RESUMEN
NK cells are regulated in part by killer Ig-like receptors (KIR) that interact with HLA molecules on potential target cells. KIR and HLA loci are highly polymorphic and certain KIR/HLA combinations were found to protect against HIV disease progression. We show in this study that KIR/HLA interactions also influence resistance to HIV transmission. HIV-exposed but seronegative female sex workers in Abidjan, Côte d'Ivoire, frequently possessed inhibitory KIR genes in the absence of their cognate HLA genes: KIR2DL2/KIR2DL3 heterozygosity in the absence of HLA-C1 and KIR3DL1 homozygosity in the absence of HLA-Bw4. HIV-seropositive female sex workers were characterized by corresponding inhibitory KIR/HLA pairings: KIR2DL3 homozygosity together with HLA-C1 and a trend toward KIR3DL1/HLA-Bw4 homozygosity. Absence of ligands for inhibitory KIR could lower the threshold for NK cell activation. In addition, exposed seronegatives more frequently possessed AB KIR genotypes, which contain more activating KIR. The data support an important role for NK cells and KIR/HLA interactions in antiviral immunity.
Asunto(s)
Infecciones por VIH/inmunología , VIH-1/inmunología , Antígenos HLA/sangre , Antígenos HLA/genética , Receptores Inmunológicos/fisiología , Trabajo Sexual , Adulto , Côte d'Ivoire , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Infecciones por VIH/genética , Infecciones por VIH/transmisión , Seronegatividad para VIH/genética , Seronegatividad para VIH/inmunología , Seropositividad para VIH/genética , Seropositividad para VIH/inmunología , Antígenos de Histocompatibilidad Clase I/sangre , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Inmunidad Innata/genética , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Receptores Inmunológicos/sangre , Receptores Inmunológicos/genética , Receptores KIR , Receptores KIR2DL2 , Receptores KIR2DL3 , Receptores KIR3DL1RESUMEN
OBJECTIVE: To describe changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of HIV-2-infected patients receiving antiretroviral (ARV) therapy in Abidjan, Côte d'Ivoire. METHODS: Consecutive blood samples were collected from 18 HIV-2-infected ARV-naive patients who had received ARV therapy in the UNAIDS drug access initiative (UNAIDS-DAI) in Abidjan between August 1998 and July 2000. Changes in HIV-2 plasma viral load, CD4+ cell counts, and genotypic and phenotypic drug resistance testing were determined. RESULTS: At baseline, 11 (61%) of the 18 patients initiated highly active antiretroviral therapy (HAART) and seven (39%) received dual therapy. No significant change in median viral load was observed at 2 months (P = 0.09), at 6 months (P = 0.06), and at 12 months of therapy (P = 0.26). No significant increase in CD4+ cell counts was observed at 12 months (P = 0.10). All four patients on indinavir-containing HAART had undetectable viral loads at 2-4 months of therapy. However, none of seven patients on nelfinavir-containing HAART had a substantial decrease in viral load. Viruses from 14 patients were analyzed, 12 of which (86%) had at least one primary resistance mutation that is known to confer resistance to HIV-1 virus. Three patients had the multi-drug-resistant mutation, Q151M, two of whom showed reduced susceptibility to zidovudine, didanosine, stavudine and zalcitabine. CONCLUSION: Our limited findings show that nelfinavir-containing regimens may have limited virologic benefit to HIV-2-infected patients.