Non-AIDS-defining malignancies were more common in this cohort than AIDS-defining malignancies. This analysis provides further evidence against the use of CD4 T-cell-guided ART because of a higher risk of AIDS-defining malignancies in addition to opportunistic infections and deaths.

Experimental autoimmune orchitis (EAO) was induced in adult Wistar rats by active immunization with a testicular homogenate (TH) and adjuvants. Fifty per cent of the immunized rats developed EAO. Testicular damage became evident at 50 days after the primary immunization and increased in severity at 80 days. Phenotypic characterization of T-cell subsets (CD4+ and CD8+) and Ia+ cells was performed on cryostat sections of testis obtained from normal rats, rats immunized with adjuvant (control group) and rats immunized with TH and adjuvants (experimental group) at 50 and 80 days. Labelled cells were only detected in the interstitial area; no labelled cells were observed inside the seminiferous tubules with any of the monoclonal antibodies used (W3/25, OX-8, OX-6). A significant increase in the numbers of CD4+ and CD8+, as well as of Ia+ cells, were observed in the testis of rats with severe EAO at 80 days after the first immunization. Rats of the same experimental group without testicular damage showed no major differences compared to rats from the control group, with the exception of a lower number of CD8+ cells. Variations in the lymphocyte subsets in lymph nodes draining the site of immunization showed the opposite pattern to that observed in the testis. In conclusion, these data suggest the traffic of specifically sensitized lymphocytes from lymph nodes to the testis and an active role of CD4+, CD8+ and Ia+ cells in the pathogenesis of EAO in the rat.

To perform a diversity surveillance study we characterized viral subtypes among newly diagnosed individuals in Buenos Aires city. Plasma samples were collected from 322 drug-naive newly diagnosed HIV-1 individuals attending two voluntary counseling and testing centers. Sequences of pol and vpu genes were obtained from 283 samples and viral subtype was characterized by Neighbor-joining trees and Bootscanning analysis. BF recombinants were found in 56.9% followed by subtype B strains (39.2%). CRF12_BF structure was found in 27% of BF while another 27% had that structure only in one of both genes analyzed. Unusual non-B-non-BF strains were found in 3.9% (11/283). They were further analyzed by database searching and maximum likelihood trees in order to track their origin. Two subtype C sequences were found to be related to South American isolates while another two subtype C sequences and the subtype C segment of a BC recombinant were found to be related to isolates from Senegal. We also identified the CRF16_A2D previously found in Argentina and the CRF06_cpx commonly prevalent in Africa. The B segment of a BD recombinant was also found to be related to the Argentinean Bs suggesting a recombination between an African and a local strain. We also found a BK and two BA recombinants. In conclusion, CRF16_A2D and a new line of subtype C (of Senegalese origin) seem to be successfully established and are now spreading in Buenos Aires. BF recombinants keep recombining with local strains losing the CRF12_BF structure. Altogether they are changing the diversity of HIV in Argentina.

IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.