The Emergence of Hepatitis C Virus Genotype 4d Among Human Immunodeficiency Virus-Infected Patients in Mexico City: A Molecular Epidemiological Study.

ABSTRACT: The recent detection of hepatitis C virus genotype 4 infection in human immunodeficiency virus-infected patients prompted performing molecular characterization of these isolates. All the Mexican isolates belonged to a subcluster within the 4d group and shared a common ancestor with a French isolate. The estimated timing of introduction in Mexico City was as recent as December 2015.

Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico.

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico.

There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.

Baseline Hepatitis C Virus NS5A Resistance-Associated Polymorphisms in Patients With and Without Human Immunodeficiency Virus Coinfection in Mexico.

Objective: We aimed to evaluate the frequency and associated factors of baseline NS5A resistance-associated substitutions (RASs) in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) monoinfection with genotype 1b (GT1b) or genotype 1a (GT1a). Moreover, we performed a phylogenetic analysis to evaluate the pattern of clustering among samples of patients with RASs. Results: Fifty-five patients were infected with GT1a, of whom 44 (80%) were HIV-infected patients. RAS prevalence in GT1a was 14% (6/44) and distributed as follows: 5 (11%) harbored M28V and 1 (2%) A92T. Twenty-four patients were infected with HCV GT1b, of whom only 5 (21%) were HIV coinfected; RASs were found in 17/24 (71%) patients, as follows: Y93H+F37L+Q54H (1/24), Y93H+F37L (1/24), P58S (1/24), L31F+F37L (1/24), F37L+H/Q54H (3/24), and F37L (10/24). Only GT1b was significantly associated with RASs (adjusted odds ratio 16.37; 95% confidence interval 2.74-97.48; p = 0.002) in the multivariate analysis. A cluster of sequences from HIV/HCV GT1a patients was found; however, we did not find phylogenetic relationships among sequences with NS5A RASs. Conclusions: In our population of HCV-infected patients, the frequency of NS5A RASs at baseline was somewhat similar to the previously reported worldwide rate. HCV GT1b showed the most significant association with harboring of NS5A RASs. Of note, despite there being clusters among sequences of HIV-coinfected patients, NS5A RASs were not transmitted.

Histoplasma panniculitis in a patient with systemic lupus erythematosus.

Histoplasmosis usually presents primarily as lung infection. Occasionally, mainly in immunocompromised hosts, it can spread and cause systemic manifestations. Skin lesions have been reported in 10 to 15 percent of cases of disseminated histoplasmosis, and panniculitis has been described as an unusual form of presentation in affected patients. We present the case of a patient with systemic lupus erythematosus who presented cellulitis due to disseminated histoplasmosis.

Randomized controlled trial of Hepatitis B virus vaccine in HIV-1-infected patients comparing two different doses.

BACKGROUND: Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is not infrequent as both share same route of exposure. The risk of developing chronic hepatitis B virus is 6%, in general population but can reach 10-20% in HBV/HIV co-infected patients. When compared to general population, the response rate to HBV vaccine in HIV-infected patients is diminished, so previous studies have tried to improve this response using variety of schedules, doses and co-administration of immunomodulators. The purpose of this study was to evaluate two doses of recombinant HBV vaccine (10 or 40 microg), IM at 0, 1 and 6 months. Vaccination response was measured 30-50 days after last dose; titers of >9.9 IU/L were considered positive. RESULTS: Seventy-nine patients were included, 48 patients (60.7%) serconverted. Thirty-nine patients (49.3%) received 10 microg vaccine dose, 24 patients (61.5%) seroconverted. Forty patients (50.7%) received 40 microg vaccine dose, 24 (60%) seroconverted. There were no differences between two doses. A statistically significant higher seroconversion rate was found for patients with CD4 cell counts at vaccination > or = 200 cel/mm3 (33 of 38 patients, 86.8%), compared with those with CD4 < 200 cel/mm3 (15 of 41, 36.6%), [OR 11.44, 95% IC 3.67-35.59, p = 0.003], there were no differences between two vaccine doses. Using the logistic regression model, CD4 count <200 cel/mm3 were significantly associated with non serologic response (p = 0.003). None other variables such as gender, age, risk exposure for HIV, viral load, type or duration of HAART or AIDS-defining illness, were associated with seroconversion. CONCLUSION: In this study, an increase dose of HBV vaccine did not show to increase the rate of response in HIV infected subjects. The only significant findings associated to the response rate was that a CD4 count > or = 200 cel/mm3, we suggest this threshold at which HIV patients should be vaccinated.

