Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Rifamicinas/farmacologia , Linfócitos T/efeitos dos fármacos , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Resistência a Múltiplos Medicamentos , Feminino , Citometria de Fluxo , Humanos , Masculino , Rifamicinas/uso terapêutico , Linfócitos T/metabolismoRESUMO
OBJECTIVE: We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1). DESIGN: CD4 cell lines were infected with laboratory strains and peripheral blood mononuclear cells were infected with primary isolates for evaluation of the anti-HIV effects. Peripheral blood lymphocytes were evaluated for of P-gp and MRP1 functions. METHODS: HIV replication was assessed by enzyme-linked immunosorbent assay. HIV glycosylation was measured by metabolic labeling of viral particles with [H] glucosamine. Synergism was tested using isobolograms. P-gp and MRP1 functions were assayed using rhodamine 123 (Rh123) and carboxyfluorescein (CF) efflux assays, respectively. RESULTS: CQ alone inhibited HIV replication and glycosylation in a dose-dependent manner. In combination with indinavir (IDV), ritonavir, or saquinavir (SQV), CQ had a synergistic effect at concentrations found in plasma of subjects receiving malaria prophylaxis. CQ decreased the 50% effective concentration of IDV in primary isolates from Africa and restored the response to IDV or SQV in 3 PI-resistant isolates. CQ increased the block of Rh123 and CF efflux activity exerted by PIs. CONCLUSION: The inhibitory effects of CQ on HIV glycosylation are associated with synergistic effects in combination with PIs. The CQ/PI combination exerts combined inhibitory effects on P-gp and MRP1 function.