Drug resistance and viral evolution in plasma and peripheral blood cells during structured treatment interruption (STI) and non-interrupted HAART.
Curr HIV Res
; 5(2): 235-50, 2007 Mar.
Article
em En
| MEDLINE
| ID: mdl-17346137
ABSTRACT
BACKGROUND:
Highly active antiretroviral therapy (HAART) can successfully reduce plasma and tissue levels of HIV-1 RNA and results in reductions in HIV-related morbidity and mortality, but the slow viral evolution during therapy in cellular reservoirs is a continuing problem. In addition, little remains known how viral evolutionary process may differ between cell-free and cell-associated compartments, over time, in vivo in patients receiving HAART or STI.OBJECTIVES:
The main objectives of this study were to assess viral replication kinetics, drug resistance and viral evolution during HAART and STI. STUDYDESIGN:
We have conducted a longitudinal study of virus culture kinetics in vitro, molecular analysis of uncultured HIV-1 variants from plasma and PBMC of 6 patients on HAART, 4 patients on STI, and 6 from treatment-naïve patients.RESULTS:
Our data suggest that drug resistance mutations remained compartmentalized between plasma and PBMC. The divergent distribution of resistance mutations between plasma and PBMC coincided with divergent env gene evolution in these compartments. In contrast, the HIV strains from therapy-naive patients showed tight genetic and phylogenetic concordance between plasma and PBMC. Both STI and non-STI groups showed the presence of resistance mutations to both RT and protease inhibitors, which correlated with inadequate suppression of viremia and partially with the virus culture isolation in vitro.CONCLUSIONS:
Overall, STI for HIV patients has no added advantage over regular HAART at the virologic level and in the diminution of resistance mutations that result in therapy failure. Under both forms of anti-retroviral therapies, virus could be isolated in vitro from the PBMC showing continuing low-level viral replication under suppressive therapy. Overall, these data may be useful in predicting the late emergence of drug resistance mutations via the latent integrated provirus.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasma
/
Replicação Viral
/
Leucócitos Mononucleares
/
HIV-1
/
Evolução Molecular
/
Terapia Antirretroviral de Alta Atividade
/
Farmacorresistência Viral
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Curr HIV Res
Assunto da revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Austrália