| Author | Ngongondo, McNeil | |
| Author | Miyahara, Sachiko | |
| Author | Hughes, Michael D. | |
| Author | Sun, Xin | |
| Author | Bisson, Gregory P. | |
| Author | Gupta, Amita | |
| Author | Kumwenda, Johnstone | |
| Author | Lavenberg, Jeffrey A. | |
| Author | Torres, Thiago Silva | |
| Author | Nyirenda, Mulinda | |
| Author | Kidonge, Katende Kenneth | |
| Author | Hosseinpour, Mina C. | |
| Access date | 2024-09-24T14:45:11Z | |
| Available date | 2024-09-24T14:45:11Z | |
| Document date | 2018 | |
| Citation | NGONGONDO, McNeil et al. Hepatotoxicity during Isoniazid Preventive Therapy and Antiretroviral Therapy in People Living with HIV with Severe Immunosuppression: a Secondary Analysis of a Multi-country Open-label Randomized Controlled Clinical Trial. Journal of Acquired Immune Deficiency Syndromes, v. 78, n. 1, p. 1-19, May 2018. | |
| ISSN | 1525-4135 | |
| URI | https://www.arca.fiocruz.br/handle/icict/66066 | |
| Description | AIDS Clinical Trials Group A5274 (REMEMBER) Study Team. | en_US |
| Language | eng | en_US |
| Publisher | Lippincott Williams & Wilkins | |
| Later version | https://www.arca.fiocruz.br/handle/icict/30363 | |
| Rights | open access | |
| Subject in Portuguese | Isoniazida | pt_BR |
| Subject in Portuguese | ART | pt_BR |
| Subject in Portuguese | Hepatotoxicidade | pt_BR |
| Subject in Portuguese | HIV | pt_BR |
| Subject in Portuguese | Imunossupressão | pt_BR |
| Title | Hepatotoxicity during Isoniazid Preventive Therapy and Antiretroviral Therapy in People Living with HIV with Severe Immunosuppression: a Secondary Analysis of a Multi-country Open-label Randomized Controlled Clinical Trial | en_US |
| Type | Preprint | |
| DOI | 10.1097/QAI.0000000000001641 | |
| Abstract | Background: Hepatotoxicity associated with isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) has not been well studied in severely immunosuppressed people with HIV. Our objective was to determine risk factors for hepatotoxicity in severely immunosuppressed individuals taking IPT and ART. Setting: Multicenter study in resource-limited settings with high burden of tuberculosis. Methods: We conducted a secondary analysis of data from 1 randomized arm of the REMEMBER trial. The analysis includes participants with pre-ART CD4 cell counts of <50 cells/μL receiving IPT and ART for 24 weeks. Hepatotoxicity was defined as elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 × upper limit of normal or symptomatic hepatitis during IPT and ART. Logistic regression was used to identify baseline risk factors for hepatotoxicity. Time to occurrence of hepatotoxicity was estimated by the Kaplan-Meier method. Results: Among 426 participants (53% male, median age 35 years, median CD4 count 19 cells/µL), 31 developed hepatotoxicity (7.3%). Raised pretreatment AST/ALT (odds ratio [OR] 3.6, 95% confidence interval [CI]: 1.7 to 7.7) and hepatitis B surface antigen (HBsAg) seropositivity at baseline (OR 4.7, 95% CI: 1.7 to 12.9) were significantly associated with an increased risk of developing hepatotoxicity. Participants with both raised AST/ALT and positive HBsAg had a higher risk (OR 19.9, 95% CI: 5.3 to 74.3) and earlier onset of hepatotoxicity than participants who did not have these conditions at baseline. Conclusions: The incidence of hepatotoxicity during IPT and ART was high. Severely immunosuppressed individuals with raised pretreatment AST/ALT or HBsAg seropositivity need closer monitoring for hepatotoxicity. | en_US |
| Affilliation | UNC-Project Malawi. Lilongwe, Malawi / Harvard T. H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, MA, USA. | |
| Affilliation | Harvard T. H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, MA, USA. | |
| Affilliation | Harvard T. H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, MA, USA. | |
| Affilliation | Harvard T. H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, MA, USA. | |
| Affilliation | University of Pennsylvania. Perelman School of Medicine. Philadelphia, PA, USA. | |
| Affilliation | Johns Hopkins University. School of Medicine. Baltimore, MD, USA. | |
| Affilliation | Johns Hopkins Project. Blantyre, Malawi. | |
| Affilliation | Harvard T. H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, MA, USA. | |
| Affilliation | Harvard T. H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, MA, USA / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Johns Hopkins Project. Blantyre, Malawi. | |
| Affilliation | Case Western Research Collaboration (JCRC). Kampala, Uganda. | |
| Affilliation | UNC-Project Malawi. Lilongwe, Malawi / North Carolina School of Medicine. Chapel Hill, NC, USA. | |
| Subject | Isoniazid | en_US |
| Subject | ART | en_US |
| Subject | Hepatotoxicity | en_US |
| Subject | HIV | en_US |
| Subject | Immunosuppression | en_US |
| e-ISSN | 1944-7884 | |
