BackgroundNone of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs.MethodsTo overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1.ResultsOur approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4+ and CD8+ T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4+ and CD8+ T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ+ CD8+ T cells being Granzyme B+ and able to degranulate (CD107a+).ConclusionsThese data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0392-5) contains supplementary material, which is available to authorized users.
BackgroundEarly diagnosis of HIV infection can prevent morbidity and mortality as well as reduce HIV transmission. The aim of the present study was to assess prevalence, describe trends and identify factors associated with late presentation of HIV infection in Barcelona (Spain) during the period 2001-09.MethodsDemographic and epidemiological characteristics of cases reported to the Barcelona HIV surveillance system were analysed. Late presentation was defined for individuals with a CD4 count below 350 cells/ml upon HIV diagnosis or diagnosis of AIDS within 3 months of HIV diagnosis. Multivariate logistic regression were used to identify predictors of late presentation.ResultsOf the 2,938 newly diagnosed HIV-infected individuals, 2,507 (85,3%) had either a CD4 cell count or an AIDS diagnosis available. A total of 1,139 (55.6%) of the 2,507 studied cases over these nine years were late presenters varying from 48% among men who have sex with men to 70% among heterosexual men. The proportion of late presentation was 62.7% in 2001-2003, 51.9% in 2004-2005, 52.6% in 2006-2007 and 52.1% in 2008-2009. A decrease over time only was observed between 2001-2003 and 2004-2005 (p = 0.001) but remained constant thereafter (p = 0.9). Independent risk factors for late presentation were older age at diagnosis (p < 0.0001), use of injected drugs by men (p < 0.0001), being a heterosexual men (p < 0.0001), and being born in South America (p < 0.0001) or sub-Saharan Africa (p = 0.002).ConclusionLate presentation of HIV is still too frequent in all transmission groups in spite of a strong commitment with HIV prevention in our city. It is necessary to develop interventions that increase HIV testing and facilitate earlier entry into HIV care.
The prison population is a high-risk group for tuberculosis (TB). This investigation aimed to study predictive factors of treatment adherence among prisoners involved in a pilot programme of supervised treatment. The study included TB patients from the Men's Penitentiary Center of Barcelona (MPCB) in 1995. Directly observed therapy (DOT) was carried out in the infirmary or in a methadone programme. Released prisoners were referred to the municipal maintenance methadone programmes (MMP) and other social resources. Incentives and enablers were used to improve compliance (economic aid for nutritional and housing needs, methadone programmes and admittance to a sociosanitary centre). The outcome of the patients' adherence was classified as follows: completed, defaulted, dead or transferred out. Factors associated with adherence were investigated through logistic regression. The programme included 62 patients, 43 of whom were intravenous drug users (IVDU) and 46 were infected with the human immunodeficiency virus (HIV). Nineteen had previously had TB and 32 were released from prison during TB treatment. Overall adherence was 89%; 97% among those who completed treatment in prison, and 79% among those who completed treatment outside prison (p=0.05). Ninety-five per cent of IVDU in an MMP completed treatment. Homeless or alcoholic exprisoners completed treatment only if they were admitted to sociosanitary centres. DOT throughout treatment resulted in better adherence (odds ratio (OR)= 16.80; confidence interval (CI): 2.42-116.2)). Those who were incarcerated throughout treatment also showed better adherence (OR= 7.36; CI: 0.79-48.16). Antituberculosis treatment adherence in prisoners was high even after release with adequate co-ordination among intrapenitentiary and extrapenitentiary programmes. Maintenance methadone programmes proved very useful in intravenous drug users, as did admittance to sociosanitary centres for indigent or alcoholic exprisoners undergoing treatment.
Purpose: The Prevalhep study seeks to determine the prevalence of factors associated with hepatitis C virus (HCV) and B (HBV) in Spanish prisoners Methods: Observational, cross-sectional study which randomly selected 18 Spanish prisons to participate, and with 21 prisoners/CentreResults: There were 378 prisoners selected, 370 of whom had serological HCV and 342 had VHB data. The HCV population were predominantly male (91.6%), of middle age (66.7% contact status with HBV (HBcAb+ and/or HBsAg+), while 37.5% were susceptible to HB. Conclusions:The prevalence of HBV and HCV has decreased in the Spanish prison population, probably as a result of decrease in IDU transmission, and an increase in immigrant prisoner population that does not have this risk behaviour.[Word count = 198]
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