RESUMEN

Integrase strand transfer inhibitors (INSTI) are associated with neuropsychiatric adverse events (NPAEs). The aim of this study was to evaluate improvements in NPAEs after switching an INSTI-based regimen to darunavir/cobicistat (DRV/c) or doravirine (DOR). Methods: A prospective cohort study was conducted to evaluate the reversibility of NPAEs via the Patient Health Questionnaire (PHQ-9), the Insomnia Severity Index (ISI), and the Hospital Anxiety and Depression Scale (HADS-A and D) in patients who started antiretroviral therapy with dolutegravir (DTG) or bictegravir (BIC). These patients were switched to DRV/c or DOR. Scales were compared at the moment of the switch and 12 weeks later. Results: We included 1153 treatment-naïve men, 676 (58.7%) with BIC and 477 (41.3%) with DTG. A total of 32 (2.7%) experienced NPAEs that led to discontinuation. Insomnia was found in 20 patients; depression via PHQ-9 in 21 patients, via HADS-D in 5 patients, and anxiety via HADS-A in 12 patients. All of them were evaluated by a psychiatrist at the moment of the symptoms; 7 (21.8%) started psychotropic drugs. After 12 weeks of follow-up, PHQ-9, ISI, HADS-A, and HADS-D decreased, with a p-value ≤ 0.05. Conclusions: NPAEs seem to improve after switching to a DRV/c- or DOR-based regimen after the first 4 and 12 weeks.

Asunto(s)

Cobicistat , Darunavir , Infecciones por VIH , Piridonas , Humanos , Masculino , Darunavir/efectos adversos , Darunavir/uso terapéutico , Darunavir/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Cobicistat/efectos adversos , Cobicistat/uso terapéutico , Cobicistat/administración & dosificación , Piridonas/efectos adversos , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de Integrasa VIH/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamente , Sustitución de Medicamentos/efectos adversos , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Piperazinas/efectos adversos , Triazoles

RESUMEN

OBJECTIVE: To describe clinical, microbiological and echocardiographic aspects of endocarditis in a specific group of patients without intracardiac devices or underlying structural heart disease. METHOD: Retrospective study, clinical records and echocardiographic reports were reviewed during the period 1997 to 2020. Duke's modified criteria were applied. Statistical analysis: univariate expressed in frequencies, using measures of dispersion and central tendency. RESULTS: 30,000 echocardiographic reports were reviewed, only 1350 had infectious endocarditis as a reason for sending, of which 248 cases were selected. The mean age was 48.1 ± 16.7 years. 140 men (56%) and 108 women (44%). The most frequent echocardiographic sign was vegetation, in 278 (93.60%), and most common location was mitral (35.55%), with a higher number of cases in the right ventricle than expected. The most common systemic disease was kidney disease, in 135 (41.08%). A case of Streptococcus thoraltensis not previously reported in Mexico was identified. CONCLUSIONS: The presence of infectious endocarditis has increased due to invasive in-hospital and drug procedures. Due to their complexity, multidisciplinary teams are indispensable.

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OBJETIVO: Describir aspectos clínicos, microbiológicos y ecocardiográficos de endocarditis en un grupo específico de pacientes sin dispositivos intracardiacos ni cardiopatía estructural subyacente. MÉTODO: Estudio retrospectivo en el que se revisaron expedientes clínicos y reportes ecocardiográficos durante el periodo de 1997 a 2020. Se aplicaron los criterios modificados de Duke. Se describió la muestra por edad, sexo, enfermedad sistémica, vegetaciones y agente microbiológico. Se excluyeron pacientes con cardiopatía estructural o Libman-Sacks. Análisis estadístico: univariado expresado en frecuencias, utilizando medidas de dispersión y tendencia central. RESULTADOS: Se revisaron 30,000 reportes ecocardiográficos, de los cuales solo 1350 tenían como motivo de envío endocarditis infecciosa, y de estos se seleccionaron 248 casos. La edad promedio fue de 48.1 ± 16.7 años. Hubo 140 hombres (56%) y 108 mujeres (44%). El signo ecocardiográfico más frecuente fue la vegetación, en 278 (93.60%), y la ubicación más común fue mitral (35.55%), con un número mayor de casos en el ventrículo derecho de lo esperado. La enfermedad sistémica más común fue la enfermedad renal, en 135 (41.08%). Se identificó un caso de Streptococcus thoraltensis no reportado previamente en México. CONCLUSIONES: La presencia de endocarditis infecciosa ha aumentado debido a procedimientos invasivos intrahospitalarios y fármacos. Por su complejidad, los equipos multidisciplinarios son indispensables.

Asunto(s)

Endocarditis , Cardiopatías , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Cardiopatías/diagnóstico por imagen , Cardiopatías/epidemiología , Cardiopatías/etiología , Endocarditis/diagnóstico por imagen , Endocarditis/epidemiología , Ecocardiografía , Hospitales

RESUMEN

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.

Asunto(s)

Fármacos Anti-VIH , Infecciones por VIH , Hipertrigliceridemia , Transportador 1 de Casete de Unión a ATP/genética , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Apolipoproteína A-V/genética , Apolipoproteína C-III/genética , Estudios de Casos y Controles , Proteínas de Transferencia de Ésteres de Colesterol/genética , Genotipo , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Humanos , Hipertrigliceridemia/inducido químicamente , Hipertrigliceridemia/genética , México , Polimorfismo de Nucleótido Simple , Proteínas Quinasas , Triglicéridos

RESUMEN

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.

Asunto(s)

Antígenos Fúngicos/orina , Infecciones por VIH/complicaciones , VIH-1 , Histoplasmosis/complicaciones , Adulto , Femenino , Infecciones por VIH/epidemiología , Histoplasma/inmunología , Histoplasma/metabolismo , Histoplasmosis/epidemiología , Histoplasmosis/orina , Humanos , Técnicas para Inmunoenzimas , Masculino , México/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto Joven

RESUMEN

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.

Asunto(s)

Técnicas de Genotipaje/métodos , Hepacivirus/genética , Hepatitis C/virología , ARN Viral , Análisis de Secuencia de ARN/métodos , Proteínas no Estructurales Virales/genética , Estudios Transversales , Humanos , México

RESUMEN

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).

Asunto(s)

Comorbilidad , Seropositividad para VIH/tratamiento farmacológico , Polifarmacia , Adulto , Estudios de Casos y Controles , Seropositividad para VIH/epidemiología , Humanos , Persona de Mediana Edad , Prevalencia

RESUMEN

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.

Asunto(s)

Pruebas Diagnósticas de Rutina/métodos , Infecciones por VIH/complicaciones , Histoplasmosis/diagnóstico , Adulto , Antígenos Fúngicos , Femenino , Histoplasma , Histoplasmosis/etiología , Humanos , Masculino , México , Estudios Prospectivos

RESUMEN

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.