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.

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.

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.

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.

Circulating Epstein-Barr virus (EBV) in HIV-infected patients and its relation with primary brain lymphoma.

OBJECTIVE: To analyze Epstein-Barr virus (EBV) load at different HIV infection stages and its relation with brain lymphoma. DESIGN: A cross-sectional study was conducted on 172 HIV-infected individuals: 62 asymptomatic HIV carriers (group A), 30 HIV progressors (group B), 73 AIDS patients (group C), seven AIDS patients with brain lymphoma (group C-BL); and 26 blood donors (group BD) as healthy carriers. EBV load was measured in peripheral blood mononuclear cells (PBMC) and plasma samples using a semi-quantitative PCR method. RESULTS: PBMC-EBV levels in HIV-infected patients were higher than in the blood donors (p<0.05). No differences in PBMC-EBV loads were found in groups A, B, or C (p>0.05), while the C-BL group had significantly lower levels (p<0.05). Similar PBMC-EBV loads were seen in HIV-infected patients with CD4+ T cell counts higher than 50/mm(3) (p>0.05), while significantly lower levels were found in cases with less than 50 cells/mm(3) (p<0.05). In all HIV-infected patients, plasma-EBV load was lower than, or similar to, PBMC-EBV load, unlike 2/7 HIV-positive brain lymphoma patients. CONCLUSIONS: During HIV infection PBMC-EBV load rises in comparison to healthy carriers, but decreases when immunosuppression progresses and CD4+ T cell count becomes <50/mm(3). Circulating EBV is mainly cell-associated in the HIV-infected population. Neither PBMC-EBV nor plasma-EBV loads would be useful to diagnose brain lymphoma in AIDS patients.

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.

A randomized trial to evaluate lopinavir/ritonavir versus saquinavir/ritonavir in HIV-1-infected patients: the MaxCmin2 trial.

OBJECTIVE: To assess the rate of protocol-defined treatment failure and safety of lopinavir/ritonavir (LPV/r) and saquinavir/ritonavir (SAQ/r). DESIGN: Open-label, prospective, randomized (1:1), international multi-centre trial. METHODS: Adult HIV-1-infected patients were assigned LPV/r 400/100 mg twice daily or SAQ/r 1000/100 mg twice daily with two or more nucleoside reverse transcriptase inhibitors (NRTIs)/non-NRTIs. All patients, whether on or off the assigned treatment, were followed for 48 weeks. RESULTS: Of 339 randomized patients, 324 initiated assigned treatment (intention-to-treat/exposed [ITT/e] population). At 48 weeks, treatment failure occurred in 29/163 (18%) and 53/161 (33%) of patients in the LPV/r and SAQ/r arms, respectively (ITT/e, P = 0.002, log rank test). In an analysis that also considered those patients who discontinued treatment as having failed treatment (ITT/e/discontinuation = failure), 40/161 (25%) LPV/r-treated individuals versus 63/161 (39%) SAQ/R-treated individuals failed treatment (P = 0.005, log rank test). Discontinuation of the assigned treatment occurred in 23/163 (14%) patients in the LPV/r-treated group, compared with 48/161 (300%) in the SAQ/r-treated group (ITT/e; P = 0.001). The primary reasons for premature discontinuation were non-fatal adverse events (LPV/r: 12/163; SAQ/r: 21/161) and patients' choice (LPV/r: 7/163; SAQ/r: 8/161). In the on-treatment analysis of time to treatment failure, no difference was observed between the two arms (P = 0.27, log rank test). CONCLUSION: LPV/r had better antiretroviral effects compared with SAQ/r at the doses and in the formulations studied. This may have been a result of patients' preferences and ability to adhere to assigned therapy, rather than a result of differences in the intrinsic potency of the study protease inhibitors.

Pharmacokinetics of indinavir/ritonavir (800/100 mg twice a day) combined with efavirenz in HIV-infected patients.

A pharmacokinetics study was performed in HIV-infected patients who used indinavir/ritonavir (800/100 mg twice a day) plus efavirenz in the European and South American Study of Indinavir, Efavirenz and Ritonavir. Indinavir plasma concentrations were similar to values previously obtained in healthy volunteers who used the same combination. Efavirenz concentrations were higher than reported before. The pharmacokinetic data suggest that indinavir/ritonavir plus efavirenz (without dose modifications) should be effective in treatment-naive patients, and this was supported by the treatment response of the participants.

Bloodborne and sexually transmitted infections in drug users in a hospital in Buenos Aires, Argentina.

