Zegabriel Tedla1, Minh-Ly Nguyen2, Thabisa Sibanda1, Samba Nyirenda3, Tefera B Agizew1, Sonali Girde4, Charles E Rose5, Taraz Samandari6. 1. CDC Botswana, Gaborone, Botswana. 2. Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. 3. CDC Botswana, Francistown, Botswana. 4. Division of HIV/AIDS Prevention, Atlanta, GA; ICF International, Inc, Atlanta, GA. 5. Division of HIV/AIDS Prevention, Atlanta, GA. 6. CDC Botswana, Gaborone, Botswana; Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. Electronic address: tts0@cdc.gov.
Abstract
BACKGROUND: The World Health Organization recommends 36 months of isoniazid preventive therapy (36IPT) for adults infected with HIV living in TB-endemic countries. We determined the rates and risk factors for isoniazid-associated hepatitis with the use of 36IPT. METHODS:One thousand six adults infected with HIV received 36IPT during a pragmatic randomized trial set in Botswana public health clinics providing HIV care. Enrollment exclusion criteria included jaundice or elevations of serum transaminases (ESTs) > 2.5-fold the upper limit of normal (ULN). Participants with any CD4+ lymphocyte count were eligible and receivedantiretroviral therapy (ART) when CD4+ < 200 cells/μL. 36IPT was stopped for severe hepatitis (more than fivefold ULN EST) but not for moderate hepatitis (2.5-fold to fivefold ULN EST). RESULTS: Pharmacy refill records showed 2,237 person-years of isoniazid receipt; 48% of participants initiated ART by 36 months. A total of 1.9% (19 of 1,006) of participants were diagnosed with severe hepatitis; three had jaundice and two of these developed hepatic encephalopathy. Another 3.1% (31 of 1,006) of participants experienced moderate hepatitis. Thirty-eight percent (19 of 50) of participants with moderate to severe hepatitis concomitantly received ART. Forty percent (20 of 50) of moderate to severe cases occurred within the first 2 months of IPT and during this period were not associated with receipt of ART at baseline (hazard ratio, 1.49; 95% CI, 0.20-11.1; P = .70). CONCLUSIONS: Adults infected with HIV receiving 36IPT did not have an increased incidence of moderate to severe hepatitis or hepatic encephalopathy compared with published reports among people infected with HIV, people not infected with HIV in trials or public health programs. Compared with participants not receiving ART, the risk of moderate to severe hepatitis was not increased by ART. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00164281; URL: www.clinicaltrials.gov.
RCT Entities:
BACKGROUND: The World Health Organization recommends 36 months of isoniazid preventive therapy (36IPT) for adults infected with HIV living in TB-endemic countries. We determined the rates and risk factors for isoniazid-associated hepatitis with the use of 36IPT. METHODS: One thousand six adults infected with HIV received 36IPT during a pragmatic randomized trial set in Botswana public health clinics providing HIV care. Enrollment exclusion criteria included jaundice or elevations of serum transaminases (ESTs) > 2.5-fold the upper limit of normal (ULN). Participants with any CD4+ lymphocyte count were eligible and received antiretroviral therapy (ART) when CD4+ < 200 cells/μL. 36IPT was stopped for severe hepatitis (more than fivefold ULN EST) but not for moderate hepatitis (2.5-fold to fivefold ULN EST). RESULTS: Pharmacy refill records showed 2,237 person-years of isoniazid receipt; 48% of participants initiated ART by 36 months. A total of 1.9% (19 of 1,006) of participants were diagnosed with severe hepatitis; three had jaundice and two of these developed hepatic encephalopathy. Another 3.1% (31 of 1,006) of participants experienced moderate hepatitis. Thirty-eight percent (19 of 50) of participants with moderate to severe hepatitis concomitantly received ART. Forty percent (20 of 50) of moderate to severe cases occurred within the first 2 months of IPT and during this period were not associated with receipt of ART at baseline (hazard ratio, 1.49; 95% CI, 0.20-11.1; P = .70). CONCLUSIONS: Adults infected with HIV receiving 36IPT did not have an increased incidence of moderate to severe hepatitis or hepatic encephalopathy compared with published reports among people infected with HIV, people not infected with HIV in trials or public health programs. Compared with participants not receiving ART, the risk of moderate to severe hepatitis was not increased by ART. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00164281; URL: www.clinicaltrials.gov.