Pharmacogenetic Associations Between Atazanavir/UGT1A1*28 and Efavirenz/rs3745274 (CYP2B6) Account for Specific Adverse Reactions in Chilean Patients Undergoing Antiretroviral Therapy.

Background: Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, and atazanavir (ATV), a protease inhibitor, are drugs widely used in antiretroviral therapy (ART) for people living with HIV. These drugs have shown high interindividual variability in adverse drug reactions (ADRs). UGT1A1*28 and CYP2B6 c.516G>T have been proposed to be related with higher toxicity by ATV and EFV, respectively. Objective: To study the association between genetic polymorphisms and ADRs related to EFV or ATV in patients living with HIV treated at a public hospital in Chile. Methods: Epidemiologic, case-control, retrospective, observational study in 67 adult patients under EFV or ATV treatment was conducted, in the San Juan de Dios Hospital. Data were obtained from patients' medical records. Genotype analyses were performed using rtPCR for rs887829 (indirect identification of UGT1A1*28 allele) and rs3745274 (CYP2B6 c.516G>T), with TaqMan® probes. The association analyses were performed with univariate logistic regression between genetic variants using three inheritance models (codominant, recessive, and dominant). Results: In ATV-treated patients, hyperbilirubinemia (total bilirubin >1.2 mg/dl) had the main incidence (61.11%), and moderate and severe hyperbilirubinemia (total bilirubin >1.9 mg/dl) were statistically associated with UGT1A1*28 in recessive and codominant inheritance models (OR = 16.33, p = 0.028 and OR = 10.82, p = 0.036, respectively). On the other hand, in EFV-treated patients adverse reactions associated with CNS toxicity reached 34.21%. In this respect, nightmares showed significant association with CYP2B6 c.516G>T, in codominant and recessive inheritance models (OR = 12.00, p = 0.031 and OR = 7.14, p = 0.042, respectively). Grouped CNS ADRs (nightmares, insomnia, anxiety, and suicide attempt) also showed a statistically significant association with CYP2B6 c.516G > T in the codominant and recessive models (OR = 30.00, p = 0.011 and OR = 14.99, p = 0.021, respectively). Conclusion: Our findings suggest that after treatment with ATV or EFV, UGT1A1*28 and CYP2B6 c.516G>T influence the appearance of moderate-to-severe hyperbilirubinemia and CNS toxicity, respectively. However, larger prospective studies will be necessary to validate these associations in our population. Without a doubt, improving adherence in patients living with HIV is a critical issue to the success of therapy. Hence, validating and applying international pharmacogenetic recommendations in Latin American countries would improve the precision of ART: a fundamental aspect to achieve the 95-95-95 treatment target proposed by UNAIDS.

[Nocardia cyriacigeorgica infection in AIDS patient]. / Infección por Nocardia cyriacigeorgica en paciente con infección por VIH en etapa SIDA.

Nocardiosis is a localized or systemic infection that mainly affects immunocompromised patients, with pulmonary localization being the most frequent site. The transmission comes mainly from the inhalation of spores or by direct inoculation into the skin and ocular mucosa. More than 90 species of nocardia are described, of which more than half are recognized as pathogens in humans. The best known species of medical importance are Nocardia farcinica, Nocardia abscessus, Nocardia nova y Nocardia brasiliensis. In Chile, there have been published cases of Nocardia asteroides and Nocardia farcinica infections. Nocardia cyriacigeorgica is considered an emerging species, there being no cases previously described in our country. We present a clinical case of pulmonary nocardiosis in an acquired immunodeficiency syndrome (AIDS) patient.

Infección por Nocardia cyriacigeorgica en paciente con infección por VIH en etapa SIDA / Nocardia cyriacigeorgica infection in AIDS patient

Resumen La nocardiosis es una infección localizada o sistémica que afecta principalmente a pacientes inmunocomprometidos, siendo la localización pulmonar el sitio más frecuente. La transmisión proviene principalmente de la inhalación de esporas o mediante la inoculación directa en la piel y mucosa ocular. Se han descrito más de 90 especies de Nocardia, de éstas más de la mitad son reconocidas como patógenos en humanos. Las especies de importancia médica más conocidas son Nocardia farcinica, Nocardia abscessus, Nocardia nova y Nocardia brasiliensis. En Chile hay casos publicados de infección por Nocardia asteroides y N. farcinica. Nocardia cyriacigeorgica se considera una especie emergente, no habiendo casos descritos previamente en nuestro país. Presentamos el caso clínico de una nocardiosis pulmonar en un paciente con síndrome de inmunodeficiencia adquirida (SIDA).

