Contribution of APOA5, APOC3, CETP, ABCA1 and SIK3 genetic variants to hypertriglyceridemia development in Mexican HIV-patients receiving antiretroviral therapy.

OBJECTIVE: To investigate the impact of single nucleotide polymorphisms (SNPs) from APOA5, APOC3, CETP, ATP binding cassette transporter A1 and SIK3 genes in the development of hypertriglyceridemia in HIV patients under antiretroviral therapy. MATERIAL AND METHODS: A case-control study was developed. Leukocytic genomic DNA was extracted and genotyping for SNPs rs662799, rs964184, rs5128, rs2854116, rs2854117, rs3764261, rs4149310, rs4149267 and rs139961185 was performed by real time-PCR using TaqMan allelic discrimination assays, in Mexican mestizo patients with HIV infection, with hypertriglyceridemia (>1.7 mmol/L) under antiretroviral therapy. Genetic variants were also investigated in a control group of normolipidemic HIV patients (≤ 1.7 mmol/L). Haplotypes and gene interactions were analyzed. RESULTS: A total of 602 HIV patients were genotyped (316 cases and 286 controls). Age and antiretroviral regimen based on protease inhibitors were associated with hypertriglyceridemia (P = 0.0001 and P = 0.0002. respectively). SNP rs964184 GG genotype in APOA5 gene exhibited the highest association with hypertriglyceridemia risk (OR, 3.2, 95% CI, 1.7-5.8, P = 0.0001); followed by SNP rs139961185 in SIK3 gene (OR = 2.3; (95% CI, 1.1-4.8; P = 0.03 for AA vs. AG genotype; and APOC3 rs5128 GG genotype, (OR, 2.2; 95% CI, 1.1-4.9; P = 0.04) under codominant models. These associations were maintained in the adjusted analysis by age and protease inhibitors based antiretroviral regimens. CONCLUSIONS: This study reveals an association between rs964184 in APOA5; rs5128 in APOC3 and rs139961185 in SIK3 and high triglyceride concentrations in Mexican HIV-patients receiving protease inhibitors. These genetic factors may influence the adverse effects related to antiretroviral therapy.

A decrease in hepatitis C virus RNA to undetectable levels in chronic hepatitis C patients after PegIFNα + RVB or sofosbuvir + NS5A inhibitor treatment is associated with decreased insulin resistance and persistent oxidative stress.

Oxidative stress (OS) and insulin resistance (IR) induced by hepatitis C virus (HCV) infection, are involved in the development of chronic hepatitis C (CHC) complications and progression to hepatocellular carcinoma. The aim of this study was to investigate the effect of pegylated interferon alpha (IFNα) + ribavirin (PegIFNα+RVB) or sofosbuvir + NS5A inhibitor (SOF+InNS5A) on IR and the components of OS. HCV was genotyped in 20 CHC patients grouped by treatment with either PegIFNα+RVB (n = 10) or SOF+InNS5A (n = 10). The treatment's effect on OS-induced damage to lipids (HNE-HDL), proteins (advanced glycation end products [AGEs]), and DNA (8-OHdG) as well as the concentrations of proinflammatory cytokines (IL-2, TNFα, IFNγ), ALT, AST, GSH and platelets was determined. Superoxide dismutase (SOD) and catalase activity as well as IR, determined by the HOMA1-IR index, was evaluated. The HCV genotypes (GT) found were GT1b (45%), GT1a (30%), GT2b (20%), and GT2a (5%). Viral RNA became undetectable by week 12 with SOF+InNS5A in 100% of the cases and with PegIFNα+RVB in 70% of the cases. After viral RNA became undetectable, regardless of treatment and GT, a significant increase in the platelet concentration and SOD activity was observed, whereas ALT, insulin, and IR decreased (p < 0.05). However, only for the SOF+InNS5A treated group was there an increase in oxidative damage to lipids (p < 0.017) and proteins (p < 0.05). None of the other parameters demonstrated any differences. These data confirm that OS persisted after treatment with either SOF+InNS5A or PegIFNα+RVB. IR could be considered a response biomarker to treatment with direct-acting antivirals.

Comparison of direct sequencing of the NS5B region with the Versant HCV genotype 2.0 assay for genotyping of viral isolates in Mexico.

