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.

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.

Presence of rare hepatitis C virus subtypes, 2j, 2k, and 2r in Mexico City as identified by sequencing.

The HCV 5'UTR, Core/E1, and NS5B regions of samples from fifty patients infected with the hepatitis C virus (HCV) were analyzed. Seventeen patients were identified with genotype (GT) 1b, eleven with GT-1a, nine with GT-2b and four with GT-3a. Two rare subtypes were detected: GT-2j in two patients and GT-2r in one patient. Three patients had mixed infections: one with GT-2k + 2j and two with GT-1b + 2b. This work identifies HCV GTs, 2j, 2k, and 2r for the first time in Mexico.

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.

Relationship between the Viral Load in Patients with Different COVID-19 Severities and SARS-CoV-2 Variants.

SARS-CoV-2 has spread throughout the world since 2019, changing in its genome and leading to the appearance of new variants. This gave it different evolutionary advantages, such as greater infectivity and/or a greater ability to avoid the immune response, which could lead to an increased severity of COVID-19 cases. There is no consistent information about the viral load that occurs in infection with the different SARS-CoV-2 variants, hence, in this study we quantify the viral load of more than 16,800 samples taken from the Mexican population with confirmed diagnosis of COVID-19 and we analyze the relation between different demographic and disease variables. We detected that the viral load caused by different variants differs only in the first two days after the onset of symptoms, being higher when infections are caused by the delta variant and lower when caused by omicron. Furthermore, the viral load appears to be higher in outpatients compared to hospitalized patients or in cases of death. On the other hand, no differences were found in the viral load produced in vaccinated and unvaccinated patients, nor did it differ between genders.

Omicron-BA.1 Dispersion Rates in Mexico Varied According to the Regional Epidemic Patterns and the Diversity of Local Delta Subvariants.

PURPOSE: The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In this work, a characterization of the spread of this variant in Mexico is presented. METHODS: The time to fixation of BA.1, the diversity of Delta sublineages, the population density, and the level of virus circulation during the inter-wave interval were determined to analyze differences in BA.1 spread. RESULTS: BA.1 began spreading during the first week of December 2021 and became dominant in the next three weeks, causing the fourth COVID-19 epidemiological surge in Mexico. Unlike previous variants, BA.1 did not exhibit a geographically distinct circulation pattern. However, a regional difference in the speed of the replacement of the Delta variant was observed. CONCLUSIONS: Viral diversity and the relative abundance of the virus in a particular area around the time of the introduction of a new lineage seem to have influenced the spread dynamics, in addition to population density. Nonetheless, if there is a significant difference in the fitness of the variants, or if the time allowed for the competition is sufficiently long, it seems the fitter virus will eventually become dominant, as observed in the eventual dominance of the BA.1.x variant in Mexico.

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.

Impact of the introduction of chikungunya and zika viruses on the incidence of dengue in endemic zones of Mexico.

BACKGROUND: With the arrival of chikungunya (CHIKV) and zika (ZIKV) viruses in Mexico, there was a decrease in diagnosed dengue virus (DENV) cases. During the first years of cocirculation (2015-2017), the algorithms established by epidemiological surveillance systems and the installed capacity limited us to one diagnostic test per sample, so there was an underestimation of cases until September 2017, when a multiplex algorithm was implemented. Therefore, the objective of this study was determine the impact of the introduction of CHIKV and ZIKV on the incidence of diagnosed DENV in endemic areas of Mexico, when performing the rediagnosis, using the multiplex algorithm, in samples from the first three years of co-circulation of these arboviruses. METHODOLOGY AND PRINCIPAL FINDINGS: For this, 1038 samples received by the Central Laboratory of Epidemiology between 2015 and 2017 were selected for this work. Viruses were identified by multiplex RT-qPCR, and the χ2 test was used to compare categorical variables. With the new multiplex algorithm, we identified 2.4 times the rate of arbovirosis as originally reported, evidencing an underestimation of the incidence of the three viruses. Even so, significantly less dengue was observed than in previous years. The high incidence rates of chikungunya and Zika coincided with periods of dengue decline. The endemic channel showed that the cases caused by DENV rose again after the circulation of CHIKV and ZIKV decreased. In addition, 23 cases of coinfection were identified, with combinations between all viruses. CONCLUSIONS AND SIGNIFICANCE: The results obtained in this study show for the first time the real impact on the detected incidence of dengue after the introduction of CHIKV and ZIKV in Mexico, the degree of underestimation of these arboviruses in the country, as well as the co-infections between these viruses, whose importance clinical and epidemiological are still unknown.

[Coinfections by SARS-CoV-2 and other respiratory viruses and their clinical outcome]. / Coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico.

Background: SARS-CoV-2 is a coronavirus described for the first time in China, in December 2019. This virus can cause a disease with a very variable spectrum that ranges from asymptomatic cases to deaths. The most severe cases are normally associated with comorbidities and with the age of the patient. However, there are patients who are not part of these risk groups and develop severe cases. Objetive: To determine the association between coinfections by SARS-CoV-2 and other respiratory viruses and their clincal outcome. Material and methods: RT-qPCR was performed to determine the presence of 16 respiratory viruses in 103 confirmed COVID-19 cases. Demographic and comorbid data were collected, and statistical analyzes were performed to determine associations with severity. Results: Of the 103 analyzed cases, 14 (13.6%) presented a coinfection, of these, 92% did not require hospitalization, even in those cases in which the patient presented advanced age and some comorbidities. Conclusions: These results suggest that coinfection of SARS-CoV-2 and other respiratory viruses is not related to a more severe form of COVID-19 and, in some cases, depending on the virus involved, it could even lead to a better prognosis. These findings lay the foundations for the development of new studies that could determine the biological mechanism of this phenomenon.

