TY - JOUR
T1 - Withdrawing inactive NRTIs in HIV-1 subjects with suppressed viraemia: A randomized trial
AU - Llibre, Josep M.
AU - Alvarez, Hortensia
AU - Antela, Antonio
AU - Toro, Jessica
AU - Payeras, Antoni
AU - Jesús Pérez-Elías, M.
AU - Imaz, Arkaitz
AU - Masià, Mar
AU - Pérez-Alvarez, Núria
AU - Burgos, Joaquin
AU - Clotet, Bonaventura
AU - Bravo, Isabel
AU - Ayestaran, Aintzane
AU - Podzamczer, Daniel
AU - Domingo, Pere
AU - Fernández, Irene
AU - Crespo, Manel
AU - Valero, Silvia
AU - Masià, Mar
AU - Pérez-Elías, Maria Jesús
AU - Díaz, Alberto
AU - Yzusqui, Miguel
AU - Ana Isabel Mariño, null
AU - Hernández-Quero, José
AU - Moreno, Juan González
PY - 2016/5/1
Y1 - 2016/5/1
N2 - © The Author 2016. Background: Extensively pretreated subjects with virological failure (VF) may receive salvage regimens containing NRTIs with only residual or no activity. Once virological suppression is achieved, their contribution remains elusive. Methods: This was a multicentre, randomized, prospective study. Subjects with at least one prior VF, HIV-1 RNA <50 copies/mL for ≥6 months and receiving a regimen with at least two active drugs (one of them a boosted PI) were randomized 1:1 to stop (experimental arm) or maintain (control arm) NRTIs. EudraCT: 2012-000198-21. Results: Ninety subjects were randomized (experimental, n=45; and control, n=45). The mean age was 50 years, 80% were male, the mean CD4+ cell count was 542 cells/mm3 and the median number of prior VFs was 3. Seventy-four subjects (82%) harboured the mutation M184V/I and the median number of thymidine- associated mutations was 3 (IQR: 0-4). In the experimental arm, thirty-two (71%) subjects removed one NRTI and 13 (29%) subjects removed two. Twenty-two of 45 (49%) discontinued tenofovir disoproxil fumarate. Forty-one of 45 (91.1%, experimental arm) and 44 of 45 (97.8%, control arm) had HIV-1 RNA <50 copies/mL at 48 weeks (difference: 26.7%; 95% CI: 217.4, 4.1). In a post-hoc analysis allowing NRTI reintroduction, efficacy rates were 95.6% and 97.8%, respectively (difference: 22.2%; 95% CI: 27.2, 2.7). Rates of discontinuation at 48 weeks were 2% in both arms. One subject developed a late VF with resistance selection. Conclusions: In patients receiving a successful multidrug salvage regimen with at least two active drugs (one a boosted PI), the withdrawal of inactive NRTIs was safe, rates of VF were low and drug resistance was uncommon at 48 weeks in this small study. This strategy could potentially prevent long-term toxicities, reduce the number of drugs and reduce costs if non-inferiority was met in a fully powered trial.
AB - © The Author 2016. Background: Extensively pretreated subjects with virological failure (VF) may receive salvage regimens containing NRTIs with only residual or no activity. Once virological suppression is achieved, their contribution remains elusive. Methods: This was a multicentre, randomized, prospective study. Subjects with at least one prior VF, HIV-1 RNA <50 copies/mL for ≥6 months and receiving a regimen with at least two active drugs (one of them a boosted PI) were randomized 1:1 to stop (experimental arm) or maintain (control arm) NRTIs. EudraCT: 2012-000198-21. Results: Ninety subjects were randomized (experimental, n=45; and control, n=45). The mean age was 50 years, 80% were male, the mean CD4+ cell count was 542 cells/mm3 and the median number of prior VFs was 3. Seventy-four subjects (82%) harboured the mutation M184V/I and the median number of thymidine- associated mutations was 3 (IQR: 0-4). In the experimental arm, thirty-two (71%) subjects removed one NRTI and 13 (29%) subjects removed two. Twenty-two of 45 (49%) discontinued tenofovir disoproxil fumarate. Forty-one of 45 (91.1%, experimental arm) and 44 of 45 (97.8%, control arm) had HIV-1 RNA <50 copies/mL at 48 weeks (difference: 26.7%; 95% CI: 217.4, 4.1). In a post-hoc analysis allowing NRTI reintroduction, efficacy rates were 95.6% and 97.8%, respectively (difference: 22.2%; 95% CI: 27.2, 2.7). Rates of discontinuation at 48 weeks were 2% in both arms. One subject developed a late VF with resistance selection. Conclusions: In patients receiving a successful multidrug salvage regimen with at least two active drugs (one a boosted PI), the withdrawal of inactive NRTIs was safe, rates of VF were low and drug resistance was uncommon at 48 weeks in this small study. This strategy could potentially prevent long-term toxicities, reduce the number of drugs and reduce costs if non-inferiority was met in a fully powered trial.
U2 - 10.1093/jac/dkv461
DO - 10.1093/jac/dkv461
M3 - Article
VL - 71
SP - 1346
EP - 1351
IS - 5
ER -