Hepatitis C virus (HCV) infection affects an estimated 71 million people worldwide. HCV is classified into eight genotypes and >70 subtypes. Determination of HCV genotype is important for selection of type and duration of antiviral therapy, and genotype is also a predictor of treatment response. The most commonly used HCV genotyping method in clinical laboratories is a hybridization-based line probe assay (LiPA; Versant HCV Genotype 2.0). However, these methods have a lack of specificity in genotype identification and subtype assignment. Here, we compared the performance of Versant HCV Genotype 2.0 with the gold standard direct sequencing of the NS5B region, in 97 samples from Mexican patients. We found a genotypic concordance of 63.9% between these methods. While 68 samples (70%) were classified into HCV genotype 1 (GT1) by NS5B sequencing, it was not true for 17 samples (17.5%), which were not match HCV subtype by LiPA. Furthermore, nine of the 33 samples classified by NS5B sequencing as GT1a were not identified by LiPA. Use of direct sequencing could improve selection of the optimal therapy, avoid possible failures of therapy and avoid high costs resulting from incorrect genotyping tests in settings without broad access to pangenotypic regimens.

Case report: Identification of recombinant HCV genotype 1b-2b by viral sequencing in two patients with treatment failure, who responded to re-treatment with sofosbuvir and daclatasvir.

Hepatitis C virus (HCV) infection is a global health problem. HCV has been classified into seven genotypes and >67 subtypes. Genotyping is necessary to enable selection of appropriate treatments. The commercial molecular techniques currently used do not identify some HCV subtypes, mixed infections and recombinant forms. In this study, the core-E1 and NS5B regions were sequenced and phylogenetically analysed to identify infections by HCV recombinant genotype 1b-2b in two patients who had initially been diagnosed with HCV genotype 2 infection by reverse hybridization with a Versant HCV Genotype 2.0 Assay. Response to treatment was monitored by viral kinetics. Therapeutic failure occurred with initial treatment with PEGylated interferon-α2b and ribavirin, but the use of sofosbuvir and daclatasvir on a re-treatment regimen after reclassification of the infecting virus resulted in a sustained virologic response. The use of a sequencing approach in treatment-naïve infected patients could enable physicians to select the optimal therapy and avoid possible relapses and adverse reactions associated with antiviral therapy.

Strong correlation between protein reagent strip and protein-to-creatinine ratio for detection of renal dysfunction in HIV-infected patients: a cross-sectional study.

BACKGROUND: Tubular dysfunction is common in HIV-infected people and detection of proteinuria is essential to identify this problem. In low-income countries, resources for detection of proteinuria using the Kidney Disease Improve Global Outcomes (KDIGO) gold standard urinary protein/creatinine ratio (uPCR) is rarely possible, and use of the protein reagent strip (PRS) could be an option in these places. The aims of this study were to establish the concordance between PRS and uPCR to detect tubular proteinuria in HIV-infected people, and to assess the sensitivity and specificity of PRS as a diagnostic method in this group. METHODS: A cross-sectional study was conducted to evaluate the correlation between the two techniques to detect protein in urine. Participants were enrolled for a period of 6 months. The measurements were performed in participants who were on highly active antiretroviral therapy (HAART) or prior to the start of treatment. Proteinuria was defined as uPCR ≥ 150 mg/g, and/or ≥ trace on PRS. A phi coefficient was calculated to establish the degree of correlation. We assessed the sensitivity and specificity of PRS compared with uPCR using standard methods. RESULTS: A total of 799 subjects were included. Of these, 737 (92%) were men. The mean age was 32.9 years (±10.1 years). Most (561, 70%) were on antiretroviral treatment. The mean estimated glomerular filtration rate (eGFR) calculated according to Modification of Diet in Renal Disease (MDRD)-4 was 113.0 mL/min (±22.6). Comorbidities included diabetes mellitus (10, 1.3%) and hypertension (17, 2.1%). The prevalence of proteinuria detected by PRS was 8.3% (n = 66) and by uPCR 10.6% (n = 85). The concordance assessed by phi correlation coefficient was 0.70, p < 0.001, with a sensitivity of 51.7% (95% confidence interval [CI] 41%-62%) and specificity 97% (95% CI 39%-97%). CONCLUSIONS: There is a high concordance between detection of proteinuria by PRS and uPCR. Therefore, in low-income countries PRS can be helpful for detecting tubular damage in people infected with HIV.