[Pathogenic mechanisms of HIV infection]. / Mecanismos patogénicos de la infección por VIH.

Despite the recent advances in the understanding of the mechanisms of HIV induced T cell depletion, it has not been possible to elucidate the specific virulence factors and as a consequence to create effective strategies for its eradication. It is mandatory to understand deeply the pathogenetic mechanisms of the HIV infection in order to face possible ways to destroy it. In order to fulfill this goal, we have to understand better important events like primary infection, the differences in progression to AIDS and specially those determinants of the host-virus relationship.

Early HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin.

INTRODUCTION: Currently, interferon alfa and ribavirin are the mainstay of therapy for patients with chronic hepatitis C. Recently the pegylation of interferon has allowed a once weekly application, resulting in an increased sustained viral response rate. The analysis of serum HCV dynamics has been shown to be useful in predicting clinical effects and optimizing the treatment regimen. AIM: The aim of the present study was to assess early serum HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b plus ribavirin. METHODS: Male and female patients aged 18 to 65 years with chronic hepatitis C were eligible for the study. All patients received peginterferon alfa 2b 1.5 micrograms/kg once-weekly for 4 weeks and then peginterferon alfa 2b 0.5 microgram/kg once-weekly until the completion of the 48 week trial period, plus ribavirin orally with meals, adjusted to body weight. HCV RNA was determined at base-line, 48 hours, 4 and 12 weeks of therapy. RESULTS: Data were obtained from 20 patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin; 16 male, 4 female, with a mean age of 44.4 +/- 11.9 years, 16 patients (80%) were infected with HCV genotype 1, the remainder were infected with genotype 2. Mean baseline HCV RNA for the total group was 1,091,405 +/- 972,715 IU/mL. Mean reductions in viral load at 48 hours, 4 and 12 weeks for the 20 patients were 1.31 +/- 0.91 log, 1.99 +/- 1.27 log and 2.31 +/- 1.25 log, respectively. A > 2 log reduction in HCV RNA was noticed in 12/20 patients (60%) at 4 weeks (early viral responders), in 9 of them (45%) HCV RNA was undetectable. This response in HCV RNA persisted at 12 weeks of therapy. Early viral responders had a significant reduction in HCV RNA at 48 hours after the initial peginterferon alfa 2b injection (> 1 log reduction). Early viral response was observed in 8/16 patients with HCV genotype 1, and in all genotype 2 patients. CONCLUSION: Treatment with peginterferon alfa 2b and ribavirin produces significant changes in the early HCV viral dynamics supporting the concept that such changes may be pivotal in achieving a sustained viral response.

[Physiopathology of hepatitis C virus infection]. / Fisiopatología de la infección por el virus de la hepatitis C.

Pathogenesis of infection with HCV is not yet clear. Of course the most logical explanation is the direct viral damage, but that seems very improbable. Given that this virus isn't cytopathic, liver damage in chronic infection is probably related to an immune response of cellular type. Cytotoxic lymphocytes and helper lymphocytes recognize the HCV proteins and initiate the proinflammatory cytokine synthesis that lead to chronic inflammation which in turn may originate a malignant neoplasia.

