HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil.

The transactivator of transcription (Tat) is a key HIV regulatory protein. We aimed to identify the frequency of key polymorphisms in HIV-1C compared with HIV-1B Tat protein, chiefly in the cysteine-, arginine-, and glutamine-rich domains and identify novel point mutations in HIV-1B and C sequences from Southern Brazil. This study was the first to investigate the genetic diversity and point mutations within HIV-1 Tat C in a Brazilian cohort. This was an observational, cross-sectional study, which included sequences of HIV-1B (n = 20) and HIV-1C (n = 21) from Southern Brazil. Additionally, 344 HIV-1C sequences were obtained from the Los Alamos database: 29 from Brazil and 315 from Africa, Asia, and Europe. The frequency of C31S substitution on HIV-1 Tat C in Brazil was 82% vs. 10% in the HIV-1B group (p < 0.0001). The frequency of the R57S substitution among the HIV-1C sequences from Brazil was 74% vs. 20% in HIV-1B (p = 0.004), and that of substitution Q63E in HIV-1C was 80% and 20% in HIV-1B (p < 0.0001). The mutation P60Q was more frequent in HIV-1B than in HIV-1C (55% and 6.12%, respectively, p < 0.0001)). Novel point mutations in the HIV-1C and B Tat functional domains were described. The frequency of C31S and other key point mutations in HIV-1 Tat C in Brazil were similar to those described in Africa, although lower than those in India. The Tat-B and C sequences found in Southern Brazil are consistent with biological differences and have potential implications for HIV-1 subtype pathogenesis.

Detection and quantification of human immunodeficiency virus and hepatitis C virus in cadaveric tissue donors using different molecular tests.

BACKGROUND: Tissues from cadaveric donors are used in several clinical circumstances, and the transmission of infectious diseases has been reported. Cadaveric donor (CD) blood sample analysis is challenging due to its poor quality. However, studies have demonstrated the usefulness of molecular based methods, and the lack of studies using available commercial molecular tests was reported. OBJECTIVE: The aim of this study was to evaluate the performance, specificity, sensitivity, and accuracy of different commercial molecular tests for HIV and HCV detection and quantification in CD through spiked samples. STUDY DESIGN: 20 CD and 20 blood donor samples were tested using 1,000 copies/mL and 1,000 IU/mL of lyophilized standards of HIV and HCV, respectively. Samples were analyzed by different molecular kits: XPERT HCV Viral Load and HIV-1 (Cepheid), COBAS® TaqMan® HIV-1 and COBAS® TaqMan® HCV Test, v2.0 (Roche), and artus® HI Virus-1 QS-RGQ and artus® HCV RG RT-PCR Kit (Qiagen). RESULTS: HIV and HCV in CD were detected by RT-PCR-based quantitative kits. The tests performed by the Cepheid and the Roche kits showed the most accurate, sensitive and specific results, however, a wide variability between the assays and kits was observed. The Qiagen kits did not demonstrate satisfactory results. CONCLUSIONS: CD evaluation showed great variability. The Cepheid and Roche kits were more sensitive for detecting HIV on CD and Cepheid was the most efficient kit for HCV quantification in CD. The Roche and Cepheid kits can be used to screen tissue donors for HIV and HCV.

Host Factor Predictors in Long-term Nonprogressors HIV-1 Infected with Distinct Viral Clades.

BACKGROUND: HIV-1+ long-term nonprogressors (LTNPs) maintain natural control of viral infection. This study sought to identify and characterize HIV- LTNPs series case, regarding the presence of possible host factors that may be associated with this status. METHODS: We evaluated the plasma levels of IP-10/IL-8 chemokines, HLA-B alleles, and IL28B rs12979860 polymorphism in 24 LTNPs who presented with infection by different clades of HIV-1. RESULTS: IL-8 chemokine was significantly higher in progressors than in LTNPs, but there was no difference between the LTNP subgroups. There was a negative correlation in CD4+ T cell (TC) count and IL-8 dosage, and a positive correlation with CD8+ TC. IP-10 chemokine levels were associated with viremia, and the elite controller (EC) subgroup showed nearly the same level than healthy individuals and progressors with viral load suppressed. Furthermore, the CD4+ TC count, percentage of CD4+ TC, and CD4/CD8 ratio were negatively correlated with IP-10. No association was found in plasma levels of IL-8 and IP-10 chemokines and HIV-1 clades. In the EC/viremic controller subgroup, 80% presented with at least one HLA-B allele previously considered as potentially protective for AIDS progression. No association was observed between the HLA-B alleles and HIV- 1 clades. The IL28B CC genotype was identified in 87.5% of LTNPs. CONCLUSION: In this LTNP series case we observed different host factors that may be contributing to their nonprogressor status, and the association of these factors with the control of infection progression may be critically important for future therapeutic and prophylactic options in HIV-1 infection.