Effectiveness and risk factors for virological outcome of darunavir-based therapy for treatment-experienced HIV-infected patients.

OBJECTIVE: We evaluated the effectiveness of darunavir (DRV) treatment plus an optimized background regimen in 120 HIV-1 treatment-experienced patients. DESIGN: Retrospective cohort, multicenter study. METHODS: Adults >16 years with virological treatment failure starting therapy with a DRV-containing regimen were included. Effectiveness was evaluated as the percentage of patients with an undetectable HIV-1 RNA viral load (<50 and <200 copies/mL) after 48 weeks, and changes in CD4+ cell counts. We evaluated the risk factors associated with treatment failure. RESULTS: Of the cohort, 83 % were men with a median age of 45 years (interquartile range, IQR 40-51). They had experienced treatment for a median of 13 years (IQR 9-17) with a median of six previous regimens (IQR 4-7), all using protease inhibitors. After treatment, 82 % (95 % confidence interval, CI 74-88 %) of patients had an HIV-1 RNA viral load <200 copies/mL and 69 % (95 % CI 60-76 %) had <50 copies/mL. The CD4+ cell count increased by 378 cells/µL (IQR 252-559; P < 0.001 vs. baseline). Risk factors associated with poor outcome were age >40 years [odds ratio, OR 0.15 (95 % CI 0.10-0.78); P = 0.015], use of raltegravir in the regimen [OR 0.37 (95 % CI 0.10-0.97); P = 0.046], and baseline CD4+ cell count <200 cells/µL [OR 2.79 (95 % CI 1.11-6.97); P = 0.028]. CONCLUSION: In this Mexican cohort Darunavir was metabolically safe, well tolerated and achieved high rates of virological suppression in highly treatment-experienced patients infected with HIV-1.

Effectiveness of enfuvirtide in a cohort of highly antiretroviral-experienced HIV-1-infected patients in Mexico.

BACKGROUND: Treatments in patients with multidrug resistance often involve the use of multiple agents with partial antiviral activity and overlapping metabolic toxicities. Enfuvirtide is therefore a welcome addition to the antiretroviral management of patients with multiclass resistant virus, given the low risk of systemic toxicities and novel mechanism of action relative to existing drug classes. The aim of this study was to evaluate the effectiveness of ENF plus optimized background regimen (OBR) in a Mexican cohort of highly HIV-1 ARV-experienced patients. METHODS: Prospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ENF-containing regimen. The effectiveness of ENF treatment was evaluated with percentages of undetectable HIV-1 RNA viral load after 24 and 48 weeks of treatment, and changes in CD4+ cell counts. RESULTS: Forty patients >18 years were included. After 24 weeks of treatment, 91% of patients had HIV-1 RNA viral load <400 copies/mL and 65.8% had <50 copies/mL. At week 48 of treatment, 81.4% of the patients had HIV-1 RNA <400 copies/mL and 55.5% had <50 copies/mL; in both cases p <0.0001 compared to baseline. Increase CD4+ cells were also statistically significant at weeks 24 and 48 with respect to the baseline. Pain at the site of injection was the main adverse event in 100% of patients. CONCLUSION: Our study provides clinically important evidence of the effectiveness and safety of ENF in highly ARV-experienced HIV-1-infected patients. These findings strengthen the results of previous randomized controlled trials with this agent.

Weight gain and metabolic disturbances in people living with HIV who start antiretroviral therapy with, or switch to, bictegravir/emtricitabine/tenofovir alafenamide after 48 weeks of treatment: A real-world prospective study.

