RESUMO
BACKGROUND: Infection with primary drug-resistant human immunodeficiency virus type 1 (HIV-1) has been associated with higher CD4(+) T cell counts in drug-naive patients, suggesting that altered viral pol replication capacity (RC) associated with drug resistance diminishes immune injury in vivo, independent of exposure to drugs. METHODS: Virus replication over a single cycle was measured by use of a viral test vector containing patient-derived HIV-1 protease and reverse transcriptase gene segments. RESULTS: Among 191 recently infected patients, pol RC ranged widely, with only 6% of the variance explained by drug-resistance mutations. Patients infected with a virus with a low pol RC (
Assuntos
Produtos do Gene pol/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Replicação Viral , Adulto , Fármacos Anti-HIV/farmacologia , Contagem de Linfócito CD4 , Farmacorresistência Viral/genética , Feminino , HIV-1/efeitos dos fármacos , HIV-1/patogenicidade , Humanos , Masculino , RNA Viral/sangue , VirulênciaRESUMO
The initial virus strains from as many as 12% of individuals with primary human immunodeficiency virus (HIV) infection have a 50% inhibitory concentration
Assuntos
Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , HIV-1/genética , HIV-1/fisiologia , Polimorfismo Genético/genética , Replicação Viral/efeitos dos fármacos , Árvores de Decisões , Farmacorresistência Viral/genética , Feminino , Produtos do Gene gag/genética , Infecções por HIV/tratamento farmacológico , Protease de HIV/genética , Inibidores da Protease de HIV/uso terapêutico , HIV-1/classificação , HIV-1/enzimologia , Humanos , Masculino , Dados de Sequência Molecular , Reprodutibilidade dos Testes , Ritonavir/farmacologia , Ritonavir/uso terapêutico , Estimulação QuímicaRESUMO
Mechanisms that underly discordant CD4+ cell/virus load (VL) responses in patients who receive highly active antiretroviral therapy (HAART) were studied in 30 human immunodeficiency virus (HIV)-positive patients, in 3 groups. Discordant responders maintained CD4+ cell levels >200/mm(3) with stable or increasing trend, despite sustained VLs of 500-5000 copies/mL, for >2 years. Treatment-success patients had CD4+ cell counts >200/mm(3) with stable or increasing trend and VLs <50 copies/mL, for >2 years. Treatment-failure patients initially responded to HAART, followed by decreasing CD4+ cell counts and increasing VLs. Interferon-gamma production to gag and noncytolytic CD8+ cell suppressive activity were greater in discordant responders. Cellular activation was greatest in patients with treatment failure. All discordant responders had non-syncytium-inducing (CCR5-tropic) viruses. Viruses from discordant responders and from patients with treatment failure had extensive resistance mutations; discordant responders had significantly lower viral replication capacities. These findings suggest that discordant responses may be related to enhanced HIV-directed immune responses, diminished cellular activation, decreased viral replication capacity, and preservation of non-syncytium-inducing virus strains.