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.

[Tuberculosis caused by Mycobacterium bovis, a re-emerging infection?] / Tuberculosis por Mycobacterium bovis: ¿una infección reemergente?

Currently, tuberculosis (TB) is a public health problem, is present in all regions of the world and remains one of the most deadly communicable diseases, particularly associated with infection by the human immunodeficiency virus (HIV). Cases of TB Mycobacterium bovis more and more frequent, especially in vulnerable populations. TB caused by M. bovis clinical, radiological and histologically indistinguishable from tuberculosis caused by M. tuberculosis; however, there are some differences that make M. tuberculosis particular. The direct correlation between infection with M. bovis in cattle and human disease has been well documented, but the true prevalence is underestimated. Overall, the proportion of cases of human TB caused by M. bovis is low compared with M. tuberculosis, but its potential in the groups most at risk impact should not be underestimated by the impact on morbidity and mortality.

Actualmente, la tuberculosis (TB) es un problema de salud pública que está presente en todas las regiones del mundo y sigue siendo una de las enfermedades transmisibles más mortales, sobre todo asociada a la infección por el virus de la inmunodeficiencia humana (VIH). Los casos de TB por Mycobacterium bovis cada vez son más frecuentes, principalmente en poblaciones vulnerables. La TB causada por M. bovis es clínica, radiológica e histológicamente indistinguible de la tuberculosis causada por M. tuberculosis; sin embargo, existen algunas diferencias respecto a M. tuberculosis que la hacen particular. La correlación directa entre la infección por M. bovis en el ganado vacuno y la enfermedad en humanos ha sido bien documentada, aunque la prevalencia real es subestimada. En general, la proporción de casos de TB humana a causa de M. bovis es baja en comparación con M. tuberculosis, pero su impacto potencial en los grupos de mayor riesgo no debería subestimarse por la repercusión en la morbilidad y mortalidad.

Effectiveness of etravirine-based therapy for treatment-experienced HIV-infected patients.

INTRODUCTION: Treatment options are limited for HIV-1-infected individuals who have received extensive previous antiretroviral therapy. ETV has shown significant clinical benefits in treatment-experienced HIV-1+ patients with antiretroviral resistance. The aim of this study was to evaluate the effectiveness of ETV plus optimized background regimen in real-life conditions in a cohort of highly HIV-1 antiretroviral-experienced patients. METHODOLOGY: Retrospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ETV-containing regimen. The effectiveness was evaluated using HIV-1 RNA viral load and changes in CD4+ cell count after 48 weeks of treatment. RESULTS: Forty-two patients ≥ 16 years of age were included; 74% were men, and the median age was 45 years (IQR 41-53). All participants had prior non-nucleoside reverse transcriptase inhibitor use (55% nevirapine, 83%, efavirenz, and 28% both). Baseline median HIV-1 RNA viral load was 15,598 copies/mL (IQR 2651-84,175) and CD4+ cell count was 276 cells/mL (IQR 155-436). After 48 weeks of treatment, 90.5% (95% CI 78-96) of patients had HIV-1 RNA viral load < 200 copies/mL and 76% (95% CI 61-86) had < 50 copies/mL. CD4+ cell counts increased from baseline to 48 weeks of treatment to a median of 407 cells/mL (IQR 242-579); p < 0.001. Virological outcome was associated with virological failure at baseline HIV-1 RNA viral load ≥ 100,000 copies/mL (OR 7.6; 95% CI 1.2-44.80; p = 0.025). CONCLUSIONS: Our study provides clinically important evidence of the effectiveness and safety of ETV in highly antiretroviral-experienced HIV-1-infected patients.

Anal intraepithelial neoplasia among HIV-positive men who have sex with men.

Neoplasia is the second most common cause of mortality in HIV patients. The prevalence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of antiretroviral therapy. We screened 94 HIV-infected MSM patients. We found high-grade squamous intraepithelial lesions (HSIL) in six of the patients. The calculated prevalence of HSIL was 6.4% (95% confidence interval: 2.9-13.2). The study and implementation of screening programs for high-risk groups is a priority.

Risk factors associated with mortality in patients infected with influenza A/H1N1 in Mexico.

