Primer caso de sida en el hospital de enfermedades Infecciosas "Francisco J. Muñiz" / First case of aids in the "Francisco J. Muñiz" hospital for infectious diseases

Entre julio de 1979 y abril de 1981 se conocieron en Nueva York y en Los Ángeles (EEUU) los primeros casos de neumonía por Pneumocystis carinii en hombres jóvenes homosexuales previamente sanos, con importantes alteraciones de la inmunidad celular. Simultáneamente se informaron nuevos casos de enfermos con dos o más infecciones oportunistas y sarcoma de Kaposi. El sida era una nueva enfermedad cuyo agente causal, el actualmente conocido como virus de la inmunodeficiencia humana (VIH), fue identificado en 1983. En 2023 se cumplieron 40 años del diagnóstico del primer caso de sida asistido en el Hospital de Enfermedades Infecciosas "Francisco J. Muñiz" de la Ciudad Autónoma de Buenos Aires. Se presenta a dicho paciente y se realiza un comentario sobre los inicios de la pandemia en el país

Between July 1979 and April 1981, the first cases of Pneumocystis carinii pneumonia in previously healthy young homosexual men, with significant alterations in cellular immunity, were reported in New York and Los Angeles (USA). New cases of patients with two or more opportunistic infections and Kaposi's sarcoma were simultaneously reported. AIDS was a new disease whose causal agent, currently known as the human immunodeficiency virus (HIV), was identified in 1983. In 2023, 40 years have passed since the diagnosis of the first case of AIDS assisted at the "Francisco" Hospital for Infectious Diseases. J. Muñiz" of the Autonomous City of Buenos Aires. Said patient is introduced and a comment is made about the beginnings of the pandemic in the country

Causa inusual de meningitis en pacientes infectados por HIV-1 / Unusual cause of meningitis in HIV-1 infectedpatient6. Corredoira J, Garcia-Garrote F, Rabuñal R, et al. Association between bacteremia due to Streptococcus gallolyticus subsp. gallolyticus (S. bovis I) and colorectal neoplasia: a case-control study. Clin Infect Dis 2012; 55:491-967. Sheng WH, Chuang YC, Teng LJ, Hsueh PR. Bacteremia due to Streptococcus gallolyticus subspecies pasteuri

La infección por HIV suele ser un campo propicio para la aparición de complicaciones de causas inusuales, entre ellas, las infecciones por gérmenes extremadamente infrecuentes. Las distintas subespecies de Streptococcus bovis suelen presentarse como bacteriemias o endocar-ditis asociadas, con mucha frecuencia, a tumores benignos o malignos de las regiones colorrectal, gástrica, pancreática o hepatobiliar.Se presenta un caso raro de meningitis por Streptoccocus gallolyticusen un paciente adulto infectado por HIV, sin evidencia alguna de las asociaciones o localizaciones mencionadas y con características clíni-cas y licuorales que pueden inducir a pensar en diagnósticos distintos y, por ende, a tratamientos no apropiados.Un sistema inmunológico deteriorado suele ser el escenario determi-nante para la emergencia de estas raras complicaciones

HIV infectionis, usually, a favorable field for the development of complications from unusual causes including infections with extremely raregerms. The different subspecies of Streptococcus bovis often present as bacteriemias or endocarditis, most frequently associated with benign or malignant tumors of the colorectal, gastric, pancreatic or hepatobiliary regions.A rare case of meningitis due to Streptoccocus gallolyticus in an adult patient infected by HIV is presented without any evidence of associations or mentioned locations and with clinical and the cerebrospinal fluid features that induce to other diagnoses and subsequent inappropriate treatment.A deteriorated immune system is the determining factor for the emergence of these rare complications

Cholesterol Levels in HIV- and/or HCV-Infected Drug Users Living in Argentina.