Abstract Nocardiosis is a localized or systemic infection that mainly affects immunocompromised patients, with pulmonary localization being the most frequent site. The transmission comes mainly from the inhalation of spores or by direct inoculation into the skin and ocular mucosa. More than 90 species of nocardia are described, of which more than half are recognized as pathogens in humans. The best known species of medical importance are Nocardia farcinica, Nocardia abscessus, Nocardia nova y Nocardia brasiliensis. In Chile, there have been published cases of Nocardia asteroides and Nocardia farcinica infections. Nocardia cyriacigeorgica is considered an emerging species, there being no cases previously described in our country. We present a clinical case of pulmonary nocardiosis in an acquired immunodeficiency syndrome (AIDS) patient.

[Campylobacter jejuni bacteremia in a patient with HIV infection in AIDS stage]. / Bacteriemia por Campylobacter jejuni en un paciente con infección por VIH en etapa SIDA.

Bacteremia is an atypical presentation of Campylobacter jejuni infection and it is more frequent in patients with advanced inmunodepression due to HIV or other sistemic diseases. Because of the highly active antiretroviral therapy, in the last decades the number of cases had declined. We report a case of a homeless woman with HIV in C3 stage who was diagnosed with the bacteremia during her hospitalization for pulmonary tuberculosis, and a brief review of C. jejuni bacteremia in HIV patients.

Bacteriemia por Campylobacter jejuni en un paciente con infección por VIH en etapa SIDA / Campylobacter jejuni bacteremia in a patient with HIV infection in AIDS stage

Resumen La bacteriemia es una presentación atípica de la infección por Campylobacter jejuni, y es más frecuente en pacientes con inmunodepresión avanzada debido al VIH u otras enfermedades sistémicas. Debido a la terapia anti-retroviral, en las últimas décadas el número de casos ha disminuido. Presentamos el caso de una mujer en situación de calle, con VIH en etapa C3, que cursó con una bacteriemia por C. jejuni durante su hospitalización por una tuberculosis pulmonar. Realizamos una breve revisión de bacteriemia por C. jejuni en pacientes con VIH.

Bacteremia is an atypical presentation of Campylobacter jejuni infection and it is more frequent in patients with advanced inmunodepression due to HIV or other sistemic diseases. Because of the highly active antiretroviral therapy, in the last decades the number of cases had declined. We report a case of a homeless woman with HIV in C3 stage who was diagnosed with the bacteremia during her hospitalization for pulmonary tuberculosis, and a brief review of C. jejuni bacteremia in HIV patients.

[Clinical utility of HIV viral load assessment in cerebral spinal fluid, a case report]. / Utilidad de la cuantificación de carga viral de VIH en líquido cefalorraquídeo, a propósito de un caso.

Detection of virus in cerebrospinal fluid (CSF) in HIV-infected patients with HIV viral load (VL) undetectable in plasma has been termed viral escape. These leaks may be asymptomatic from a neurological point of view, similar to plasma blips, or associated with neurological disease, with discordant VL between plasma and CSF, and may be evidence of a compartmentalization of the virus and the possibility of identifying quasispecies with mutations that confer resistance to ART. We present the case of a man with AIDS and disseminated tuberculosis who presented neurological symptomatology evidenced by headache and convulsive syndrome, who presented a discordance between plasma and CSF HIV VL; the genotypic test of the virus, obtained by lumbar puncture, identified new mutations that determined a change in ART with subsequent satisfactory evolution.