Histoplasma panniculitis in a patient with systemic lupus erythematosus

Abstract: Histoplasmosis usually presents primarily as lung infection. Occasionally, mainly in immunocompromised hosts, it can spread and cause systemic manifestations. Skin lesions have been reported in 10 to 15 percent of cases of disseminated histoplasmosis, and panniculitis has been described as an unusual form of presentation in affected patients. We present the case of a patient with systemic lupus erythematosus who presented cellulitis due to disseminated histoplasmosis.

Prospective, randomized, open label trial of Efavirenz vs Lopinavir/Ritonavir in HIV+ treatment-naive subjects with CD4+<200 cell/mm3 in Mexico.

OBJECTIVE: To compare the efficacy of efavirenz (EFV) vs lopinavir/ritonavir (LPV/r) in combination with azidothymidine/lamivudine in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4 counts <200/mm. METHODS: Prospective, randomized, open label, multicenter trial in Mexico. HIV-infected subjects with CD4 <200/mm were randomized to receive open label EFV or LPV/r plus azidothymidine/lamivudine (fixed-dose combination) for 48 weeks. Randomization was stratified by baseline CD4 cell count (< or =100 or >100/mm). The primary endpoint was the percentage of patients with plasma HIV-1 RNA <50 copies/mL at 48 weeks by intention-to-treat analysis. RESULTS: A total of 189 patients (85% men) were randomized to receive EFV (95) or LPV/r (94). Median baseline CD4 were 64 and 52/mm, respectively (P = not significant). At week 48, by intention-to-treat analysis, 70% of EFV and 53% of LPV/r patients achieved HIV-1 RNA <50 copies/mL [estimated difference 17% (95% confidence interval 3.5 to 31), P = 0.013]. The proportion with HIV-1 RNA <400 copies/mL was 73% with EFV and 65% with LPV/r (P = 0.25). Virologic failure occurred in 7 patients on EFV and 17 on LPV/r. Mean CD4 count increases (cells/mm) were 234 for EFV and 239 for LPV/r. Mean change in total cholesterol and triglyceride levels were 50 and 48 mg/dL in EFV and 63 and 116 mg/dL in LPV/r (P = 0.24 and P < 0.01). CONCLUSIONS: In these very advanced HIV-infected ARV-naive subjects, EFV-based highly active antiretroviral therapy had superior virologic efficacy than LPV/r-based highly active antiretroviral therapy, with a more favorable lipid profile.

Mecanismos patogénicos de la infección por VIH

A pesar de los continuos avances que han ocurrido en el entendimiento de la forma en que el VIH produce daño destruyendo las células CD4+, no se han podido dilucidar los mecanismos específicos de virulencia y patogenicidad de este agente infeccioso y, por lo tanto, no se han podido diseñar las estrategias para su posible erradicación. Es muy importante profundizar en el entendimiento de la patogénesis de esta infección para poder combatirla y para este fin debemos de tratar de comprender fenómenos tan relevantes como la infección primaria, las variantes de la progresión a SIDA y en especial los determinantes de la relación virus-huésped.

Despite the recent advances in the understanding of the mechanisms of HIV induced T cell depletion, it has not been possible to elucidate the specific virulence factors and as a consequence to create effective strategies for its eradication. It is mandatory to understand deeply the pathogenetic mechanisms of the HIV infection in order to face possible ways to destroy it. In order to fulfill this goal, we have to understand better important events like primary infection, the differences in progression to AIDS and specially those determinants of the host-virus relationship.