Improved understanding of cholesterol levels in HIV- and hepatitis C virus (HCV)-infected persons in Argentina will guide optimal antiretroviral therapy. The authors conducted a cross-sectional study in Argentina to describe associations between HIV, HCV, and cholesterol. Of the 202 participants, 21 were HIV infected, 15 were HCV infected, 46 were HIV/HCV coinfected, and 120 were HIV/HCV uninfected. HIV/HCV-uninfected participants had the highest total cholesterol (TC) and low-density lipoprotein (LDL) levels. Multivariate modeling revealed that HIV/HCV-coinfected patients had the lowest TC levels (-28.7 mg/dL, P < .001) compared to the HIV/HCV-uninfected reference group. Hepatitis C virus and HIV/HCV coinfection were associated with lower LDL levels (-21.4 mg/dL, P = .001 and -20.3 mg/dL, P < .0001, respectively). HIV and HIV/HCV coinfection, but not HCV alone, were associated with lower high-density lipoprotein levels (-9.1 mg/dL, P = .0008 and -6.8 mg/dL, P = .0006, respectively). Further study is needed to examine whether the more favorable lipid profile observed in HIV/HCV-coinfected persons is associated with a reduction in cardiovascular risk.

Enfermedad de Castleman e infección por HIV. Presentación de dos casos y revisión de la literatura / Castleman disease and HIV infection. Presentation of two cases and revision of the literature

La enfermedad de Castleman es un desorden linfoprolifera-tivo de origen aún incierto pero, en principio, relacionado con una dis-función de las células dendríticas foliculares y con una producción al-terada de distintas citoquinas, la mayor parte de ellas con actividad proinflamatoria y responsable de la sintomatología que presentan los pacientes.La relación con la presencia del HHV8, especialmente de las formas graves, ha sido ampliamente documentada en los últimos años y su desarrollo en el marco de la infección por el HIV permite una evolu-ción desafortunada de esta asociación morbosa presentando una ten-dencia importante hacia el desarrollo de patologías neoplásicas tales como la enfermedad de Kaposi y distintos tipos de linfomas.Se presentan dos casos de enfermedad de Castleman asociados a in-fección por HIV y HHV8 y se describe el contexto patogénico donde se desarrollan

Castleman ́s disease is a lymphoproliferative disorder of uncertain origin but, principally, related to dysfunction of follicular dendritic cells and impaired production of various cytokines, most of which have proinflammatory activity and are responsible for the symptoms that patients present.The relationship between Castleman ́s disease and HHV8, especially in severe forms, has been well documented in the last years. This morbid association is related to an unfortunate evolution in the context of HIV infection, presenting an increased risk of neoplastic disorders such as Kaposi ́s disease and various types of lymphomas.Two cases of Castleman ́s disease associated with HHV8 and HIV infection, and the pathogenic context in which they developed, are presented and described

In vitro replication competence of a hepatitis B genotype D/A recombinant virus: dissimilar biological behaviour regarding its parental genotypes.

Hepatitis B virus (HBV) DNA recombinants contribute to ~30% of the overall full-length sequences already deposited in GenBank. However, their biological behaviour has not been analysed so far. In this study, the in vitro replication kinetics of the first D/A recombinant from the American continent differed from its parental genotypes, exhibiting higher extracellular levels of HBV DNA and hepatitis B e antigen. Southern blots of intracellular core-associated HBV DNA were in agreement with such results. Because this recombinant was obtained from an Argentinian injecting drug user belonging to a vulnerable community, these results are of singular relevance for regional public health. Further in vivo studies are urgently needed to determine the pathogenicity of these replicative competent clones.

A nucleoside- and ritonavir-sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment-naïve HIV-infected patients: SPARTAN study results.

