Impact of fluvoxamine on outpatient treatment of COVID-19 in Honduras in a prospective observational real-world study.

Background: The COVID-19 pandemic has impacted millions of lives globally. While COVID-19 did not discriminate against developed or developing nations, it has been a significant challenge for third world countries like Honduras to have widespread availability of advanced therapies. The concept of early treatment was almost unheard of when early outpatient treatments utilizing repurposed drugs in Latin American countries began showing promising results. One such drug is fluvoxamine, which has shown tremendous potential in two major studies. As a direct result, fluvoxamine was added to the standard of care in a major medical center outpatient COVID-19 clinic. Methods: This is a prospective observational study performed at the Hospital Centro Médico Sampedrano (CEMESA) in San Pedro Sula, Cortes, Honduras in the COVID-19 outpatient clinic. All patients were at least 15 years of age who had presented with mild or moderate signs and symptoms of COVID-19, and who also had a documented positive SARS-CoV-2 antigen or Reverse Transcription Polymerase Chain Reaction (RT-PCR) were included in the study. These patients then were all prescribed fluvoxamine. The cohort of patients who decided to take fluvoxamine were compared for primary endpoints of mortality and hospitalization risk to the cohort who did not take fluvoxamine. Patients were then monitored for 30 days with the first follow up at 7 days and the second follow up at 10-14 days of symptom onset. Categorical variables were compared by Pearson Chi-square test. The Relative risk was calculated using regression models. Continuous variables were compared by t-test and Wilcoxon rank-sum tests. Results: Out of total 657 COVID-19 cases, 594 patients took fluvoxamine and 63 did not take fluvoxamine. A total of five patients (0.76 percent) died, with only one death occurring in the fluvoxamine group. Patients who received fluvoxamine had a significantly lower relative risk of mortality (RR 0.06, p 0.011, 95% CI 0.007-0.516). There was a lower relative risk of hospitalization in the patients who in the fluvoxamine group. (-10 vs. 30 hospitalizations, RR 0.49, p = 0.035, 95% CI 0.26-0.95). There was 73 percent reduction in relative risk of requiring oxygen in the fluvoxamine group (RR 0.27, p < 0.001, 95% CI 0.14-0.54 Mean lymphocytes count on the first follow-up visit was significantly higher in the fluvoxamine group (1.72 vs. 1.38, Δ 0.33, p 0.007, CI 0.09-0.58). Conclusion: The results of our study suggest that fluvoxamine lowers the relative risk of death, hospitalization, and oxygen requirement in COVID 19 patients.

COVID-19 Associated Rhino-Orbital Mucormycosis Complicated by Gangrenous and Bone Necrosis-A Case Report from Honduras.

BACKGROUND: Mucormycosis is a life-threatening invasive fungal infection most commonly observed in immunocompromised patients. Throughout the COVID-19 pandemic, a growing number of Mucorales associated infections, now termed COVID-19 associated mucormycosis (CAM), have been reported. Despite an increase in fatality reports, no cases of rhino-orbital CAM complicated with gangrenous bone necrosis have been described in the literature to date. CASE: A 56-year-old male with a recent COVID-19 diagnosis developed rhino-orbital mucormycosis after 22 days of treatment with dexamethasone. Cultures and histopathological assessment of tissue biopsy confirmed the diagnosis. The patient survived after treatment with amphotericin B. CONCLUSIONS: Mucormycosis is an invasive fungal infection affecting mostly immunocompromised patients. Along with the COVID-19 pandemic, the inappropriate use of steroids, in addition to concurrent risk factors, such as diabetes, has led to an increase in the occurrence of these devastating mycoses, leading to the development of severe presentations and complications, as observed in many cases. Early diagnosis and prompt treatment are crucial in order to avoid dissemination and fatal outcomes.

Using Prenatal Blood Samples to Evaluate COVID-19 Rapid Serologic Tests Specificity.

