Evaluación de laboratorio de la función hepática en personas que inician terapia antirretroviral con Dolutegravir o Efavirenz: un estudio de cohorte en Belo Horizonte, Brasil

Autores/as

DOI:

https://doi.org/10.33448/rsd-v11i13.35082

Palabras clave:

Terapia Antirretroviral de Gran Actividad; Celulas hepáticas; Biomarcadores de respuesta a fármacos.

Resumen

Objetivo: verificar qué régimen de tratamiento antirretroviral fue más seguro para las personas que viven con el VIH, dolutegravir 50 mg + lamivudina 300 mg + tenofovir 300 mg o efavirenz 600 mg + lamivudina 300 mg + tenofovir 300 mg. Para ello se analizaron las siguientes pruebas de laboratorio de función hepática: bilirrubina total, directa e indirecta, aspartato amino transferasa, alanina amino transferasa, gamma glutamil transferasa y fosfatasa alcalina. Metodología: estudio de cohorte, con seguimiento de 234 personas viviendo con VIH e iniciando terapia antirretroviral en la ciudad de Belo Horizonte, Minas Gerais, Brasil, con datos recolectados entre agosto de 2015 y diciembre de 2018. Resultados: Valores medios para el los resultados de las pruebas de bilirrubina total e indirecta, aspartato amino transferasa, alanina amino transferasa y fosfatasa alcalina se redujeron después de 72 semanas para los dos regímenes terapéuticos. El valor medio de bilirrubina directa en personas que tomaban efavirenz aumentó a las 72 semanas y estuvo por encima del valor inicial en comparación con el valor inicial. Para gamma glutamil transferasa, la media de los resultados estaba por encima del valor de referencia en ambos grupos antes del tratamiento. Después de 72 semanas de tratamiento con dolutegravir, la media volvió al valor inicial y, en el caso de efavirenz, la media permaneció alta. Las pruebas de Bonett y Dunnett no tuvieron diferencia estadística, lo que indica que los dos regímenes terapéuticos son seguros. Conclusiones: los dos regímenes terapéuticos estudiados demostraron ser seguros y no provocaron un aumento en la varianza para los exámenes de laboratorio que fueron marcadores de la función hepática.

Citas

Agência Europeia De Medicamentos – EMA. (2012). Anexo I: resumo das características do medicamento – Efavirenz. https://ec.europa.eu/hea lth/documents/community- register/2012/20121025124790/anx_124790_pt.pdf.

Alghamdi, S., Alrbiaan, A., Alaraj, A., Alhuraiji, A., Alghamdi, M., & Alrajhi, A. (2016). Elevated alanine aminotransferase levels in HIV-infected persons without hepatitis B or C virus coinfection. Annals of Saudi Medicine, 36(4), 288–291. https://doi.org/10.5144/0256-4947.2016.288

Anyanwu, C. F., JohnBull, T. O., Usman, I. M., Aigbogun, E. O. J., Ochai, J., Qasem, A. H., Alkhayyat, S. S., Alexiou, A., & Batiha, G. E. S. (2021). Substance Use, Highly Active Antiretroviral Therapy, and Liver Enzymes: Evidence From a Cross-Sectional Study of HIV-Infected Adult Patients Without Comorbidities on HAART in the University of Port Harcourt Teaching Hospital. Frontier in Reproductive Health, 3(1), 1-12. https://doi.org/10.3389/frph.2021.664080

Brasil (2018). Protocolo Clínico e diretrizes terapêuticas para manejo da infecção pelo HIV em adultos. Ministério da Saúde.

Brasil (2018a). Protocolo Clínico e Diretrizes Terapêuticas para Manejo da Infecção pelo HIV em Crianças e Adolescentes. Ministério da Saúde.

Cai, J., Osikowicz, M., & Sebastiani, G. (2019). Clinical significance of liver transaminases in HIV-infected patients. AIDS, 33(8), 1267–1282. https://doi.org/10.1097/QAD.0000000000002233

Chen, S., St Jean, P., Borland, J., Song, I., Yeo, A. J., Piscitelli, S., & Rubio, J. P. (2014). Evaluation of the effect of UGT1A1 polymorphisms on dolutegravir pharmacokinetics. Pharmacogenomics, 15(1), 9-16. https://doi.org/10.2217/pgs.13.190

Cysne, A. C., Torga, E. D. G. C., Luzia, E. L., Lemos, L. M. C., Souza, L. M. S., Rocha, M. A. P., Siqueira, S. B., & Resende, S. E (2016). Manual de Exames Laboratoriais da rede SUS-BH. 1 ed. Prefeitura Municipal de Belo Horizonte.