BACKGROUND: Nucleoside and ritonavir (RTV) toxicities have led to increased interest in nucleoside reverse transcriptase inhibitors (NRTIs) and RTV-sparing antiretroviral regimens. SPARTAN was a multicenter, randomized, open-label, noncomparative pilot study evaluating the efficacy, safety, and resistance profile of an investigational NRTI- and RTV-sparing regimen (experimental atazanavir [ATV] dose 300 mg bid + raltegravir [RAL] 400 mg bid [ATV+RAL]). The reference regimen consisted of ATV 300 mg/RTV 100 mg qd + tenofovir (TDF) 300 mg/emtricitabine (FTC) 200 mg qd (ATV/r+TDF/FTC). METHODS: Treatment-naïve HIV-infected patients with HIV-RNA ≥5,000 copies/mL were randomized 2:1 to receive twice-daily ATV+RAL (n=63) or once-daily ATV/r+TDF/FTC (n=31). Efficacy at 24 weeks was determined by confirmed virologic response (CVR; HIV-RNA <50 copies/mL) with noncom-pleters counted as failures based on all treated subjects. RESULTS: The proportion of patients with CVR HIV RNA <50 copies/mL at week 24 was 74.6% (47/63) in the ATV+RAL arm and 63.3% (19/30) in the ATV/r+TDF/FTC arm. Systemic exposure to ATV in the ATV+RAL regimen was higher than historically observed with ATV/r+TDF/ FTC. Incidence of Grade 4 hyperbilirubinemia was higher on ATV+RAL (20.6%; 13/63) than on ATV/r+TDF/FTC (0%). The criteria for resistance testing (virologic failure [VF]: HIV-RNA ≥400 copies/mL) was met in 6/63 patients on ATV+RAL, and 1/30 on ATV/r+TDF/FTC; 4 VFs on ATV+RAL developed RAL resistance. CONCLUSIONS: ATV+RAL, an experimental NRTI- and RTV-sparing regimen, achieved virologic suppression rates comparable to current standards of care for treatment-naïve patients. The overall profile did not appear optimal for further clinical development given its development of resistance to RAL and higher rates of hyperbilirubinemia with twice-daily ATV compared with ATV/RTV.

Importancia de la difilobotriosis humana para el turismo / Significance of human diphyllobothriasis for tourism

La difilobotriosis es una infección parasitaria causada por cestodos del género Diphyllobothrium, cuyos adultos se desarrollan tanto en mamíferos como en aves. El hombre es también hospedero definitivo y los estadios juveniles se establecen en copépodos y peces teleósteos. En las zonas lacustres del sur argentino existen condiciones ecológicas propicias para la instalación de esta endemia. Durante el período 2002-2006 se atendieron en el Hospital de Enfermedades Infecciosas Francisco J. Muñiz de la Ciudad de Buenos Aires (Argentina) 6 casos con difilobotriosis humana, a los cuales se les realizo el diagnóstico epidemiológico, clínico y de laboratorio. Se efectuó el tratamiento antiparasitario específico y el seguimiento correspondiente postratamiento. Todos los casos evolucionaron favorablemente. La importancia de esta publicación reside en alertar a los agentes que trabajan en salud sobre la presencia de esta patología emergente en zonas patagónicas andinas y en pacientes que consumen pescado crudo o poco cocido, provenientes de esa zona. Se destaca la posibilidad de adquirir esta infección íctica por el consumo de ciertos platos de origen oriental, como el sushi y el sashimi, en otras zonas no endémicas.

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.

High rates of serum selenium deficiency among HIV- and HCV-infected and uninfected drug users in Buenos Aires, Argentina.

OBJECTIVE: To describe the prevalence of low serum Se and determine whether HIV, hepatitis C virus (HCV) and/or the types of drugs used are associated with serum Se in a cohort of infected and uninfected drug users. DESIGN: Independent correlates of low serum Se levels based on data collected from food recalls, physical examinations and clinical questionnaires were identified using multivariate regression analysis. SETTING: Buenos Aires, Argentina SUBJECTS: A total of 205 (twenty-five female and 180 male) former and current drug users. RESULTS: Drug users had an average serum Se level of 69·8 (sd 32·8) µg/d, [corrected] and 82 % were considered deficient (<85 µg/l). [corrected] Multivariate analyses found that HIV- and/or HCV-infected individuals had lower mean Se compared with healthy, uninfected drug users (HIV/HCV co-infection: -25·3 µg/l (se 7·6), P = 0·001; HIV alone: -28·9 µg/l (se 6·9), P < 0·001; HCV alone: -19·4 µg/l (se 7·1), P = 0·006). Current and previous drug use was associated with higher serum Se. Cigarette smoking and heavy alcohol consumption were not found to be associated with Se status. CONCLUSIONS: Low serum Se levels are highly prevalent among drug users in Buenos Aires, Argentina. Se supplementation and/or dietary interventions may be warranted in drug users who are at high risk for HIV and/or HCV infection.

Role of -675 4G/5G in the plasminogen activator inhibitor-1 gene and -308G/A tumor necrosis factor-α gene polymorphisms in obese Argentinean patients.

