HIV-1 drug resistance and second-line treatment in children randomized to switch at low versus higher RNA thresholds
J. acquir immune defic. syndr
; 70(1): 42-53, Sept. 2015. ilus, tab
Artículo
en Inglés
| Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP
| ID: biblio-1016849
Biblioteca responsable:
BR31.1
Ubicación: BR31.1; 2015_P-031
ABSTRACT
BACKGROUND:
The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold.METHODS:
PENPACT-1 had a 2 × 2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, and switch at a 1000 copies/mL versus 30,000 copies/mL threshold. Switch criteria were not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or Center for Disease Control and Prevention stage C event. Resistance tests were performed on samples ≥1000 copies/mL before switch, resuppression, and at 4-years/trial end.RESULTS:
Sixty-seven children started PI-based ART and were randomized to switch at 1000 copies/mL (PI-1000), 64 PIs and 30,000 copies/mL (PI-30,000), 67 NNRTIs and 1000 copies/mL (NNRTI-1000), and 65 NNRTI and 30,000 copies/mL (NNRTI-30,000). Ninety-four (36%) children reached the 1000 copies/mL switch criteria during 5-year follow-up. In 30,000 copies/mL threshold arms, median time from 1000 to 30,000 copies/mL switch criteria was 58 (PI) versus 80 (NNRTI) weeks (P = 0.81). In NNRTI-30,000, more nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000 copies/mL (23% NNRTI-1000, 27% NNRTI-30,000). Sixty-two children started abacavir + lamivudine, 166 lamivudine + zidovudine or stavudine, and 35 other NRTIs. The abacavir + lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30,000, 64% NNRTI-1000, and 100% NNRTI-30,000 were <400 copies/mL 24 weeks later.CONCLUSIONS:
Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line. An abacavir + lamivudine NRTI combination seemed protective against development of NRTI resistance
Texto completo:
Disponible
Colección:
Bases de datos nacionales
/
Brasil
Base de datos:
Sec. Est. Saúde SP
/
SESSP-IIERPROD
Asunto principal:
Resistencia a Medicamentos
/
VIH
/
Terapia Antirretroviral Altamente Activa
Tipo de estudio:
Ensayo clínico controlado
Límite:
Niño
/
Humanos
Idioma:
Inglés
Revista:
J. acquir immune defic. syndr
Año:
2015
Tipo del documento:
Artículo
Institución/País de afiliación:
Harvard T.H. Chan School of Public Health/US
/
INSERM/FR
/
Imperial College London/GB
/
NSERM/FR
/
Seattle Children's Hospital/US
/
Secretaria de Estado da Saúde. São Paulo/BR
/
University College London/GB
/
University of North Carolina at Chapel Hill/US