Utilidad de la cuantificación de carga viral de VIH en líquido cefalorraquídeo, a propósito de un caso / Clinical utility of HIV viral load assessment in cerebral spinal fluid, a case report

Resumen La detección de virus en el líquido cefalorraquídeo (LCR) en pacientes infectados por VIH con carga viral (CV) indetectable en el plasma se ha denominado escape viral. Estas fugas pueden ser asintomáticas o asociadas con enfermedad neurológica. La discordancia de la carga viral de VIH entre plasma y LCR evidenciaría la presencia de distintos compartimentos del virus, con la posibilidad de identificar quasiespecies con mutaciones específicas que confieran resistencia a la TARV. Presentamos el caso clínico de un paciente con infección por VIH en etapa SIDA y una tuberculosis diseminada que presentó un cuadro neurológico manifestado por cefalea y un síndrome convulsivo, en que se encontró una discordancia entre la CV para VIH en plasma y LCR. El estudio genotípico del virus obtenido del LCR identificó nuevas mutaciones que determinaron un cambio de la TARV, con evolución posterior satisfactoria.

Detection of virus in cerebrospinal fluid (CSF) in HIV-infected patients with HIV viral load (VL) undetectable in plasma has been termed viral escape. These leaks may be asymptomatic from a neurological point of view, similar to plasma blips, or associated with neurological disease, with discordant VL between plasma and CSF, and may be evidence of a compartmentalization of the virus and the possibility of identifying quasispecies with mutations that confer resistance to ART. We present the case of a man with AIDS and disseminated tuberculosis who presented neurological symptomatology evidenced by headache and convulsive syndrome, who presented a discordance between plasma and CSF HIV VL; the genotypic test of the virus, obtained by lumbar puncture, identified new mutations that determined a change in ART with subsequent satisfactory evolution.

[Daptomycin: pharmacological characteristics and its role in the treatment of gram positive infections]. / Daptomicina: características farmacológicas y aporte en el tratamiento de infecciones por cocáceas gram positivas.

Daptomycin recently made available in Chile, belongs to a new family of antimicrobials known as lypopeptides. Daptomycin has a unique mechanism of action and a potent bactericidal activity over susceptible agents. It is active against a number of clinically significant Gram positive cocci, including strains of Staphylococcus aureus and Enterococcus spp., both susceptible and resistant to classic antimicrobials. Daptomycin has been approved for clinical use in skin and soft tissue infections, and for S. aureus bacteremia in adult patients. Ongoing trials suggest that daptomycin is also useful in the treatment of other infections such as osteomyelitis, biofilm producing infections, and in immunocompromised patients, particularly onco-hematologic patients. The main adverse reaction associated with daptomycin use is myopathy, usually mild and reversible.

Daptomicina: características farmacológicas y aporte en el tratamiento de infecciones por cocáceas gram positivas / Daptomycin: pharmacological characteristics and its role in the treatment of gram positive infections

Daptomycin recently made available in Chile, belongs to a new family of antimicrobials known as lypopeptides. Daptomycin has a unique mechanism of action and a potent bactericidal activity over susceptible agents. It is active against a number of clinically significant Gram positive cocci, including strains of Staphylococcus aureus and Enterococcus spp., both susceptible and resistant to classic antimicrobials. Daptomycin has been approved for clinical use in skin and soft tissue infections, and for S. aureus bacteremia in adult patients. Ongoing trials suggest that daptomycin is also useful in the treatment of other infections such as osteomyelitis, biofilm producing infections, and in immunocompromised patients, particularly onco-hematologic patients. The main adverse reaction associated with daptomycin use is myopathy, usually mild and reversible.

Daptomicina es un anti-infeccioso de reciente introducción en Chile, miembro exclusivo de una nueva familia de antimicrobianos conocida como lipopéptidos cíclicos. Tiene un mecanismo de acción único que le confiere un potente efecto bactericida sobre los microorganismos susceptibles. Su especto antimicrobiano comprende cocáceas grampositivas de importancia clínica como Staphylococcus aureus y Enterococcus spp., incluyendo cepas resistentes a antimicrobianos habituales. Está aprobada para el uso clínico en infecciones de piel y tejidos blandos y bacteriemia complicada y no complicada por S. aureus, en adultos. Estudios en curso sugieren que será una alternativa útil en otras infecciones frecuentes como osteomielitis, infecciones asociadas a dispositivos ortopédicos, infecciones asociadas a biopelículas e infecciones en hospederos inmunosuprimidos, en particular en pacientes onco-hematológicos. El principal efecto adverso asociado al uso de daptomicina es la toxicidad muscular, observándose miopatía reversible, la mayoría de las veces asintomática, en aproximadamente 3% de los pacientes que utilizan el fármaco.