INTRODUCTION: Background cross-reactivity with other coronaviruses may reduce the specificity of COVID-19 rapid serologic tests. The vast majority of women attend prenatal care, which is a unique source of population-based blood samples appropriate for validation studies. We used stored 2018 serum samples from an existing pregnancy cohort study to evaluate the specificity of COVID-19 serologic rapid diagnostic tests. METHODS: We randomly selected 120 stored serum samples from pregnant women enrolled in a cohort in 2018 in Tegucigalpa, Honduras, at least 1 year before the COVID-19 pandemic. We used stored serum to evaluate four lateral flow rapid diagnostic tests, following manufacturers' instructions. Pictures were taken for all tests and read by two blinded trained evaluators. RESULTS: We evaluated 120, 80, 90, and 90 samples, respectively. Specificity for both IgM and IgG was 100% for the first two tests (95% confidence intervals [CI] 97.0-100 and 95.5-100, respectively). The third test had a specificity of 98.9% (95% CI 94.0-100) for IgM and 94.4% (95% CI 87.5-98.2) for IgG. The fourth test had a specificity of 88.9% (95% CI 80.5-94.5) for IgM and 100% (95% CI 96.0-100) for IgG. DISCUSSION: COVID-19 serologic rapid tests are of variable specificity. Blood specimens from sentinel prenatal clinics provide an opportunity to validate serologic tests with population-based samples.

Novel HLA class I associations with HIV-1 control in a unique genetically admixed population.

Associations between HLA class I alleles and HIV progression in populations exhibiting Amerindian and Caucasian genetic admixture remain understudied. Using univariable and multivariable analyses we evaluated HLA associations with five HIV clinical parameters in 3,213 HIV clade B-infected, ART-naïve individuals from Mexico and Central America (MEX/CAM cohort). A Canadian cohort (HOMER, n = 1622) was used for comparison. As expected, HLA allele frequencies in MEX/CAM and HOMER differed markedly. In MEX/CAM, 13 HLA-A, 24 HLA-B, and 14 HLA-C alleles were significantly associated with at least one clinical parameter. These included previously described protective (e.g. B*27:05, B*57:01/02/03 and B*58:01) and risk (e.g. B*35:02) alleles, as well as novel ones (e.g. A*03:01, B*15:39 and B*39:02 identified as protective, and A*68:03/05, B*15:30, B*35:12/14, B*39:01/06, B*39:05~C*07:02, and B*40:01~C*03:04 identified as risk). Interestingly, both protective (e.g. B*39:02) and risk (e.g. B*39:01/05/06) subtypes were identified within the common and genetically diverse HLA-B*39 allele group, characteristic to Amerindian populations. While HLA-HIV associations identified in MEX and CAM separately were similar overall (Spearman's rho = 0.33, p = 0.03), region-specific associations were also noted. The identification of both canonical and novel HLA/HIV associations provides a first step towards improved understanding of HIV immune control among unique and understudied Mestizo populations.

Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection.

OBJECTIVE: Long-acting rilpivirine is a candidate for preexposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing human leukocyte antigen (HLA)-B18 where reverse transcriptase-E138X arises as an immune escape mutation. We investigate the global prevalence, B18-linkage and replicative cost of reverse transcriptase-E138X and its regional implications for rilpivirine PrEP. METHODS: We analyzed linked reverse transcriptase-E138X/HLA data from 7772 antiretroviral-naive patients from 16 cohorts spanning five continents and five HIV-1 subtypes, alongside unlinked global reverse transcriptase-E138X and HLA frequencies from public databases. E138X-containing HIV-1 variants were assessed for in-vitro replication as a surrogate of mutation stability following transmission. RESULTS: Reverse transcriptase-E138X variants, where the most common were rilpivirine resistance-associated mutations E138A/G/K, were significantly enriched in HLA-B18-positive individuals globally (P = 3.5 × 10) and in all HIV-1 subtypes except A. Reverse transcriptase-E138X and B18 frequencies correlated positively in 16 cohorts with linked HIV/HLA genotypes (Spearman's R = 0.75; P = 7.6 × 10) and in unlinked HIV/HLA data from 43 countries (Spearman's R = 0.34, P = 0.02). Notably, reverse transcriptase-E138X frequencies approached (or exceeded) 10% in key epidemic regions (e.g. sub-Saharan Africa, Southeastern Europe) where B18 is more common. This, along with the observation that reverse transcriptase-E138X variants do not confer in-vitro replicative costs, supports their persistence, and ongoing accumulation in circulation over time. CONCLUSIONS: Results illustrate the potential for a natural immune-driven HIV-1 polymorphism to compromise antiretroviral-based prevention, particularly in key epidemic regions. Regional reverse transcriptase-E138X surveillance should be undertaken before use of rilpivirine PrEP.