Dusingize, J. C., Hoover, D. R., Shi, Q., Mutimura, E., Rudakemwa, E., Ndacyayisenga, V., Gakindi, L., Mulvihill, M., Sinayobye, J. D., Musabeyezu, E., & Anastos, K. (2015). Association of Abnormal Liver Function Parameters with HIV Serostatus and CD4 Count in Antiretroviral-Naive Rwandan Women. AIDS Research And Human Retroviruses, 31(7), 723–730. https://doi.org/10.1089/AID.2014.0170

Ejilemele, A. A., Nwauche, C. A., & Ejele, O. A. (2007). Pattern of abnormal liver enzymes in HIV patients presenting at a Nigerian Tertiary Hospital. The Nigerian Postgraduate Medical Journal, 14(4), 306–309. https://pubmed.ncbi.nlm.nih.gov/18163139/

Gebremicael, G., Tola, H. H., Gebreegziaxier, A., & Kassa, D. (2021). Incidence of Hepatotoxicity and Factors Associated During Highly Active Antiretroviral Therapy in People Living with HIV in Ethiopia: A Prospective Cohort Study. HIV/AIDS, 13(1), 329–336. https://doi.org/10.2147/HIV.S283076

Gil, A. C. M., Lorenzetti, R., Mendes, G. B., Morcillo, A. M., Toro, A. A. D. C., Silva, M. T. N. D., & Vilela, M. M. D. S. (2007). Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy. Sao Paulo Medical Journal, 125(1), 205-209.

Kalyesubula, R., Kagimu, M., Opio, K. C., Kiguba, R., Semitala, C. F., Schlech, W. F., & Katabira, E. T. (2011). Hepatotoxicity from first line antiretroviral therapy: an experience from a resource limited setting. African Health Sciences, 11(1), 16–23. https://pubmed.ncbi.nlm.nih.gov/21572852/

Kimm, H., Kim, S., & Jee, S. H. (2010). The independent effects of cigarette smoking, alcohol consumption, and serum aspartate aminotransferase on the alanine aminotransferase ratio in korean men for the risk for esophageal cancer. Yonsei Medical Journal, 51(3), 310–317. https://doi.org/10.3349/ymj.2010.51.3.310

Kim, W. R., Flamm, S. L., Di Bisceglie, A. M., Bodenheimer, H. C., & Public Policy Committee of the American Association for the Study of Liver Disease (2008). Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology, 47(4), 1363–1370. https://doi.org/10.1002/hep.22109

Kontorinis, N., & Dieterich, D. (2003). Hepatotoxicity of antiretroviral therapy. AIDS Reviews, 5(1), 36–43. https://pubmed.ncbi.nlm.nih.gov/12875106/

Lucien, K., Clement, A., Fon, N., Weledji, P., & Ndikvu, C. (2010). The effects of antiretroviral treatment on liver function enzymes among HIV-infected out patients attending the central hospital of Yaounde, Cameroon. African Journal of Clinical and Experimental Microbiology, 11(3),174-178. https://doi.org/10.4314/ajcem.v11i3.57777

Martins, A. C. M., Oliveira, E. B., Roman, R (2020). TeleCondutas: HIV: acompanhamento e tratamento de pessoas vivendo com HIV/AIDS na Atenção Primária à Saúde: versão digital 2020. Universidade Federal do Rio Grande do Sul. https://www.ufrgs.br/telessauders/teleconsultoria/0800-644-6543/#telecondutas-0800.

Mata-Marín, J. A., Gaytán-Martínez, J., Grados-Chavarría, B. H., Fuentes-Allen, J. L., Arroyo-Anduiza, C. I., & Alfaro-Mejía, A. (2009). Correlation between HIV viral load and aminotransferases as liver damage markers in HIV infected naive patients: a concordance cross-sectional study. Virology Journal, 6(1),1-4. https://doi.org/10.1186/1743-422X-6-181

Mendes, J. C., Bonolo, P. F., Ceccato, M., Costa, J. O., Reis, A., Dos Santos, H., & Silveira, M. R. (2018). Adverse reactions associated with first-line regimens in patient initiating antiretroviral therapy. European journal of clinical pharmacology, 74(8), 1077–1088. https://doi.org/10.1007/s00228-018-2472-y

Minas Gerais (2018). Boletim epidemiológico mineiro: análise epidemiológica de HIV/aids. Panorama do ano de 2017. Secretaria Estadual de Saúde.

Mulu, W., Gidey, B., Chernet, A., Alem, G., & Abera, B. (2013). Hepatotoxicity and associated risk factors in HIV-infected patients receiving antiretroviral therapy at Felege Hiwot Referral Hospital, Bahirdar, Ethiopia. Ethiopian Journal of Health Sciences, 23(3), 217–226. https://doi.org/10.4314/ejhs.v23i3.4

Oikonomou, K. G., Tsai, E., Sarpel, D., & Dieterich, D. T. (2019). Liver Disease in Human Immunodeficiency Virus Infection. Clinics in Liver Disease, 23(2), 309–329. https://doi.org/10.1016/j.cld.2018.12.011

Otto, A. O., Rivera, C. G., Zeuli, J. D., & Temesgen, Z. (2021). Hepatotoxicity of Contemporary Antiretroviral Drugs: A Review and Evaluation of Published Clinical Data. Cells, 10(5), 1-21. https://doi.org/10.3390/cells10051263

