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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.

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., Author summary Histoplasmosis, an infection caused by Histoplasma capsulatum, is prevalent in the Americas, it is a common cause of pulmonary acute disease in cave explorers, speleologists, boy scouts and some other people in circumstantial risk, in most of these people the infection is commonly self-limited. However, in people living with HIV (PLWHIV) this infection might be acquired without specific exposition and it behaves like a severe disease with high fever, consumption, septic shock and death. Thus, there is a need for rapid and accurate methods for diagnosis in this population at risk. We tested five different methods for rapid diagnosis (three based on antigen detection in urine and two molecular assays based on PCR amplification, widely used) of disseminated histoplasmosis and we were able to demonstrate that two urine antigen detection tests (clarus Histoplasma GM Enzyme Immunoassay kit and MiraVista Histoplasma Urine Antigen LFA) showed excellent performance to diagnose of disseminated histoplasmosis in PLWHIV. The antigen detection tests have advantages over the PCR tests, their performance is higher, they are commercial standardized tests, easy to perform, and provide results in hours, therefore the integration of these tests in clinical laboratories will certainly impact on early diagnosis/treatment and consequently on the outcome of patients.

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.

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., Author summary Histoplasmosis is an endemic mycosis in many regions of Latin America. In the HIV population it manifests as progressive disseminated histoplasmosis (PDH), an entity hard to diagnose since the causative fungi—Histoplasma capsulatum—is slow growing and requires advance biosafety for its handling. As an alternative, the diagnosis can be made by detecting the histoplasma urinary antigen, but only one kit is commercially available outside the US. We evaluated this kit (IMMY ALPHA Histoplasma EIA) among HIV patients with suspected and found a high specificity but low sensitivity (i.e., a positive histoplasma urine antigen is almost unequivocal, but a negative result does not rule out the PDH). However, we believe the test is useful since the positive likelihood rates show that a patient with PDH is 27 times more likely to have an IMMY-HUAg positive result; this may allow early targeted treatment.

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 and-middle 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 HIV-infected 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]. Themost 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 (IQR1.6-9.0). 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.

There are many new drugs for HCV treatment. First generation protease inhibitors are about to be discontinued. However in developing countries the likelihood of access to these new drugs is vague. As in other poor countries, in Mexico we only have peg interferon and ribavirin for HCV treatment and the costs of the new therapies are hard to fill. This is a report of the outcome in 30 patients who received triple therapy adding Boceprevir to peg interferon and Ribavirin as part of an extended-access program. As described elsewhere Latinos have lower response rates. This is the largest series of cases in Mexico City, and we would like to share this experience with other developing countries.

AIM To evaluate the aspartate aminotransferase (AST) to platelet ratio index (APRI) as a predictive factor of early viral response in chronic hepatitis C naive patients. METHODS We performed an ambispective case-control study. We enrolled chronic hepatitis C naive patients who were evaluated to start therapy with PEGylated interferon alpha-2b (1.5 mug/kg per week) and ribavirin (> 75 kg: 1200 mg and < 75 kg: 1000 mg). Patients were allocated into two groups, group 1: Hepatitis C patients with early viral response (EVR), group 2: Patients without EVR. Odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the relationship between each risk factor and the EVR in both groups. RESULTS During the study, 80 patients were analyzed, 45 retrospectively and 35 prospectively. The mean +/- SD age of our subjects was 42.9 +/- 12 years; weight 70 kg (+/- 11.19), AST 64.6 IU/mL (+/- 48.74), alanine aminotransferase (ALT) 76.3 IU/mL (+/- 63.08) and platelets 209 000 mill/mm(3) (+/- 84 429). Fifty-five (68.8%) were genotype 1 and 25 (31.3%) were genotype 2 or 3; the mean hepatitis C virus RNA viral load was 2 269 061 IU/mL (+/- 7 220 266). In the univariate analysis, APRI was not associated with EVR [OR 0.61 (95% CI 0.229-1.655, P = 0.33)], and the absence of EVR was only associated with genotype 1 [OR 0.28 (95% CI 0.08-0.94, P = 0.034)]. After adjustment in a logistic regression model, genotype 1 remains significant. CONCLUSION APRI was not a predictor of EVR in chronic hepatitis C; Genotype 1 was the only predictive factor associated with the absence of EVR in our 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 (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.