AIM: Plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor-α (TNF-α) are increased in the circulation of obese persons. Because a direct link between PAI-1 and TNF-α in obesity has been observed, they are candidate genes for the development of obesity. We sought to evaluate the relation between the genotypic and allelic frequencies of the -675 4G/5G PAI-1 and -308 G/A TNF-α polymorphisms and their association with the risk for obesity in an Argentinean population. METHODS: A group of 110 consecutive obese persons and a group of 111 lean controls were recruited. Polymerase chain reaction was used to determine the frequency of PAI-1 and TNF-α polymorphisms; serum fasting glucose, insulin, and lipid levels were measured by standard methods. Insulin sensitivity was evaluated by using homeostasis model assessment. RESULTS: The -308 TNF-α and -675 4G/5G PAI-1 genotype distribution did not significantly differ between the groups (p=0.544 and p=0.327, respectively). Homeostasis model assessment was the only positive independent determinant of body mass index (R(2)=0.493; p<0.001). CONCLUSION: The -675 4G/5G PAI-1 and the -308 TNF-α polymorphism variants tested in this study, individually or combined, were not associated with obesity in an Argentinean population.

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

BACKGROUND: 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. OBJECTIVES: The aim of this work was to investigate the presence of HIV dual infections in HIV-infected individuals with high probability of reinfection STUDY DESIGN: Blood samples were collected from 23 HIV positive patients with the risk of reinfection from Buenos Aires. A fragment of the HIV gene pol was amplified and phylogenetic analyses were performed. Antiretroviral drug resistance patterns of all the sequences were analyzed. RESULTS: 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. CONCLUSIONS: 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.

Variables that influence HIV-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis.

BACKGROUND: The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF HIV-1 viral load and HIV-1 plasma viral load; and (3) CSF leukocyte count and the peripheral blood CD4+ T lymphocyte count. METHODS: Our approach was to use a prospective collection and analysis of pre-treatment, paired CSF and plasma samples from antiretroviral-naive HIV-positive patients with cryptococcal meningitis and assisted at the Francisco J Muñiz Hospital, Buenos Aires, Argentina (period: 2004 to 2006). We measured HIV CSF and plasma levels by polymerase chain reaction using the Cobas Amplicor HIV-1 Monitor Test version 1.5 (Roche). Data were processed with Statistix 7.0 software (linear regression analysis). RESULTS: Samples from 34 patients were analyzed. CSF leukocyte count showed statistically significant correlation with CSF HIV-1 viral load (r = 0.4, 95% CI = 0.13-0.63, p = 0.01). No correlation was found with the plasma viral load, CSF protein concentration and cryptococcal antigen titer. A positive correlation was found between peripheral blood CD4+ T lymphocyte count and the CSF leukocyte count (r = 0.44, 95% CI = 0.125-0.674, p = 0.0123). CONCLUSION: Our study suggests that CSF leukocyte count influences CSF HIV-1 viral load in patients with meningitis caused by Cryptococcus neoformans.

Thrombophilia in human immunodeficiency virus-infected patients with osteonecrosis: Is there a real connection? The first case-control study.

Several reports have described an increased incidence of osteonecrosis in human immunodeficiency virus-infected patients (HIV+), but the cause has not been established. The association between thrombophilia and osteonecrosis in HIV+ was studied. A case-control study in HIV+, 19 cases and 38 controls, was designed. Magnetic resonance imaging was made in both groups to confirm or exclude hip osteonecrosis. The extensive tests of thrombophilia were measured, and the clinical data were recorded, nadir of CD4(+) cell count and well-known risk factors for osteonecrosis. Thrombophilia has been frequently found both in patients with and without osteonecrosis (thrombophilia, 68.4% vs 60.5%), but no specific thrombophilia tests were significantly associated with osteonecrosis. A low nadir of CD4(+) (<60 cells/microL) and corticoid use were significantly (P < .05) associated with osteonecrosis. In multivariate analysis, only nadir of CD4(+) <60 cells/microL remained a predictor of osteonecrosis (odds ratio = 7.33; 95% confidence interval, 1.80-29.82, P = .005). Thrombophilia might have a limited role in the development of osteonecrosis in HIV+. Nadir of CD4(+) <60 cells/microL and corticoid use were main factors.

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.