Identification of major routes of HIV transmission throughout Mesoamerica.

BACKGROUND: Migration and travel are major drivers of the spread of infectious diseases. Geographic proximity and a common language facilitate travel and migration in Mesoamerica, which in turn could affect the spread of HIV in the region. METHODS: 6092 HIV-1 subtype B partial pol sequences sampled from unique antiretroviral treatment-naïve individuals from Mexico (40.7%), Guatemala (24.4%), Honduras (19%), Panama (8.2%), Nicaragua (5.5%), Belize (1.4%), and El Salvador (0.7%) between 2011 and 2016 were included. Phylogenetic and genetic network analyses were performed to infer putative relationships between HIV sequences. The demographic and geographic associations with clustering were analyzed and viral migration patterns were inferred using the Slatkin-Maddison approach on 100 iterations of random subsets of equal number of sequences per location. RESULTS: A total of 1685/6088 (27.7%) of sequences linked with at least one other sequence, forming 603 putative transmission clusters (range: 2-89 individuals). Clustering individuals were significantly more likely to be younger (median age 29 vs 33years, p<0.01) and men-who-have-sex-with-men (40.4% vs 30.3%, p<0.01). Of the 603 clusters, 30 (5%) included sequences from multiple countries with commonly observed linkages between Mexican and Honduran sequences. Eight of the 603 clusters included >10 individuals, including two comprised exclusively of Guatemalans (52 and 89 individuals). Phylogenetic and migration analyses suggested that the Central and Southern regions of Mexico along with Belize were major sources of HIV throughout the region (p<0.01) with genetic flow southward from Mexico to the other nations of Mesoamerica. We also found evidence of significant viral migration within Mexico. CONCLUSION: International clusters were infrequent, suggesting moderate migration between HIV epidemics of the different Mesoamerican countries. Nevertheless, we observed important sources of transnational HIV spread in the region, including Southern and Central Mexico and Belize.

HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy.

INTRODUCTION: We assessed HIV drug resistance (DR) in individuals failing ART (acquired DR, ADR) and in ART-naïve individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART. METHODS: 365 HIV-infected, ART-naïve, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIVDR mutation list and the Stanford algorithm. Recently infected (RI) individuals were identified using a multi-assay algorithm. RESULTS: PDR to any ARV drug was 11.5% (95% CI 8.4-15.2%). NNRTI PDR prevalence (8.2%) was higher than NRTI (2.2%) and PI (1.9%, p<0.0001). No significant trends in time were observed when comparing 2013 and 2014, when using a moving average approach along the study period or when comparing individuals with >500 vs. <350 CD4+ T cells/µL. PDR in recently infected individuals was 13.6%, showing no significant difference with PDR in individuals with longstanding infection (10.7%). The most prevalent PDR mutations were M46IL (1.4%), T215 revertants (0.5%), and K103NS (5.5%). The overall ADR prevalence in individuals with <48 months on ART was 87.8% and for the ≥48 months on ART group 81.3%. ADR to three drug families increased in individuals with longer time on ART (p = 0.0343). M184V and K103N were the most frequent ADR mutations. PDR mutation frequency correlated with ADR mutation frequency for PI and NNRTI (p<0.01), but not for NRTI. Clusters of viruses were observed suggesting transmission of HIVDR both from ART-experienced to ART-naïve individuals and between ART-naïve individuals. CONCLUSIONS: The global PDR prevalence in Honduras remains at the intermediate level, after 10 years of widespread availability of ART. Evidence of ADR influencing the presence of PDR was observed by phylogenetic analyses and ADR/PDR mutation frequency correlations.