BACKGROUND: People living with HIV (PLWH) starting or switching to an integrase strand transfer inhibitor-based regimen are more likely to experience weight gain than other classes of antiretroviral regimens. The aim of this study was to evaluate the weight gain and metabolic disturbances in PLWH who start antiretroviral therapy (ART) with bictegravir/emtricitabine/tenofovir alafenamide and in individuals who switch from another ART to BIC/FTC/TAF after 48 weeks. METHODS: A prospective longitudinal study was conducted in an HIV clinic in Mexico. Weight and metabolic parameters were measured at baseline, 24 and 48 weeks. A paired t test and Wilcoxon signed-rank test were applied to evaluate weight and metabolic changes. RESULTS: 160 participants completed measurements, median age was 29 (IQR 26-32) and 30 (IQR 27-34) years old for the treatment-naïve and switch group respectively. In the treatment-naïve group, mean weight change was 3.8 kg (±5.8) (p < .001) and BMI increased 1.3 kg/m2 (±2) (p < .001) at 48 weeks. Incidence of BMI >25 kg/m2 was 28% (95%CI; 18%-40%) and BMI >30 kg/m2 was 7% (95%CI; 2%-16%) at 48 weeks in treatment-naïve individuals. In the switch group, mean weight gain and BMI change at 48 weeks was 2.8 kg (±5.9) and 0.9 kg/m2 (±2.0) respectively (p < .001). Incidence of BMI >25 kg/m2 was 17% (95%CI; 8%-32%) and BMI >30 kg/m2 12.8% (95%CI; 5%-26%) at 48 weeks respectively. CONCLUSIONS: Weight gain should be considered when men PLWH are treated with BIC/FTC/TAF regimen. They should be informed about this possible adverse event and strategies of intervention.

Effect of antiretroviral therapy on inflammatory markers of endothelial dysfunction in HIV treatment-naïve infected patients.

The aim of this study was to evaluate the effect of antiretroviral therapy on inflammatory markers of endothelial dysfunction in HIV treatment-naïve infected patients. This was a prospective cohort study in HIV treatment-naïve infected patients. The patients were assigned to a untreated group or a treatment group according to the therapeutic strategy received. Patients in the treatment group received efavirenz or lopinavir/ritonavir, each given with zidovudine and lamivudine. HIV RNA, CD4(+) cell count, and the levels of hsCRP, sCD40L, sICAM-1, sVCAM-1, and sE-selectin were measured before and 12 weeks after treatment. Fifty patients were enrolled: 13 in the untreated group and 37 in the treatment group; 48 (96%) completed the follow-up. The mean (± SD) age was 33 ± 9 years, and 38 (79%) were men. The median pretreatment CD4(+) cell counts were 263 cells/ml (IQR 118-341) in the treatment group and 658 cells/ml (IQR 475-887) in the untreated group. In the treatment group, the median serum sVCAM-1 and sICAM-1 levels decreased by a small but significant amount (1,400 and 228 ng/ml, respectively, P<0.05) from before to after the 12 weeks. These levels did not change in the untreated group. Antiretroviral therapy is associated with a decrease in sVCAM-1 and sICAM-1 levels after 12 weeks of treatment.

Risk factors for mortality and clinical presentation of monkeypox.

OBJECTIVES: To describe risk factors for mortality and clinical characteristics in patients with mpox infection at a reference hospital in Mexico. DESIGN: A prospective cohort study was conducted from September to December 2022 at Hospital de Infectología La Raza National Medical Center. METHODS: Study participants were patients that met operational definition of confirmed case of mpox according to WHO criteria. Information was obtained through a case report form that included epidemiological, clinical, and biochemical information. The follow-up period was from initial evaluation for hospitalization until discharge due to clinical improvement or death. Written informed consent was obtained from all participants. RESULTS: Seventy-two patients were included in the analysis, 64 of 72 (88.9%) were people with HIV (PWH). Of the total of patients 71 of 72 (98.6%) were male, with a median age of 32 years old [95% confidence interval (CI), interquartile range (IQR) 27-37]. Coinfection with sexually transmitted infections was reported in 30 of 72 (41.7%). The overall mortality was five of 72 (6.9%). The incidence of mortality rate in PWH was 6.3%. Median days from onset of symptoms to death from any cause during hospitalization was 50 days (95% CI, IQR 38-62). Risk factors for mpox mortality in the bivariate analysis were CD4 + cells count ≤100 cells/µl at the time of assessment RR 20 (95% CI, IQR 6.6-60.2) ( P  < 0.001), absence of antiretroviral therapy RR 6.6 (95% CI, IQR 3.6-12.1) ( P  = 0.001) and ≥50 skin lesions at presentation RR 6.4 (95% CI, IQR 2.6-15.7) ( P  = 0.011). CONCLUSIONS: The clinical presentation between PWH and non-HIV patients was similar in this study, however, reported mortality was associated with advanced-HIV disease.

Comparative Analysis of Antimicrobial Antibodies between Mild and Severe COVID-19.