Fisiopatología y tratamiento del síndrome de inmunodeficiencia adquirida / Physiopathology and treatment of acquired immunodeficiency syndrome

La última pandemia de este siglo, la del virus de inmunodeficiencia humana (VIH) y el síndrome de inmunodeficiencia adquirida (SIDA), sigue avanzando a pasos agigantados con 18,000 nuevos infectados por día alrededor del mundo. En los últimos cuatro años se han logrado descubrimientos significativos y se han introducido al mercado medicamentos que han cambiado drásticamente la progresión de la infección por VIH y la enfermedad (SIDA), disminuyendo en forma muy significativa la morbimortalidad asociada. El VIH se replica activamente durante todo el curso de la infección produciendo diariamente hasta 1010 viriones genéticamente distintos (cuasiespecies) lo que se relaciona con escape inmune, incremento en la patogenicidad y resistencia a medicamentos. La replicación viral persistente ocasiona por diferentes mecanismos destrucción de linfocitos T CD4+ e inmunodeficiencia. Existen en la actualidad 14 medicamentos antirretrovirales disponibles que combinados en triples terapias no sólo han logrado disminuir la mortalidad sino también la frecuencia de infecciones oportunistas y de hospitalizaciones. Desafortunadamente estos esquemas tienen aún muchas limitaciones, no son curativos y sólo suprimen el virus en forma sostenida en 50 por ciento de los pacientes tratados, además cuando se usan en forma inadecuada se asocian al desarrollo de resistencia. Por otra parte las indicaciones para inicio de tratamiento están cambiando continuamente, ahora con una tendencia más conservadora, y para las terapias de rescate sólo existen lineamientos generales que no han sido evaluados en ensayos clínicos. Los ensayos de resistencia tienen grandes limitaciones y sus aplicaciones son muy específicas. Todos estos factores hacen que el tratamiento antirretroviral sea cada vez más complicado por lo que se recomienda sea indicado y monitorizado por un experto.

Hepatitis viral C en pacientes con insuficiencia renal crónica terminal. III Cuantificación viral / Hepatitis C in patients with end stage renal disease. III viral load

Antecedentes. Previamente hemos demostrado que la hepatitis asociada a virus de hepatitis C (VHC) en pacientes con insuficiencia renal crónica terminal (IRCT) tiene una prevalencia en nuestro medio de 10.2 por ciento. Sin embargo, se desconocen los valores de carga viral en estos enfermos y su relación con diversas variables clínicas. En el presente trabajo determinamos cuantitativamente la presencia de RNA viral en suero de pacientes en diálisis e infección por VHC, con el objetivo de conocer este valor y correlacionarlo con los diferentes tipos de procedimientos sustitutivos de la función renal y genotipos virales.Métodos. Realizamos un estudio transversal, prolectivo y comparativo en pacientes con infección por VHC en hemodiálisis (HD), diálisis peritoneal continua ambulatoria (DPCA) y DPCA con historia de HD (DP/HD). La cuantificación viral se efectuó con base a la amplificación de un fragmento del RNA viral mediante reacción en cadena de la polimerasa con un estuche comercial (Amplicor HCV 2.0). Las variables analizadas fueron: edad, género, causa de la insuficiencia renal, tipo y tiempo en terapia sustitutiva, historial de transfusiones, historial clínico de hepatitis, pruebas de función hepática (albúmina sérica, bilirrubinas, aminotransferasas), nitrógeno ureico, creatinina sérica y biometría hemática.Resultados. El estudio se llevó a cabo en 24 pacientes con IRCT e infección por VHC, de los cuales, el 25 por ciento estaban en DPCA, 29 por ciento en DP/HD y 46 por ciento en HD. El promedio total de la carga viral fue de 1.41 ñ 3.01 copias x 106 por mL de suero. La carga viral expresada en número de copias × 106 fue significativamente menor en los pacientes con DPCA, en comparación con los pacientes que tienen o han estado en HD (0.20 ñ 0.12 vs. 2.04 ñ 0.88; p<0.05). No observamos ninguna relación entre la carga viral y los genotipos del VHC. Discusión. El promedio de la carga viral en nuestros pacientes es semejante a lo reportado, pero parece bajo cuando se compara con los títulos de carga viral en pacientes con infección por VHC no nefrópatas. La carga viral es menor cuando los enfermos infectados se encuentran en DPCA, probablemente por que la HD confiere cierto grado de inmunosupresión, lo que explicaría porqué la tasa de replicación viral es mayor.