Viral load and disease progression as responsible for endothelial activation and/or injury in human immunodeficiency virus-1-infected patients.

The endothelium participates in haemostasis, inflammation, blood pressure regulation and other physiological systems. Consequently, endothelial dysfunction has been related to hypertension, thrombosis and atherosclerosis. Both von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA) are synthesized by the endothelium and their plasma levels increased during endothelium activation or injury. So far, they are well-known markers of endothelial cell function. Many circumstances activate or damage the endothelium, such as viruses, bacterium and inflammation. Circulating vWF and t-PA were studied in 92 unselected human immunodeficiency virus-1 (HIV-1)-infected patients [27 patients with and 65 patients without acquired immunodeficiency syndrome (AIDS)] and correlated with plasma levels of pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-6), viral load, CD4 T-cell count and infectious status. HIV-1-infected patients had significantly higher plasma levels of vWF (152 versus 90%), tumour necrosis factor-alpha (31.3 versus 9.0 pg/ml) and interleukin-6 (3.5 versus 1.9 pg/ml) but not t-PA (5.9 versus 4.2 ng/ml) than the control group. These two endothelial markers correlated significantly with viral load and interleukin-6 levels in HIV-1-infected patients. The highest levels of vWF and t-PA were found in patients with AIDS. In conclusion, endothelial cell perturbation is present in HIV infection and may be a consequence of different mechanisms such as viral load, cytokines and advanced diseases.

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-naïve 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.

Update on primary HIV-1 resistance in Argentina: emergence of mutations conferring high-level resistance to nonnucleoside reverse transcriptase inhibitors in drug-naive patients.

Here we present a survey including 52 drug-naive recently HIV-1-infected subjects from Buenos Aires City and province (79%) and 3 other regions in Argentina (21%). Recent infections were established from previous negative serology (32/52), indeterminate Western blot (12/52), or acute retroviral syndrome after high-risk HIV exposure (8/52) within 9 months before genotyping (median time, 4.2 months). Genotyping was performed from plasma by sequencing both protease and reverse transcriptase. Phylogenetic analysis combined with bootscanning resulted in 21 subtype B sequences and 31 B/F recombinants (RecBF). On protease, minor resistance-related mutations were found in both subtype B and RecBF with low frequencies. The substitution L89M, recently suggested as a resistance-related mutation in some subtype F viruses, was observed in 1 RecBF. On reverse transcriptase, major resistance-related mutations were found in 4 of 52 (7.7%) patients from different health centers: M41L (subtype B) and K103N+/-P225H (1 RecBF and 2 subtype B). The greater than 5% resistance threshold found indicates a need for sentinel resistance surveillances calling for an update in the current resistance testing guidelines in Argentina.

Infecciones y otros problemas de salud en usuarios de pasta base de cocaina en un centro asistencial de Buenos Aires, Argentina / Infections and other health problems among coca paste users at a drug treatment center in Buenos Aires, Argentina

INTRODUCCIÓN: la pasta base de cocaína (PBC) es una forma fumable de cocaína de creciente utilización entre los jóvenes. OBJETIVO: describir el patrón de consumo de drogas, las seroprevalencias de VIH, hepatitis B (VHB), hepatitis C (VHC), sífilis y otrosproblemas de salud en usuarios de PBC en un centro asistencial de Argentina. MÉTODO: se incluyeron voluntarios mayores de 18 años, asistidos en el Centro Nacional de Reeducación Social (CENARESO)en el período 2006-2007, que consumieron PBC en los 6 meses anteriores a la entrevista y que nunca utilizaron drogas inyectables. Se aplicó un cuestionario estructurado, se tomó una muestra de sangre para serología de VIH, VHB, VHC y sífilis, y se analizó una sub-muestra de radiografías de tórax. RESULTADOS: más de la mitad de los 146 voluntarios manifestó haber fumado PBC varias veces por semana. Los participantes eran también consumidores frecuentes de cocaína en polvo (64%), cannabis (80,8%) y tranquilizantes (44,5%). Los principales problemas de salud auto-percibidos como consecuencia del consumo de PBC fueron las lesiones orales y la pérdida de peso. El 4,3% de los voluntarios resultó VIH-positivo. Las prevalencias de infección por sífilis, VHB y VHC fueron 2,7%, 5,5%, y 5,5%, respectivamente. El 16% estaba coinfectado con uno o más de los agentes estudiados. DISCUSIÓN: la prevalencia de infecciones, unida a otros problemas de salud de los usuarios de PBC, indica la necesidad de nuevas investigaciones a fin de diseñar intervenciones preventivas y terapéuticas apropiadas

INTRODUCTION: cocaine paste is a smokable form of cocaine increasingly used among young people. OBJECTIVE:to describe patterns of drugs, seroprevalences of HIV, hepatitis B (HBV), hepatitis C (HCV), syphilis and other health problems among coca paste users assisted at a drug treatment center in Argentina. METHOD: volunteers, eighteen-year-old and olderassisted at the National Center for Social Re-education (CENARESO)during 2006-2007, who had consumed coca paste over the past 6 months previous to the interview and had never injected drugs, were selected. A structured questionnaire wasused and blood was drawn to test HIV, HBV, HCV and syphilis. A sub-sample of thorax X-rays was analyzed. RESULTS: morethan half of the 146 volunteers had smoked coca paste severaltimes a week. The use of other drugs was frequently associated: sniffed cocaine 64%, cannabis 80,8%, and tranquilizers 44,5. Oral lesions and lost of weight were referred as health problems stemming from coca paste use. Out of the 146 volunteers, 4.3%resulted HIV-positive. Prevalences of infection for syphilis, HBV, and HCV were 2,7%, 5,5% and 5,5%, respectively. 16% wasco-infected with one or more infectious agents. DISCUSSION: the prevalence of infections detected, along with other clinical problems found among this coca paste users, show the need for further research, in order to design proper preventive and therapeutic interventions

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 percent were HHV-8 positive, 16.99 percent in the IVDUs group, and 5.71 percent in the non-IVDUs. Among HIV positive IVDUs, 25/144 (17.36 percent) were also HHV-8 seropositive. The seropositivity rate of HHV-8 in HIV negative IVDUs was 11.1 percent. In contrast, HHV-8 seroprevalence in HIV negative heterosexual individuals without drug usage behavior was even lower (5.71 percent). 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 percent), which also correlate with HHV-8 infection in this population (23.68 percent). 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.