BACKGROUND: Influenza virus pandemics vary dramatically in their severity and mortality. Thus, it is very important to identify populations with high risks of developing severe illness to reduce mortality in future pandemics. The purpose was to determine the mortality-associated risk factors in hospitalized Mexican patients infected with influenza A/H1N1. RESULTS: The risk factors associated with mortality were: male sex [odds ratio (OR) = 5.25, confidence interval (CI) = 1.22-28.95], medical attention delayed >3 days (OR = 9.9, CI = 1.51-64.52), anti-flu therapy delayed >3 days (OR = 10.0, CI = 1.07-93.43), admission to intensive care unit (ICU) (OR = 9.9, CI = 1.51-64.52) and creatinine levels >1.0 mg/dL when admitted to hospital (OR = 11.2, CI = 1.05-120.32). After adjusting for the effects of potentially confounding variables in a logistic regression model, delayed medical attention (OR = 13.91, CI = 1.09-41.42, p = 0.044) and ICU hospitalization (OR = 11.02, CI = 1.59-76.25, p = 0.015) were the only predictors of mortality. CONCLUSION: Early medical attention is essential for reducing the mortality risk in patients with influenza A/H1N1, while a requirement for ICU management increases the risk.

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.

Proximal renal tubular dysfunction related to antiretroviral therapy among HIV-infected patients in an HIV clinic in Mexico.

Proximal renal tubular dysfunction (PRTD) of varying severity has been associated with antiretroviral toxicity, especially related to the use of tenofovir (TDF). The aim of this study was to investigate whether HIV-infected patients who use a tenofovir-based regimen are at increased risk of tubular dysfunction. We conducted an observational, comparative, longitudinal, prospective study. Estimated glomerular filtration rate (eGFR) and markers of tubular damage to assess tubular dysfunction (fractional excretion of phosphate and uric acid, glycosuria, and proteinuria) were measured at baseline and at weeks 12 and 24. Of 111 participants, PRTD was found in 6.3% at week 12 and 9% at week 24, with no statistically significant difference between those on an abacavir (ABC)-containing regimen or a TDF-containing regimen. We also found an increase in triglycerides associated with the ABC-containing regimen compared with the TDF group. The use of an ABC- or TDF-containing regimen was independently associated with tubular dysfunction, but we found no significant differences between these groups, except when TDF was combined with a protease inhibitor. A better and more complete assessment of renal function is needed, because the presence of tubular dysfunction and proteinuria without impairment of eGFR may affect the renal safety of HIV-infected patients.

Intensification of treatment with pegylated interferon alfa in patients coinfected with HIV and HBV genotype H or G being treated with a tenofovir/emtricitabine-containing regimen.

BACKGROUND/AIMS: The most common HBV genotypes in HIV-coinfected patients in Mexico are H and G; the response to treatment for these genotypes is unknown. The aim of the study was to examine the effectiveness of intensification with pegylated interferon (PEG-IFN) alfa-2a or alfa-2b in HBV/HIV-coinfected patients treated with a tenofovir/emtricitabine (TDF/FTC) backbone in an HIV clinic in Mexico City. METHODOLOGY: We performed a single-arm open-label trial involving HBV/HIV-coinfected patients. Patients with chronic hepatitis B who were HBeAg positive were treated with TDF/FTC-containing regimen. Treatment was intensified by addition of PEG-IFN alfa-2b or alfa-2a for 24 weeks. The primary endpoint of effectiveness, assessed after 24 weeks, was suppression of HBV DNA to <60 IU/mL. RESULTS: We enrolled 29 patients; 27 (93%) were men. HBV genotypes were F in 2 (6.9%), A in 2 (6.9%), G in 10 (34.5%), and H in 15 (51.7%). The primary endpoint was present in 17 (58%) patients (95% CI 29.7%­70.8%). CONCLUSIONS: Intensification with PEG-IFN alfa-2a or alfa-2b is effective and well tolerated in patients with chronic hepatitis B who are HBeAg positive, have genotype H or G, and are coinfected with HIV while they are being treated with TDF/FTC-containing regimen.

APRI as a predictor of early viral response in chronic hepatitis C patients.

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.