Patients with 2019 coronavirus disease (COVID-19) exhibit a broad spectrum of clinical presentations. A person's antimicrobial antibody profile, as partially shaped by past infection or vaccination, can reflect the immune system health that is critical to control and resolve the infection. We performed an explorative immunoproteomics study using microbial protein arrays displaying 318 full-length antigens from 77 viruses and 3 bacteria. We compared antimicrobial antibody profiles between 135 patients with mild COVID-19 disease and 215 patients with severe disease in 3 independent cohorts from Mexico and Italy. Severe disease patients were older with higher prevalence of comorbidities. We confirmed that severe disease patients elicited a stronger anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) response. We showed that antibodies against HCoV-229E and HcoV-NL63 but not against HcoV-HKU1 and HcoV-OC43 were also higher in those who had severe disease. We revealed that for a set of IgG and IgA antibodies targeting coronaviruses, herpesviruses, and other respiratory viruses, a subgroup of patients with the highest reactivity levels had a greater incidence of severe disease compared to those with mild disease across all three cohorts. On the contrary, fewer antibodies showed consistent greater prevalence in mild disease in all 3 cohorts. IMPORTANCE The clinical presentations of COVID-19 range from asymptomatic to critical illness that may lead to intensive care or even death. The health of the immune system, as partially shaped by past infections or vaccinations, is critical to control and resolve the infection. Using an innovative protein array platform, we surveyed antibodies against hundreds of full-length microbial antigens from 80 different viruses and bacteria in COVID-19 patients from different geographic regions with mild or severe disease. We not only confirmed the association of severe COVID-19 disease with higher reactivity of antibody responses to SARS-CoV-2 but also uncovered known and novel associations with antibody responses against herpesviruses and other respiratory viruses. Our study represents a significant step forward in understanding the factors contributing to COVID-19 disease severity. We also demonstrate the power of comprehensive antimicrobial antibody profiling in deciphering risk factors for severe COVID-19. We anticipate that our approach will have broad applications in infectious diseases.

Prevalence and resistance pattern of genotype G and H in chronic hepatitis B and HIV co-infected patients in Mexico.

OBJECTIVE: We estimated the prevalence and identified the resistance pattern of HBV genotypes H and G in HBV monoinfected and HIV co-infected patients. MATERIAL AND METHODS: A cross-sectional prevalence and analytic study were performed in chronic hepatitis B patients at the Hospital de Infectología, La Raza National Medical Center in Mexico City. Chronic HBV monoinfected and HIV co-infected patients were included. HBeAg, HBV viral load and genetic analysis of mutations were collected; CD4+ cells count from HIV co-infected patients and HIV RNA were measured. We calculated the prevalence and exact 95% binomial confidence interval and the Odds ratios (OR) with 95% confidence intervals to assess the relationship between the presence of risk factors and HBV genotypes H or G. RESULTS: We enrolled 77 patients, 67 men and 10 women with 37 HIV co-infected patients. The distribution of HBV genotypes was: HBV genotype H 55 (71% [95% CI 60% to 80%]), HBV genotype G 16 (20.7%), HBV genotype F 4 (5.1%) and HBV genotype A 2 (2.6%). The most frequent mutations presented in 8 HIV co-infected patients and one mono-infected patient with antiretroviral therapy (ART) experience were rtM204V and six of them showed genotype G (6/9). Mono-infected HBV patients exposed more probability to HBV genotype H than co-infected HIV patients OR 13.0 (CI 95% 3.40-49.79), p = 0.0001. In contrast co-infected patients presented less possibility to have genotype H, 0.56 (CI 95% 0.42-0.75). CONCLUSIONS: This study confirms the high prevalence of HBV genotype H in Mexico; furthermore, our results suggest that HBV genotype G predominates in co-infected patients. As well, rtM204V and rtL180M mutations are common in HBV-HIV co-infected patients with genotype G and ART experience.

Risk factors for HCV transmission in HIV-positive men who have sex with men in México.