Complicaciones temibles en un paciente con VIH/SIDA criptococosis, tuberculosis miliar, meningoencefalitis / Fearsome Complications in a Patient with HIV/AIDS: Cryptococcosis, Miliary Tuberculosis, Meningoencephalitis

Los criptococos son un grupo de hongos que se encuentran en el suelo donde hay aves, fundamentalmente palomas. De las diversas especies de criptococo, solamente resulta patógeno para el hombre Cryptoccocus neoformans. La manifestación más frecuente de esta infección es la meningoencefalitis, que afecta principalmente a pacientes inmuno comprometidos. La tuberculosis miliar representa una entidad poco frecuente dentro de las formas de presentación extrapulmonar de la tuberculosis, en pacientes inmunocompetentes. Sin embargo, en los pacientes infectados por el virus de la inmunodeficiencia humana, esta cifra oscila alrededor de 10%. Se presenta un reporte de caso, donde el paciente cursó con esta forma de Tuberculosis. Caso Clínico: Paciente masculino de 53 años, con cuadro de evacuaciones diarreicas crónicas intermitentes, fiebre diaria, vómitos postprandiales 4 a 5 veces al día, de 3 meses de evolución, cefalea intensa de 10 días, concomitantemente presentó una convulsión tónico clónica hace una semana. Además tos crónica con expectoración blanquecina y hemoptisis. Al examen físico se observó microadenopatías cervicales bilaterales, hipoventilación pulmonar bilateral, desviación de la lengua y comisura labial hacia lado derecho, disminución de fuerza en ambos miembros inferiores y superior derecho. Se realiza prueba para la detección de VIH, la cual resulta positiva, con conteo de 10 células CD4, punción lumbar en donde se obtiene líquido cefalorraquídeo ligeramente turbio, tinta china y antígena para criptococo positivo. Paciente es diagnosticado con VIH y SIDA, criptococosis del sistema nervioso central, tuberculosis miliar por rayos X, y meningoencefalitis. Se inicia cobertura antibiótica y antifímica a la cual el paciente respondió favorablemente...

Tuberculosis y SIDA: una co-infección eficiente / Tuberculosis and HIV an efficient co-infection

La co-infección tuberculosis/VIH es una de los problemas de salud más importantes del ser humano en particular en los países pobres y entre los jóvenes. El VIH incrementa el riesgo de enfermar de TB y la TB acelera el curso del VIH/Sida. En nuestro país la coinfección Tb/VIH es bastante común, siendo la TB la enfermedad más frecuente entre los pacientes VIH y el VIH el factor de riesgo más importante para desarrollar TB. Hay que distinguir entre infección y enfermedad en ambas patologías porque el abordaje diagnóstico y terapéutico es diferente. Consideramos importante que los médicos y personal de salud reconozcan las similitudes y diferencias en el diagnostico, abordaje terapéutico y prevención que caracterizan esta coinfección de la tuberculosis sin VIH, así como exponer las estrategias y políticas para prevenir y enfrentarla co-infección por lo que se efectuó por lo tanto una revisión de la literatura relacionada con el tema actualizada hasta el año 2009...