Injection drug users (IDUs) constitute a population highly vulnerable to infections transmitted by blood or sexual relations. Social problems and marginalization hinder IDUs from accessing the health care system. The rates of prevalence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus infections in IDUs are high, and they have become of great concern for the Argentinean health care system. An integral frame oriented to identifying the extent of the different individual risk factors, and to enhancing social circumstances, has shown a significant benefit in terms of personal and social matters. These risk factors were analyzed according to a severity of drug abuse scoring system. At the beginning of the study, only 7 of 108 patients were in a low gravity stage, whereas there were 40 patients in the low gravity stage by the end of the study (P<.0001). On the basis of our results, we conclude that low-cost nonmedical tools are effective and have a high impact on patients' health.

Endothelial markers and HIV infection in the era of highly active antiretroviral treatment.

Many circumstances can induce activation and/or injury of the endothelium that plays a role in the development of vascular complications. Raised plasma levels of endothelial markers such as von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble vascular cell adhesion molecule-1 (sVCAM-1) have a prognostic and/or diagnostic value. Human immunodeficiency virus-infected patients (HIV+) have a clustering of conditions that activate or injure the endothelium. Highly active antiretroviral treatment produces adverse effects such as dyslipemia, insulin resistance (IR) and body fat changes (named lipodystrophy syndrome) which may contribute to aggravate their endothelial perturbation. The aim of this study was to measure lipid profile, insulin resistance status, and endothelial markers in 38 HIV+ naive of antiretroviral treatment and 63 HIV+ under highly active antiretroviral treatment (33 with lipodystrophy syndrome and 30 without it). Body fat distribution was also evaluated by dual-energy X-ray absorptiometry (DEXA) analysis. Thirty-one HIV negative subjects were used as controls. We looked for association between variables. Insulin resistance status was a common finding in the four groups. Lipodystrophic patients presented an atherothrombotic lipid profile [elevated levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-chol) and apolipoprotein-B (APO-B)] and a strong loss of fat in legs and arms (lipoatrophy). All endothelial markers evaluated in our naive patients were higher as compared to control group. sVCAM-1 in HIV+ under therapy without lipodystrophy syndrome showed significantly decreased levels as compared to naive group (487 vs. 666 ng/ml) and vWF and sTM tended to diminish although they did not show a significant difference (130% vs. 170%, 41 vs. 45 ng/ml, respectively). Lipodystrophic patients showed a tendency to increased levels of endothelial activation markers (sVCAM-1: 500 ng/ml and vWF: 154%) together with significantly increased levels of an endothelial injury marker (sTM: 50 ng/ml) with respect to HIV+ under therapy without lipodystrophy syndrome. Plasma levels of sTM, as an endothelial injury marker, correlated with peripheral lipoatrophy (rho = -0.357) in lipodystrophic patients. In conclusion, despite the beneficial immunology effect of highly active antiretroviral treatment and the apparent decrease in the endothelial perturbation, the patients who develop lipodystrophy present altered endothelial markers and other risk factors, such as IR and dyslipemia, which turn them into a high atherothrombotic risk group.

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.

[Plasma homocysteine in human immunodeficiency virus infected patient]. / Homocisteína plasmatica en infectados con el virus de la inmunodeficiencia humana.

UNLABELLED: Weak hyperhomocysteinemia is a risk factor for the development of atherothrombotic vascular complication. Their plasma levels are affected by nutritional and pharmacologic factors, tobacco, certain metabolic state and gender. In HIV+ patients, the wasting syndrome or chronic diarrheas could affect the levels of homocysteine (Hcy), as well as some adverse effects of the new antiretroviral therapies (lipodystrophy syndrome: insulin resistance and/or dislypemia). The levels of Hcy were evaluated in 53 HIV+ patients without any treatment and in 75 HIV+ under treatment with and without metabolic disturbances (n = 43; n = 32, respectively). CONTROL GROUP: 32 HIV negative individuals. We looked for association with folic acid, vitamin B12, lipids, insulin resistance status, activation platelets (soluble P-selectin) and endothelial injury (soluble trombomodulin) markers; and also their relation with tobacco, disease status and kind of treatment. There were no statistically significant differences in the mean levels of vitamin B12, Hcy, P-selectin and insulin resistance status between the control group and the HIV+; 16.4% of the 128 HIV+ patients had Hcy > or = 15 mumol/L and the control group had 12.9% (p = 0.617). The levels of Hcy correlated with the levels of folic acid (Rho = -0.314, p < 0.01) and age (Rho = 0.277, p < 0.01) among HIV+. There were no statistically significant differences in the levels of Hcy neither between smokers and non smokers (p = 0.452) nor between HIV+ AIDS or HIV+ no AIDS (p = 0.774) nor with the use of certain antiretrovirals (p = 0.801). The hyperhomocysteinemia (a well known atherothrombotic risk factor) is not frequently associated with HIV infected patients. The levels of Hcy would not seem to be influenced either by the HIV condition or by the antiretroviral treatments or their adverse effects.

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

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.

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.