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

Detection of HIV-1 dual infections in highly exposed treated patients

<p>Abstract</p> <p>Background</p> <p>Genetic characterization of HIV-1 in Argentina has shown that BF recombinants predominate among heterosexuals and injecting drug users, while in men who have sex with men the most prevalent form is subtype B.</p> <p>Objectives</p> <p>The aim of this work was to investigate the presence of HIV dual infections in HIV-infected individuals with high probability of reinfection</p> <p>Study design</p> <p>Blood samples were collected from 23 HIV positive patients with the risk of reinfection from Buenos Aires. A fragment of the HIV gene <it>pol </it>was amplified and phylogenetic analyses were performed. Antiretroviral drug resistance patterns of all the sequences were analyzed.</p> <p>Results</p> <p>Five dual infections were detected with four patients coinfected with subtype B and BF recombinants and one patient was coinfected with two BF recombinants presenting different recombination patterns. Prolonged infection with a stable clinical condition was observed in the five individuals. Resistance mutation patterns were different between the predominant and the minority strains.</p> <p>Conclusions</p> <p>Our results show that HIV dual infection can occur with closely related subtypes, and even with different variants of the same recombinant form in certain populations. Clinical observations showed neither aggressive disease progression nor impact on the resistance patterns in the dually-infected patients.</p

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

HUMAN HERPESVIRUS 8 CAN BE TRANSMITTED THROUGH BLOOD IN DRUG ADDICTS

Human Herpes virus type-8 (HHV-8) seroprevalence was studied in a population of HIV positive intravenous drug users (IVDUs) from Argentina. Analysis of this population also indirectly made it possible to study HHV-8 blood transmission, because these individuals frequently engage in needle sharing behavior and are capable of acquiring a broad array of blood borne pathogens, including Hepatitis B/C virus. The seroprevalence of HHV-8 in IVDUs was compared to a group of non-IVDUs and HIV negative individuals. Of the 223 individuals tested, 13.45% were HHV-8 positive, 16.99% in the IVDUs group, and 5.71% in the non-IVDUs. Among HIV positive IVDUs, 25/144 (17.36%) were also HHV-8 seropositive. The seropositivity rate of HHV-8 in HIV negative IVDUs was 11.1%. In contrast, HHV-8 seroprevalence in HIV negative heterosexual individuals without drug usage behavior was even lower (5.71%). The rate of HHV-8 infection in HIV positive IVDUs was three times as high compared to the non IVDU HIV negative individuals, suggesting that IVDU is a risk for HHV-8 infection. Furthermore, it was found that IVDUs showed a very high rate of Hepatitis B/C (52.77%), which also correlate with HHV-8 infection in this population (23.68%). All Hepatitis B/C positive individuals were also HIV positive. Our data confirm other studies showing that individuals who share needles are at risk for acquiring Hepatitis B/C and HIV infections. In addition, our results suggest that they are also at risk to acquiring HHV-8 infection by the same route

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