PURPOSE: In the last two decades transmission of hepatitis C virus (HCV) in HIV positive men who have sex with men (MSM) has been reported globally. Chemsex and specific sexual practices have been identified as risk factors. Our study aimed to identify risk factors for HCV transmission in MSM living with HIV attending in Mexico. METHODS: We conducted a case-control study from April to December 2019 at the Hospital de Infectología "La Raza" National Medical Center, in Mexico City. A case was defined as an HIV-infected MSM with positive HCV-antibody test. For each case, 3 controls were included, defined as HIV infected MSM with negative HCV-antibody test. A self-questionnaire covering sexual practices and other risk factors for HCV transmission was applied. Bivariate analysis was performed to obtain odds ratio (OR) using Chi-square test. Independent risk factors were identified in a subsequent analysis performing a logistic regression model. RESULTS: A total of 324 patients participated in the study, 81 cases and 243 controls. Median age was 30.5 years (IQR: 18-52) and 28.8 years (IQR: 21-45) in the case and control group, respectively. Most prevalent HCV genotype was 1a (79%). In the logistic regression model, sharing straw during cocaine inhalation (OR: 9.03; 95% CI; 1.35-13.52; P = 0.003), sharing sex toys (OR: 17.53, 95% CI; 6.85-44.86; P = 0.002), and ethyl chloride use for chemsex (OR: 2.26; 95% CI; 1.29-5.56; P = 0.037) were significant risk factors for HCV infection. CONCLUSION: This study identifies risk factors for HCV transmission in Mexico in HIV positive MSM in congruence with the findings of many studies performed worldwide. This is the first study that indicates a possible association between ethyl chloride use in chemsex and HCV infection. Assessment of local populations for risk factors for HCV transmission may help to develop specifically targeted behavioral interventions to reduce HCV transmission.

[Prevalence of bacterial infections and patterns of bacterial susceptibility among patients with fever, neutropenia, and hematological neoplasias]. / Patrones de susceptibilidad bacteriana en infecciones en pacientes adultos con neoplasias hematológicas, fiebre y neutropenia.

Chemotherapy induces immunosuppression which is associated with a significant increase in the frequency and severity of infections. Neutropenia is the most important factor in determining susceptibility to bacterial infections. Our aim was to establish the prevalence of bacterial infections and bacterial susceptibility patterns in patients with fever, neutropenia and hematological neoplasias. Cultures were obtained prior empirical antimicrobial treatment. Susceptibility tests to antibiotics were performed for all microorganisms considered pathogens. Descriptive statistics were used for each variable. Differences between proportions were estimated by means of χ2 or Fisher's exact test. We included 85 patients.Primary bacteremia was the most frequent cause of fever (52%). Microorganisms most frequently isolated were:S. epidermidis (54.2%), E. coli (12.5%), S. aureus (8.3%). In susceptibility tests 88.5% of S. epidermidis strains were resistant to oxaciline (MIC > 8 µ/ml); E. coli was resistant to ceftazidime (50%) and trimethroprim/sulfamethoxazole (83%).In conclusion, gram-positive microorganisms are predominant in patients with fever and neutropenia followed by gram-negatives like E. coli. Predominance of gram-positives microorganism forces us to reconsider our current prophylactic and therapeutic antimicrobials regimens used in these patients.

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico.

BACKGROUND: The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. METHODOLOGY/PRINCIPAL FINDINGS: We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78-30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4-76.2) / 96.2% (95% CI, 93.2-98.0) for IAHE, 91.3% (95% CI, 84.2-96.0) / 90.9% (95% CI, 87.0-94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0-95.3) / 92.3% (95% CI, 88.6-95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3-72.5)/ 89.5% (95%CI, 86.0-93.0), 65.9% (95%CI, 56.0-75.8)/ 89.0% (95%CI, 85.2-92.9), 62.1% (95%CI, 44.4-79.7)/ 82.6% (95%CI, 71.7-93.6) and 34.9% (95%CI, 24.8-46.2)/ 67.3% (95%CI, 60.6-73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9-74.7)/ 58.8% (95%CI, 53.2-64.5), 70.8% (95%CI, 61.3-80.2)/ 52.9% (95%CI, 46.8-59.1), 71.4% (95%CI, 54.7-88.2)/ 40.4% (95%CI, 26.4-54.5) and 18.1% (95%CI, 10.5-28.1)/ 90.4% (95%CI, 85.5-94.0), respectively. CONCLUSIONS/SIGNIFICANCE: The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

Correlation between HIV viral load and aminotransferases as liver damage markers in HIV infected naive patients: a concordance cross-sectional study.

