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
Article
em En
| SES-SP, SESSP-IIERPROD, SES-SP
| ID: biblio-1016849
Biblioteca responsável:
BR31.1
Localização: 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 resistancePalavras-chave
Texto completo:
1
Coleções:
06-national
/
BR
Base de dados:
SES-SP
/
SESSP-IIERPROD
Assunto principal:
Resistência a Medicamentos
/
HIV
/
Terapia Antirretroviral de Alta Atividade
Tipo de estudo:
Clinical_trials
Limite:
Child
/
Humans
Idioma:
En
Revista:
J. acquir immune defic. syndr
Ano de publicação:
2015
Tipo de documento:
Article