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It is believed that initial encounter between HIV and the human host triggers a complex series of events that dictate future disease course. Inter-individual differences among the host-players involved in these processes seem to early determine different rates of disease progression. Here we were aimed at studying the relationship between innate and adaptive soluble immune mediators, HIV-specific T-cell response and the course of acute infection. Methods Plasma levels of 37 cytokines were measured by Luminex technology in different groups of volunteers: 10 healthy donors (HD) and 50 HIV infected-subjects: 10 chronics, 12 aviremic controllers (EC) and 28 subjects enrolled during acute infection (AI). All HIV patients were offHAART. Frozen PBMCs from the same individuals were used to determine HIV-specific T-cell responses by IFNgamma ELISPOT. Data was compared inter- and intragroups and correlated to viral load (VL), CD4 T cell counts and both virological (VL) and immunological (CD4 count) set-points (in AI), using parametric and non-parametric statistics. Results Compared to HD, cytokines significantly elevated during acute and chronic infection included IL-1alfa, IL-10, IP-10 and TNF-alfa. Conversely, IL-12p40 and the macrophagederived chemokine (MDC) were only significantly elevated in chronics and not in AI subjects who showed similar levels to HD and even EC. Moreover, levels of IL-12p40, IL-12p70 and MDC directly correlated with CD4 T-cell count among chronics and both CD4 T-cell count and immunological set point in AI. Regarding HIV-specific T-cell response during AI, proportion of Gag-specific and Nef-specific cells significantly correlated (directly and inversely, respectively) with immunological set point. Conclusion Both early and late components of the immune system help preserve CD4 T-cell subset in HIV+ subjects: key cytokines involved in the initiation and regulation of cellular immune response and anti-Gag specificity of effector T-cells. These features should be taken into account during vaccine formulation design to boost favorable results.

Background Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial. Methods Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients. Results Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively. Conclusions In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression.

Background The immune response of HIV-infected individuals shapes the evolution of the virus by selecting escape mutation. After transmission to a new host, the HLA-mediated immune pressure changes. The objective of our study was to characterize the dynamics of HLA-anchor escape mutations after transmission. Methods We studied 6 transmission events between members of serodiscordant couples collecting blood samples from the donor and the previously seronegative-partner at the moment of seroconversion, and a second sample at least 6 months post-infection. HLA-I typing was performed by the SSOP-PCR method. The viral gene gag was amplified by RT-PCR and cloned into the pGEM-T vector for viral quasiespecies analysis. Transmitted strain was identified by phylogenetic analysis. Escape mutation was defined as viral polimorphisms located in HLA-anchor position that eliminate an epitope predicted by the NetMHC (CBS Prediction Server). Significant variations in the number

Background: Multiple HIV-1 intersubtype recombinants have been identified in human populations. Previous studies from our lab group have shown that the epidemic in Argentina is characterized by the high prevalence of a circulating recombinant form, CRF12_BF, and many related BF recombinant forms. In these genomic structures a recombination breakpoint frequently involved the vpu coding region. Due to the scarce knowledge of Vpu participation in the virion release process and its impact on pathogenesis and of the functional capacities of intersubtype recombinant Vpu proteins, the aim of this work was to perform a comparative analysis on virion release capacity and relative replication capacity among viral variants harboring either a BF recombinant Vpu or a subtype B Vpu. Results: Our results showed that BF recombinant Vpu was associated to an increased viral particles production when compared to WT B variant in tetherin-expressing cell lines. This observation was tested in the context of a competition assay between the above mentioned variants. The results showed that the replication of the BF Vpu-harboring variant was more efficient in cell cultures than subtype B, reaching a higher frequency in the viral population in a short period of time. Conclusion: This study showed that as a result of intersubtype recombination, a structurally re-organized HIV-1 Vpu has an improved in vitro capacity of enhancing viral replication, and provides evidence of the changes occurring in this protein function that could play an important role in the successful spread of intersubtype recombinant variants. Fil: de Candia, Cristian Ariel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia Para El Sida; Argentina Fil: Espada, Constanza Eleonora. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia Para El Sida; Argentina Fil: Duette, Gabriel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ghiglione, Yanina Alexandra. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Turk, Gabriela Julia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Salomon, Horacio Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Carobene, Mauricio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Methods We studied 65 HIV-positive patients whose HLA-A and -B genes were previously typed by SSOP technique. We setup a sequence-based typing of the most prevalent alleles in Oran. HLA-A and B were initially PCR-amplified and exons-2 and -3 were sequenced. NCBI-SBT-Interpretation tool was used to confirm the two-digits typing with previous SSOP data. We designed a set of primers specifics for HLAs highly prevalent in Oran to achieve differential PCR-amplification of each allele in heterozygote patients. Phylogenetic analysis was used to assign exons-2 and -3 sequences to a high-resolution HLA group.