Nuevas etapas y nuevas esperanzas en el tratamiento de HIV

Fil: Benetucci, Jorge A.Universidad de Buenos Aires. Facultad de Medicina; ArgentinaDesde los primeros años de la epidemia en la década del 80 hasta la actualidad hubo progresos en el conocimiento del virus y avances en la terapéutica de esta afección. Fueron de tal importancia que lograron transformar una enfermedad casi inevitablemente mortal en una patología con una tendencia creciente a la cronicidad. Todavía es necesario avanzar en el campo del diagnóstico precoz, el acceso irrestricto a los tratamientos y el desarrollo de una vacuna preventiva que permita la eventual erradicación de la pandemia

HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations

BACKGROUND: Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naive HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. CONCLUSIONS: Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate

Herpesvirus-like DNA in AIDS Kaposi’s Sarcoma in Argentina [Letter to the Editor]

First paragraph: Recently, Chang et al., using a new molecular biology technique termed Representational Difference Analysis, found herpesvirus-like DNA (KSHV) in AIDS patients with Kaposi’s sarcoma (KS). The presence of KSHV DNA sequences suggests that a new human herpesvirus may be associated with KS. The 5′ end of the 1853-bp flanking region of KSHV (nucleotides 1 to 607) was found to have 66 and 67% homologies to the corresponding regions of the major capsid protein gene of Herpesvirus Saimiri (ORF25) and Epstein Barr virus (BcLF1), respectively, both members of the gammaherpesvirus family. This finding is an important breakthrough, because a sexually transmitted agent was suspected to cause KS. The putative virus was also detected in classical KS and in African endemic KS found in young black individuals from sub-Saharan regions. KSHV sequences have also been identified in KS tissues from Taiwanese and French patients

Kinetics of HIV-1 in Cerebrospinal Fluid and Plasma in Cryptococcal Meningitis

In order to determine HIV-1 kinetics in cerebrospinal fluid (CSF) and plasma in patients with cryptococcal meningitis (CM), we undertook a prospective collection of paired CSF/plasma samples from antiretroviral therapy- free HIV-infected patients with CM. Samples were obtained at baseline (S1) and at the second (S2) and third (S3) weeks of antifungal therapy. HIV-1 CSF concentrations were significantly lower in both S2 and S3 with respect to S1. Plasma concentrations remained stable. HIV-1 concentrations were higher in plasma than CSF in all cases. Patients who survived the episode of CM (but not those who died) showed a decrease in CSF viral load, what suggests different viral kinetics of HIV-1 in the CSF according to the clinical course of this opportunistic disease