RESUMO
BACKGROUND: The Alere q HIV-1/2 Detect test (Alere Detect) is a rapid point-of-care (POC) nucleic acid test (NAT) that can detect and differentiate HIV-1 and HIV-2 in 25-µL whole blood or plasma samples. The Alere Detect test has been validated for early infant diagnosis of HIV-1 infection, and it is the only POC NAT device currently known to detect HIV-2, which is endemic in West Africa. OBJECTIVES: To evaluate the sensitivity detecting HIV-2 RNA and the differential performance of the Alere Detect. STUDY DESIGN: Plasma samples from non-HIV (n=4), HIV-1 (n=22), HIV-2 (n=111; 29 Group A, 2 Group B) and HIV-1/HIV-2 dually-seropositive (n=8) participants in Senegal and the United States and HIV-2 reference strains (3 Group A, 1 Group B) were tested by Alere Detect, Abbott RealTime HIV-1 and the University of Washington HIV-2 RNA quantitative (UW HIV-2) assays. RESULTS: The Alere Detect correctly differentiated between HIV-1 and HIV-2 in all 80 (100%) patient samples with detectable HIV RNA (n=20 HIV-1, 60 HIV-2). The overall HIV-2 detection concordance between Alere Detect and the UW HIV-2 assay was 68% (54/80); the concordance improved to 100% (30/30) for samples with HIV-2 RNA >300copies/mL. Neither assay detected HIV-2 RNA in 31 of 111 HIV-2 seropositive samples. CONCLUSIONS: The Alere Detect test is a novel device detecting HIV RNA in clinical samples, and differentiating HIV-1 and HIV-2 with a high level of specificity. It has the potential for use as a rapid HIV-2 NAT-based diagnosis tool in resource-limited settings and to confirm HIV-2 infection for the CDC 4th generation HIV-1/2 diagnostic algorithm.
Assuntos
Infecções por HIV/diagnóstico , HIV-2/isolamento & purificação , Sistemas Automatizados de Assistência Junto ao Leito , RNA Viral/isolamento & purificação , África Ocidental/epidemiologia , Diagnóstico Precoce , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , HIV-2/genética , Humanos , Programas de Rastreamento , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/sangue , RNA Viral/genética , Senegal/epidemiologia , Sensibilidade e Especificidade , Estados Unidos/epidemiologiaRESUMO
Contact between the human immunodeficiency virus (HIV-1) and its target cell is initiated by the interaction of viral gp120 with cellular CD4. An assembled peptide (CD4bs-M) that presents the CD4 binding site of gp120 was previously shown to inhibit the gp120-CD4 interaction. Here, we demonstrate that CD4bs-M selectively enhances infection of cells with HIV-1, whereas infection with herpes simplex virus remains largely unaffected. The effects of CD4bs-M variants containing D-amino acids, or prolines at selected positions, point to the importance of side chain orientation and spatial orientation of this fragment. Furthermore, CD4bs-M was shown to assemble into amyloid-like fibrils that capture HIV-1 particles, which likely contributes to the infection-enhancing effect. Beyond infection enhancement, CD4bs-M enabled HIV-1 infection of CD4-negative cells, suggesting that binding of the peptide to gp120 facilitates interaction of gp120 with coreceptors, which might in turn enhance HIV-1 entry.