Introducción: el SARS-CoV-2 es un coronavirus que fue descrito por primera vez en diciembre de 2019 en Wuhan, China. Este virus causa una enfermedad que varía en un espectro de severidad que va desde casos asintomáticos hasta defunciones. Los casos más severos se asocian normalmente con algunas comorbilidades y con la edad del paciente. Sin embargo, existen pacientes que no son parte de estos grupos de riesgo y aun así desarrollan casos graves. Objetivo: determinar la asociación entre las coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico. Material y métodos: se realizó RT-qPCR para determinar la presencia de 16 virus respiratorios en 103 casos confirmados de COVID-19. Se recolectaron datos demográficos y de comorbilidades, y se realizaron análisis estadísticos para determinar asociaciones con gravedad. Resultados: el 13.6% de los casos (14/103) presentaron alguna coinfección, de estos, el 92% nunca requirió ingreso hospitalario, aun en aquellos casos en los que el paciente presentara comorbilidades y edad avanzada. Conclusiones: estos resultados sugieren que la coinfección no está relacionada con un COVID-19 más grave y que, dependiendo del virus involucrado, incluso podría conducir a un mejor pronóstico. Estos hallazgos sientan las bases para nuevos estudios dirigidos a determinar el mecanismo biológico por el cual ocurre este fenómeno y a proponer las estrategias correspondientes para limitar la progresión a casos severos de COVID-19.

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).

Effect of branched-chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients.

The incidence rate of insulin resistance (IR) in patients with chronic hepatitis C (CHC) is high. Recently, branched-chain amino acids (BCAA) have been shown to attenuate IR in CHC patients; however, their effect on patient quality of life remains unclear. Therefore, the aim of the current prospective study was to determine the effects of BCAA supplement on IR and health-related quality of life (HR-QoL) in patients with CHC. In the study, 20 non-diabetic patients with CHC, who were non-responders to peginterferon-α and ribavirin, were recruited. Patients took a BCAA supplement once a day (30 g, after a minimum 10-h overnight fast) for 3 months. Serum levels of glucose, insulin, albumin, triglycerides and cholesterol were measured at 0 and 3 months. Additionally, IR was measured using the Homeostasis Model Assessment-IR, HR-QoL was assessed using the 36-item Short Form Health Survey and viral load was measured by reverse transcription polymerase chain reaction using Taqman probes. The Wilcoxon signed-rank test was used to determine statistical significance. The results indicated that 70% of the subjects were positive for IR, which decreased to 50% by the end of the study; furthermore, 85% of the subjects demonstrated some level of improvement. Overall, the BCAA treatment significantly decreased IR (P=0.006) and augmented serum albumin concentration (P=0.008) compared with basal values. Additionally, by the end of the treatment, viral load and triglycerides levels had decreased, though these results were not significant (P=0.084 and P=0.080, respectively). BCAA treatment also improved HR-QoL regarding role limitations due to physical health problems (P=0.017), role limitations due to emotional problems (P=0.026) and social function (P=0.008). In conclusion, BCAA supplementation reduced IR and improved HR-QoL in patients with CHC. These findings support the application of IR therapy as a possible therapeutic strategy for hepatitis C infection.

Coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico / Coinfections by SARS-CoV-2 and other respiratory viruses and their clinical outcome

Introducción: el SARS-CoV-2 es un coronavirus que fue descrito por primera vez en diciembre de 2019 en Wuhan, China. Este virus causa una enfermedad que varía en un espectro de severidad que va desde casos asintomáticos hasta defunciones. Los casos más severos se asocian normalmente con algunas comorbilidades y con la edad del paciente. Sin embargo, existen pacientes que no son parte de estos grupos de riesgo y aun así desarrollan casos graves. Objetivo: determinar la asociación entre las coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico. Material y métodos: se realizó RT-qPCR para determinar la presencia de 16 virus respiratorios en 103 casos confirmados de COVID-19. Se recolectaron datos demográficos y de comorbilidades, y se realizaron análisis estadísticos para determinar asociaciones con gravedad. Resultados: el 13.6% de los casos (14/103) presentaron alguna coinfección, de estos, el 92% nunca requirió ingreso hospitalario, aun en aquellos casos en los que el paciente presentara comorbilidades y edad avanzada. Conclusiones: estos resultados sugieren que la coinfección no está relacionada con un COVID-19 más grave y que, dependiendo del virus involucrado, incluso podría conducir a un mejor pronóstico. Estos hallazgos sientan las bases para nuevos estudios dirigidos a determinar el mecanismo biológico por el cual ocurre este fenómeno y a proponer las estrategias correspondientes para limitar la progresión a casos severos de COVID-19.

Background: SARS-CoV-2 is a coronavirus described for the first time in China, in December 2019. This virus can cause a disease with a very variable spectrum that ranges from asymptomatic cases to deaths. The most severe cases are normally associated with comorbidities and with the age of the patient. However, there are patients who are not part of these risk groups and develop severe cases. Objetive: To determine the association between coinfections by SARS-CoV-2 and other respiratory viruses and their clincal outcome. Material and methods: RT-qPCR was performed to determine the presence of 16 respiratory viruses in 103 confirmed COVID-19 cases. Demographic and comorbid data were collected, and statistical analyzes were performed to determine associations with severity. Results: Of the 103 analyzed cases, 14 (13.6%) presented a coinfection, of these, 92% did not require hospitalization, even in those cases in which the patient presented advanced age and some comorbidities. Conclusions: These results suggest that coinfection of SARS-CoV-2 and other respiratory viruses is not related to a more severe form of COVID-19 and, in some cases, depending on the virus involved, it could even lead to a better prognosis. These findings lay the foundations for the development of new studies that could determine the biological mechanism of this phenomenon.