Impact of raltegravir on HIV-1 RNA and DNA forms following initiation of antiretroviral therapy in treatment-naive patients.
J Antimicrob Chemother
; 69(10): 2809-18, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24962031
ABSTRACT
OBJECTIVES:
The rapid early-phase decay of plasma HIV-1 RNA during integrase inhibitor-based therapy is not fully understood. The accumulation of biologically active episomal HIV-1 cDNAs, following aborted integration, could contribute to antiviral potency in vivo.METHODS:
This prospective, controlled clinical observation study explored raltegravir's impact on the dynamics of HIV-1 RNA in plasma, and concentrations of total HIV-1 cDNA, episomal 2-long terminal repeat (LTR) circles and HIV-1 integrants in peripheral blood mononuclear cells (PBMC). Individuals starting therapy with two nucleoside reverse transcriptase inhibitors plus either raltegravir (raltegravir group; nâ=â10 patients) or boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitor (control group; nâ=â10 patients) were followed for 48 weeks.RESULTS:
Suppression of HIV-1 RNA (<50 copies/mL) was reached earlier (5/10 versus 0/10 at week 4; 8/10 versus 4/10 at week 12) on raltegravir. Significant total HIV-1 cDNA reductions in PBMC were reached by day 99 and persisted until day 330, with median factors of decrease of 7.2 and 8.9, respectively. Broad inter-individual variations, yet no treatment-associated differences, were noted for HIV-1 cDNA concentrations. Despite reductions in HIV-1 RNA (â¼3 log) and total HIV-1 cDNA (â¼1 log), concentrations of integrants and 2-LTR circles remained largely unchanged.CONCLUSIONS:
These results extend the previously reported early benefit of raltegravir on the decline of plasma viraemia to treatment-naive patients. The modest treatment-associated, yet group-independent, decline in total HIV-1 cDNA load and the lack of significant changes in integrated and episomal HIV-1 cDNA suggest that most integrated DNA is archival and targeting of HIV reservoirs other than PBMC may underlie beneficial effects of raltegravir.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinonas
/
Infecções por HIV
/
HIV-1
/
Inibidores de Integrase de HIV
Limite:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article