Abnormalities in liver function tests could be produced exclusively by direct inflammation in hepatocytes, caused by the human immunodeficiency virus (HIV). Mechanisms by which HIV causes hepatic damage are still unknown. Our aim was to determine the correlation between HIV viral load, and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as markers of hepatic damage in HIV naive infected patients. We performed a concordance cross-sectional study. Patients with antiviral treatment experience, hepatotoxic drugs use or co-infection were excluded. We used a Pearson's correlation coefficient to calculate the correlation between aminotransferases serum levels with HIV viral load. We enrolled 59 patients, 50 men and 9 women seen from 2006 to 2008. The mean (+/- SD) age of our subjects was 34.24 +/- 9.5, AST 37.73 +/- 29.94 IU/mL, ALT 43.34 +/- 42.41 IU/mL, HIV viral load 199,243 +/- 292,905 copies/mL, and CD4+ cells count 361 +/- 289 cells/mm(3). There was a moderately strong, positive correlation between AST serum levels and HIV viral load (r = 0.439, P < 0.001); and a weak correlation between ALT serum levels and HIV viral load (r = 0.276, P = 0.034); after adjusting the confounders in lineal regression model the correlation remained significant. Our results suggest that there is an association between HIV viral load and aminotransferases as markers of hepatic damage; we should improved recognition, diagnosis and potential therapy of hepatic damage in HIV infected patients.

Comorbidities and polypharmacy among HIV-positive patients aged 50 years and over: a case-control study.

OBJECTIVE: This study was to determine and compare the prevalences of polypharmacy and comorbidities in patients aged 50 years or older with those patients younger than 50 years in a Mexican population. RESULTS: One hundred and twenty-five patients were enrolled, 60 (48%) were aged 50 years or older. The median CD4+ cell counts were 509 cells/µL (interquartile range [IQR]: 324-730) for the older patients and 384 cells/µL (IQR: 262-562) (P = 0.021) for the younger patients. Viral suppression were significantly higher in the older group: 80% vs. 63% (P = 0.037). The number of comorbidities was significantly higher in the older group, with a median of 2 (IQR: 2-3) vs. 1 (IQR: 0-1) (P ≤ 0.001). After adjustment of the logistic regression model in the older group, the following comorbidities differed between the age groups: systemic arterial hypertension (odds ratio [OR]: 15.75; 95% confidence interval [CI] 3.49-71.05; P = < 0.001), diabetes mellitus (OR: 14.36; 95% CI 1.79-115.07; P = 0.001), osteoarthritis (OR: 10.33; 95% CI 2.88-37.05; P = < 0.001), hyperlipidemia (OR: 2.78; 95% CI 1.22-6.34; P = 0.001), and polypharmacy (OR: 6.58; 95% CI 3.01-14.39; P = 0.001).

Mexican patients with HIV have a high prevalence of vertebral fractures.

Low bone mineral density (BMD) and fragility fractures are common in individuals infected with HIV, who are undergoing antiretroviral therapy (ART). In high-income countries, dual energy X-ray absorptiometrry is typically used to evaluate osteopenia or osteoporosis in HIV infected individuals. However, this technology is unavailable in low andmiddle income countries, so a different approach is needed. The aim of this study was to use X-ray scans of the spine to determine the prevalence of and associated risk factors for vertebral fractures in HIVinfected patients in a tertiary-care hospital in Mexico. We conducted a cross-sectional study of outpatients who were >40 years old and receiving ART at the Hospital de Infectología, La Raza National Medical Center in Mexico City, Mexico. We used semi-quantitative morphometric analysis of centrally digitized X-ray images to assess vertebral deformities in the spine. Anterior, middle and posterior vertebral heights were measured, and height ratios were calculated. For each vertebral body, fractures were graded on the basis of height ratio reductions, and a spine deformity index' (SDI) value was calculated by summing the grades of the vertebral deformities: An SDI>1 was indicative of a vertebral fracture. We included 104 patients, 87% of whom were men. The median age was 49 years [interquartile range (IQR) 42-52]. The most common stage of HIV infection, as defined by the Centers for Disease Control, was B2 in 40 (39%) of patients. Forty seven (45%) patients were on ART regimens that included protease inhibitors (PIs) and 100 (96%) being treated with tenofovir. The median time of ART was 6.5 years (IQR 1.6-9.0). Of the 104 patients in our study, 83 (80%) had undetectable viral load, as assessed by HIV-1 RNA levels, 32 (31%) showed evidence of a previous fracture, 4 (4%) were co-infected with hepatitis C virus, and 57 (55%) had a history of corticosteroid treatment. The prevalence of vertebral fractures was 25%, 95% confidence interval 17-34%. We assessed whether gender, HCV co-infection, previous corticosteroid use, AIDS, total HIV viral load, and current and previous use of PIs were associated with fractures in our study group, but we did not observe a significant association between any of these factors and vertebral fractures. The prevalence of vertebral fractures was high among HIV-infected patients. We propose that screening for bone disease should be performed in HIV individuals who are at risk of fragility fractures. Furthermore, we suggest that X-ray based assessment of the spine should be considered in patients who are at increased risk of fragility fractures, irrespective of BMD levels, particularly in elderly patients in low and middle income countries.

