RESUMO
The impact of Structured Treatment Interruption (STI) in peripheral blood mononuclear cell (PBMC) proviral reservoirs in 41 highly active antiretroviral therapy (HAART)-treated viremic individuals at baseline and 12 weeks after STI was determined using quantitative PCR (qPCR). Viral load increased 0.7 log(10) and CD4 decreased 97.5 cells/mm(3) after 12 weeks. A total of 28 of the 41 individuals showed an increased proviral load, 19 with a statistically significant increase above 10%. An increase in active viral replication is an important factor in the replenishment of the proviral reservoir even for short time periods.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , DNA Viral/isolamento & purificação , Infecções por HIV/tratamento farmacológico , Provírus/isolamento & purificação , Carga Viral , Suspensão de Tratamento , Adulto , Contagem de Linfócito CD4 , Células Cultivadas , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Falha de TratamentoRESUMO
We analyzed gp120V3 HIV-1 env region genetic diversity of 27 patients failing antiretrovirals and subjected to 12-week structured treatment interruption (STI). Based on heteroduplex mobility assays, eight patients presented low pre- and post-STI genetic diversity (G1); five presented high pre-STI but low post-STI diversity (G2); five presented low pre-STI and high post-STI diversity (G3); and nine, high pre- and post-STI diversity (G4). One patient from G1, two from G2 and two from G3 were subjected to proviral DNA end-point PCR and sequencing. In three patients, the dramatic disturbance caused by STI resulted in ancestral viral progeny activation, which repopulated the cell reservoir. In two patients presenting highly homogeneous sequences and low immune selective pressure (dN/dS ratio <1), this phenomenon was not observed. The mechanisms involved in viral evolution, in which antiretroviral therapy also applies selective pressure, sometimes affects coreceptor usage of circulating viruses, leading to the suppression of x4 strains.