RESUMO
The mechanisms of CD4(+) T-cell count decline, the hallmark of HIV disease progression, and its relationship to elevated levels of immune activation are not fully understood. Massive depletion of CD4(+) T cells occurs during the course of HIV-1 infection, so that maintenance of adequate CD4(+) T-cell levels probably depends primarily on the capacity to renew depleted lymphocytes, that is, the lymphopoiesis. We performed here a comprehensive study of quantitative and qualitative attributes of CD34(+) hematopoietic progenitor cells directly from the blood of a large set of HIV-infected persons compared with uninfected donors, in particular the elderly. Our analyses underline a marked impairment of primary immune resources with the failure to maintain adequate lymphocyte counts. Systemic immune activation emerges as a major correlate of altered lymphopoiesis, which can be partially reversed with prolonged antiretroviral therapy. Importantly, HIV disease progression despite elite control of HIV replication or virologic success on antiretroviral treatment is associated with persistent damage to the lymphopoietic system or exhaustion of lymphopoiesis. These findings highlight the importance of primary hematopoietic resources in HIV pathogenesis and the response to antiretroviral treatments.
Assuntos
Contagem de Linfócito CD4 , Infecções por HIV/imunologia , Células-Tronco Hematopoéticas/citologia , Linfopoese/imunologia , Replicação Viral/imunologia , Adulto , Separação Celular , Progressão da Doença , Citometria de Fluxo , Infecções por HIV/virologia , HIV-1/fisiologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Pessoa de Meia-IdadeRESUMO
We evaluated the safety and efficacy of a twice daily regimen containing 400 mg of indinavir and 100 mg of ritonavir in 32 human immunodeficiency virus (HIV)-infected women during pregnancy. The median indinavir trough concentration was 208 ng/ml during the third trimester. At delivery, 26 of 28 women on indinavir-ritonavir had HIV RNA levels of <200 copies/ml. No infant was HIV infected. These data are encouraging for the use of this combination for prevention of mother-to-child transmission of HIV.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Indinavir/uso terapêutico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Indinavir/administração & dosagem , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Inibidores da Transcriptase Reversa/administração & dosagem , Ritonavir/administração & dosagem , Resultado do TratamentoRESUMO
The dynamics of mutations associated with resistance to antiretroviral drugs were analyzed after cessation of therapy. The results showed that the kinetics of the shift to wild-type amino acid residues were significantly faster for protease inhibitors, intermediate for nonnucleoside reverse transcriptase inhibitors, and slower for nucleoside reverse transcriptase inhibitors.