Diagnostic accuracy cohort study and clinical value of the Histoplasma urine antigen (ALPHA Histoplasma EIA) for disseminated histoplasmosis among HIV infected patients: A multicenter study.

BACKGROUND: The Histoplasma urine antigen (HUAg) is the preferred method to diagnose progressive disseminated histoplasmosis (PDH) in HIV patients. In 2007, IMMY ALPHA Histoplasma EIA was approved for clinical for on-site use, and therefore useful for regions outside the United States. However, ALPHA-HUAg is considered inferior to the MVista-HUAg which is only available on referral. We aim to evaluate the diagnostic accuracy of ALPHA-HUAg. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multicenter, prospective, diagnostic test study in two secondary and eight tertiary-care facilities in Mexico. We included HIV patient with PDH suspicion and evaluated ALPHA-HUAg diagnostic accuracy using as reference standard the Histoplasma capsulatum growth on blood, bone marrow, and tissue cultures or compatible histopathologic exam (PDH-proven). We evaluated the results of 288 patients, 29.5% (85/288; 95% confidence interval [CI], 24.3-35.1) had PDH. The sensitivity of ALPHA-HUAg was 67.1% (95% CI, 56-76.8%) and the specificity was 97.5% (95% CI, 94.3%-99.1%). The positive likelihood ratio was 27.2 (95% CI; 11.6-74.4). In 10.5% of the PDH-proven patients, a co-existing opportunistic infection was diagnosed, mostly disseminated Mycobacterium avium complex infection. CONCLUSIONS/SIGNIFICANCE: We observed a high specificity but low sensitivity of IMMY-HUAg. The test may be useful to start early antifungals, but a culture-based approach is necessary since co-infections are frequent and a negative IMMY-HUAg result does not rule out PDH.

Effectiveness and Risk Factors for Virological Outcome of Raltegravir-Based Therapy for Treatment-Experienced HIV-Infected Patients.

OBJECTIVE: We evaluated the effectiveness of a raltegravir (RAL)-containing regimen plus an optimized background regimen in HIV-1 highly treatment-experienced patients. DESIGN: A retrospective cohort, multicentre study was conducted. METHODS: Adult (>16 years old) HIV treatment-experience patients starting therapy with a RAL-containing regimen were included. Effectiveness was evaluated as the percentage of patients with an undetectable HIV-1 RNA viral load (<50 and <200 copies/mL) after 48 weeks, and changes in CD4+ cell counts. We evaluated the risk factors associated with treatment failure. RESULTS: Of the 107 patients in the cohort, 86% were men, the median age was 45 years [interquartile range (IQR) 40-52] and the median number of previous regimens was six (IQR 4-7). After 48 weeks of treatment, 73% (IQR 63-80%) of patients (n = 78) had a viral load of <50 copies/mL and 85% (IQR 77-90%) (n = 91) had <200 copies/mL. In a logistic regression model, risk factors associated with a virological outcome of HIV-1 RNA of <200 copies/mL were age >40 years [odds ratio (OR) 5.61; 95% confidence interval (CI) 1.61-18.84; P = 0.006] and use of tenofovir in the regimen (OR 0.16; 95% CI 0.03-0.80; P = 0.026). CONCLUSIONS: In this Mexican cohort, RAL achieved high rates of virological suppression and an increase in CD4+ cell count in highly treatment-experienced patients infected with HIV-1. Age >40 years was associated with a good virological outcome, contrary to tenofovir use, which was associated with a poor virological outcome.