The Duffy antigen receptor for chemokines null promoter variant does not influence HIV-1 acquisition or disease progression.

Ma’am – We read with great interest the article by He et al. [2008] describing the effects on HIV acquisition and disease progression of a single-nucleotide polymorphism (SNP, rs2814778, -46T→C) that disrupts the promoter region of the Duffy antigen receptor for chemokines (DARC) gene and abolishes gene expression in red blood cells. He et al. reported that HIV-infected African Americans have a frequency of the null homozygous genotype (-46C/C) of 70% while non-HIV infected individuals have a null genotype frequency of 60%. Based on this frequency difference they argued that the null allele confers susceptibility to infection with HIV-1. They also reported that the null genotype is associated with better outcomes amongst those who do become infected, including longer survival, slower loss of CD4(+) T-lymphocytes, and delayed progression to HIV-associated dementia

Severe renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapy.

BACKGROUND: We sought to investigate renal function in previously untreated symptomatic human immunodeficiency virus (HIV)-infected adults with CD4(+) cell counts of or =60 but or =30 but <60 mL/min/1.73 m(2)) impairments in eGFR. First-line ART regimens included zidovudine-lamivudine plus tenofovir disoproxil fumarate (for 74% of patients), nevirapine (16%), and abacavir (9%) (mostly nonrandomized allocation). After ART initiation, the median eGFR was 89-91 mL/min/1.73 m(2) for the period from week 4 through week 96. Fifty-two participants (1.6%) developed severe reductions in eGFR by week 96; there was no statistically significant difference between these patients and others with respect to first-line ART regimen received (P = .94). Lower baseline eGFR or hemoglobin level, lower body mass index, younger age, higher baseline CD4(+) cell count, and female sex were associated with greater increases in eGFR over baseline, with small but statistically significant differences between regimens (P < .001 for all). CONCLUSIONS: Despite screening, mild-to-moderate baseline renal impairment was relatively common, but these participants had greatest increases in eGFR after starting ART. Severe eGFR impairment was infrequent regardless of ART regimen and was generally related to intercurrent disease. Differences between ART regimens with respect to changes in eGFR through 96 weeks were of marginal clinical relevance, but investigating longer-term nephrotoxicity remains important

An Evaluation of HIV Elite Controller Definitions within a Large Seroconverter Cohort Collaboration

for C A S C A D E Collaboration in EuroCoordInternational audienceBackground: Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype.Methods: We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve).Results: Most definitions classify ∼1% as ECs with median HIV-RNA 43–903 copies/ml and median CD4>500 cells/mm3. Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements 90% of measurements <400 copies/ml over ≥10 years be used to define this phenotype

Fowlpoxvirus recombinants coding for the CIITA gene increase the expression of endogenous MHC-II and Fowlpox Gag/Pro and Env SIV transgenes

A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+T cells. In this context, the class II transactivator (CIITA) has a pivotal role in triggering the adaptive immune response through induction of the expression of class-II major histocompatibility complex molecule (MHC-II), that can present antigens to CD4+T helper cells. Here, we report on construction of novel FPgp and FPenv recombinants that express the highly immunogenic SIV Gag-pro and Env structural antigens. Several FP-based recombinants, with single or dual genes, were also developed that express CIITA, driven from H6 or SP promoters. These recombinants were used to infect CEF and Vero cells in vitro and determine transgene expression, which was evaluated by real-time PCR and Western blotting. Subcellular localisation of the different proteins was evaluated by confocal microscopy, whereas HLA-DR or MHC-II expression was measured by flow cytometry. Fowlpox recombinants were also used to infect syngeneic T/SA tumour cells, then injected into Balb/c mice to elicit MHC-II immune response and define the presentation of the SIV transgene products in the presence or absence of FPCIITA. Antibodies to Env were measured by ELISA. Our data show that the H6 promoter was more efficient than SP to drive CIITA expression and that CIITA can enhance the levels of the gag/pro and env gene products only when infection is performed by FP single recombinants. Also, CIITA expression is higher when carried by FP single recombinants than when combined with FPgp or FPenv constructs and can induce HLA-DR cell surface expression. However, in-vivo experiments did not show any significant increase in the humoral response. As CIITA already proved to elicit immunogenicity by improving antigen presentation, further in-vivo experiments should be performed to increase the immune responses. The use of prime/boost immunisation protocols and the oral administration route of the recombinants may enhance the immunogenicity of Env peptides presented by MHC-II and provide CD4+T-cell stimulation