 12 at both timepoints. Two virological failures occurred within the first 48 weeks; none were observed thereafter. No treatment-emergent resistance was detected. In the ITT-e population (Snapshot analysis), HIV-1 RNA <50 copies/mL at week 96 was maintained in 85.7% (72/84) with no detection of M184V/I, 66.7% (8/12) with detection only at baseline, and 100% with detection only at week 96 (13/13) or both time points (12/12). Among those with M184V/I at both time points, the proportion of proviral sequences carrying the mutation increased from 30% to 45% (P = .0037).
CONCLUSIONS: Proviral-DNA M184V/I detection was not associated with virological outcomes in participants receiving DTG/3TC supporting its limited clinical value in this specific setting.
METHODS: This open-label, single-arm, multicenter phase IIa trial (NCT04880785) enrolled virologically suppressed adults with documented or suspected historical lamivudine resistance if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Participants switched to DTG/3TC and were followed through week 96. Proviral-DNA M184V/I was assessed retrospectively by next-generation sequencing (NGS) of peripheral blood mononuclear cells at baseline and week 96.
RESULTS: Of 121 participants, 94% had documented historical M184V/I. Proviral-DNA NGS detected M184V/I at ≥5% frequency in 37 (30.6%; 32 M184V, 5 M184I) at baseline and/or week 96: 12 only at baseline, 13 only at week 96, and 12 at both timepoints. Two virological failures occurred within the first 48 weeks; none were observed thereafter. No treatment-emergent resistance was detected. In the ITT-e population (Snapshot analysis), HIV-1 RNA <50 copies/mL at week 96 was maintained in 85.7% (72/84) with no detection of M184V/I, 66.7% (8/12) with detection only at baseline, and 100% with detection only at week 96 (13/13) or both time points (12/12). Among those with M184V/I at both time points, the proportion of proviral sequences carrying the mutation increased from 30% to 45% (P = .0037).
CONCLUSIONS: Proviral-DNA M184V/I detection was not associated with virological outcomes in participants receiving DTG/3TC supporting its limited clinical value in this specific setting.