Park, E. Y., Lim, M. K., Oh, J. K., Cho, H., Bae, M. J., Yun, E. H., Kim, D. I., & Shin, H. R. (2013). Independent and supra-additive effects of alcohol consumption, cigarette smoking, and metabolic syndrome on the elevation of serum liver enzyme levels. PloS One, 8(5), e63439. https://doi.org/10.1371/journal.pone.0063439

Segamwenge, I. L., & Bernard, M. K. (2018). Acute Liver Failure among Patients on Efavirenz-Based Antiretroviral Therapy. Case Reports in Hepatology, 2018(1), 1-5. https://doi.org/10.1155/2018/1270716

Silva, K. M. M.; Neves, R. A.; & Costa, S. H. N. (2021). Prevalência de alterações da gama-glutamil transferase e hematológicas em indivíduos que relataram uso de álcool. Revista Brasileira Militar de Ciências. 7(17), 23-30. https://rbmc.emnuvens.com.br/rbmc/article/view/86/53

Shiferaw, M. B., Tulu, K. T., Zegeye, A. M., & Wubante, A. A. (2016). Liver Enzymes Abnormalities among Highly Active Antiretroviral Therapy Experienced and HAART Naïve HIV-1 Infected Patients at Debre Tabor Hospital, North West Ethiopia: A Comparative Cross-Sectional Study. AIDS Research and Treatment, 2016, 1985452. https://doi.org/10.1155/2016/1985452

Teixeira, L. S., Ceccato, M. G. B., Carvalho, W. S., Costa, J. O., Bonolo, F. P., Mendes, J. C., & Silveira, M. R. (2020). Prevalência e fatores associados ao tabagismo em pessoas vivendo com HIV em tratamento. Revista de Saúde Pública, 54(1), 01-13. https://doi.org/10.11606/s1518-8787.2020054001828

Telli, E. M. R. P.; Frigeri, M.; & Mello, S. R. (2016). Avaliação da atividade de enzimas hepáticas em dependentes, ex-dependentes e não usuários do etanol. Revista Brasileira de Análises Clínicas. Santa Catarina, 48(3), 245-52.

Tesfa, E., Siefu, D., Belayneh, Y., & Mekonnen, Z. (2019). Liver enzyme elevation in patients taking HAART compared with treatment naïve controls at Debre Berhan Referral Hospital: a comparative cross-sectional study, Northeast Ethiopia. BMC Research Notes, 12(1), 714. https://doi.org/10.1186/s13104-019-4748-4

Wannamethee, S. G., & Shaper, A. G. (2010). Cigarette smoking and serum liver enzymes: the role of alcohol and inflammation. Annals of clinical biochemistry, 47(4), 321–326. https://doi.org/10.1258/acb.2010.009303

Woldu, M. A., Getaneh, H. D., Lenjisa, J. L., Tegegn, G. T., Umeta, G. T., & Ayano, H. D. (2014). The Risk of Hepatotoxicity Associated with HAART/Anti-Tb Co-Treatment: A Case Control Study in a Central Ethiopian Referral Hospital. Family Medicine and Medical Science Research, 3(3), 1-6. http://dx.doi.org/10.4172/2327-4972.1000129

Wood, S., Byrne, M., Deiss, R., Okulicz, J., O’Bryan, T., Schofield, C., & Ganesan, A. (2017). The incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV-monoinfected persons. In Open Forum Infectious Diseases, 4(1), 220-221. https://doi.org/10.1093/ofid/ofx163.450

Wood, S., Won, S. H., Hsieh, H. C., Lalani, T., Kronmann, K., Maves, R. C., Utz, G., Schofield, C., Colombo, R. E., Okulicz, J. F., Blaylock, J., Agan, B. K., & Ganesan, A. (2021). Risk Factors Associated With Chronic Liver Enzyme Elevation in Persons With HIV Without Hepatitis B or C Coinfection in the Combination Antiretroviral Therapy Era. Open Forum Infectious Diseases, 8(3), ofab076. https://doi.org/10.1093/ofid/ofab076

Wu, P. Y., Cheng, C. Y., Liu, C. E., Lee, Y. C., Yang, C. J., Tsai, M. S., Cheng, S. H., Lin, S. P., Lin, D. Y., Wang, N. C., Lee, Y. C., Sun, H. Y., Tang, H. J., & Hung, C. C. (2017). Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan. PloS One, 12(2), e0171596. https://doi.org/10.1371/journal.pone.0171596

Publicado

28/09/2022

Cómo citar

CESAR, J. J. .; SILVEIRA, M. R.; MAIA, P. R. .; SOUZA, C. R. de .; PENIDO, H. P. de A. .; FERNANDES, A. C. da S. .; CECCATO, M. das G. B. Evaluación de laboratorio de la función hepática en personas que inician terapia antirretroviral con Dolutegravir o Efavirenz: un estudio de cohorte en Belo Horizonte, Brasil . Research, Society and Development, [S. l.], v. 11, n. 13, p. e74111335082, 2022. DOI: 10.33448/rsd-v11i13.35082. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/35082. Acesso em: 5 jul. 2024.

Número

Sección

Ciencias de la salud