Tuberculosis y SIDA: una co-infección eficiente / Tuberculosis and HIV an efficient co-infection

La co-infección tuberculosis/VIH es una de los problemas de salud más importantes del ser humano en particular en los países pobres y entre los jóvenes. El VIH incrementa el riesgo de enfermar de TB y la TB acelera el curso del VIH/Sida. En nuestro país la coinfección Tb/VIH es bastante común, siendo la TB la enfermedad más frecuente entre los pacientes VIH y el VIH el factor de riesgo más importante para desarrollar TB. Hay que distinguir entre infección y enfermedad en ambas patologías porque el abordaje diagnóstico y terapéutico es diferente. Consideramos importante que los médicos y personal de salud reconozcan las similitudes y diferencias en el diagnostico, abordaje terapéutico y prevención que caracterizan esta coinfección de la tuberculosis sin VIH, así como exponer las estrategias y políticas para prevenir y enfrentarla co-infección por lo que se efectuó por lo tanto una revisión de la literatura relacionada con el tema actualizada hasta el año 2009...(AU)

Prevalence of resistance mutations in HIV-1-Infected Hondurans at the beginning of the National Antiretroviral Therapy Program.

The Honduran Ministry of Health (MOH) HIV antiretroviral treatment program began widespread treatment in 2003. We investigated the prevalence of antiretroviral genotypic resistance in specimens collected and archived from HIV-1-infected antiretroviral-naive patients presenting to initiate treatment between 1 July, 2002 and 30 June, 2003 in San Pedro Sula and Tegucigalpa, Honduras. Of 416 specimens collected, 336 (80.8%) were successfully genotyped. All genotypes were HIV-1, group M and 99.1% were subtype B. The prevalence of nucleoside reverse transcriptase inhibitor mutations was 7.7% with M184V and T215F/Y present in 6.0% and 3.0%, respectively. The prevalence of nonnucleoside reverse transcriptase inhibitor mutations was 7.1%. K103N mutations were present in 3.0% of study specimens. The prevalence of major protease inhibitor mutations was 2.7%. Overall, 9.2% of the specimens harbored clinically significant mutations that predict at least intermediate resistance to the Honduran first-line antiretroviral medications. These mutations were more common in San Pedro Sula (14.0%) than in Tegucigalpa (6.5%, p = 0.02). A significant number of patients presenting to initiate antiretroviral therapy in Honduran MOH clinics harbored HIV-1 isolates resistant to the MOH's first-line regimen and resistance varied by region. Further studies to assess the impact of the Honduran antiretroviral program on genotypic resistance are warranted.

Estudio clínico retrospectivo de tuberculosis y SIDA en el Instituto Nacional del Tórax, Tegucigalpa, Honduras / Tuberculosis and AIDS in Instituto Nacional del Torax, Tegucigalpa, Honduras

El presente es un estudio retrospectivo de 5 años y medio, que analiza 133 casos de pacientes con tuberculosis y SIDA. atendidos en elInstituto Nacional del Tórax; con el objeto de determinar las cracterísticas clínicas y evolución de los pacientes con la doble infección. La edad media de los pacientes fue 34 años, co predominio del sexo masculino sobre el femenino de 2.6:1. La evolución del cuadro clínico fue menor de 4 meses en el 69.5 por ciento de los pacintes y el diagnóstico de tuberculosis y SIDA fue simultaneo en 69.9 por ciento de los casos. La PPD fue positiva en 38.3 por ciento de las personas, y la basiloscopía en 59.1 por ciento .La tuberculosis fue pulmonar en 64.4 por ciento Y desiminada en 28.6 por ciento de los pacientes, afectando ganglios (24.1 por ciento ), SNC (11.3 por ciento ), peritoneo (3.8 por ciento ), huesos (2.3 por ciento ) y piel (0.8 por ciento ). La radiografía de tórax mostró lesiones "severas" en 58.1 por ciento y formas "atipicas" en 78.8 por ciento de los pacientes. La media del leucograma fue de 5000 leucocitos. El seguimiento de los pacientes fue de 6 meses en 11.3 por ciento y de un año en 7.5 por ciento . Al momento del alta los pacientes se encontraban mejorados el 48.9 por ciento , sin mejoría y muertos 46.6 por ciento . Se concluye que el comportamiento clínico no difiere del reportado en la literatura internacional, que el número de casos aumenta cada año, y que exista la necesidad de mejorar los métodos auxiliares de diasgnóstico, y el seguimiento de los pacientes.