Incidence and patterns of adverse drug reactions in HIV positive patients on isoniazid tuberculosis preventive therapy at Kenyatta National Hospital.

Abstract

BACKGROUND: Isoniazid tuberculosis preventive therapy (IPT) is use of isoniazid at a dose of 5mg/kg/day (max 300mg) in adults for a period of 6 to 9 months to prevent reactivation of active tuberculosis (TB). Isoniazid tuberculosis preventive therapy has been recommended by World Health Organization (WHO) since 1998 and by the end of 2016; over 300,000 patients had been enrolled on IPT in Kenya which represents 33% of all the People Living with HIV. At the time of the study, isoniazid was the only available treatment for latent tuberculosis infection although clinical trials on rifapentine and isoniazid combination were being conducted. Adverse drug reactions can occur during IPT which can lead to increased morbidity and mortality, reduced adherence and treatment failure. Several risk factors increase toxicity to IPT. OBJECTIVES: The main objective of this study is to measure the incidence and identify risk factors for adverse drug reactions in HIV positive patients on isoniazid preventive therapy. METHODS: Two study methods were used; comparative cross sectional study and longitudinal cohort study. The study was carried out at Kenyatta National Hospital Comprehensive Care Centre from April to September 2018. Data collection was divided into three parts; patients interview using a structured questionnaire, abstraction of information from the patient files and database review. Data analysis was done using STATA software version 13. RESULTS: Longitudinal cohort study was conducted for 592 patients who had completed IPT. Mean age was 45.1 years and majority were females (66%). ALT measurements were recorded for 436 patients at baseline and during IPT. Incidence of liver disease during IPT was 4.4%. The prevalence of abnormal ALT levels increased from 11.7% at baseline to 15.6% during IPT (p=0.056). Majority of the patients had mild hepatotoxicity (13.8%), those with moderate were 1.4% and 0.5% had a life threatening hepatotoxicity. The prevalence of all levels of liver severity increased during IPT. There was a significant improvement of renal function during IPT as compared to the baseline by 4.8% (p=0.036). Creatinine measurements were also obtained for 562 patients at baseline and during IPT. There was an increase in eGFR from a median of 76.3 ml/min/1.73m2 at baseline to 80.5 ml/min/1.73m2 during IPT (p<0.001). Male patients had significantly higher prevalence of liver failure (27.5%) compared to females (9.9%), p< 0.001. Patients with renal failure were significantly older (mean 47.2 years) compared to those with normal eGFR (mean 40.3 years), p<0.001. Females had a higher prevalence of renal failure (81.8%) compared to males (44.8%), p<0.001. In the comparative cross sectional study, 264 patients were interviewed and their mean age was 41.3 years while majority were females (56.8%). Patients who had used IPT were more likely to report any ADR sign (36.9%) compared to those who had never used IPT (25.2%), OR 1.7 (95% CI 1.2-3.0), p=0.043. Main ADRs experienced during IPT were; numbness, tingling feet/burning sensation (8.7%), skin rash (6.7%), gastrointestinal (5.3%) and hepatotoxicity (4.7%). For the majority (73.9%) no action was taken for the ADRs while IPT was withdrawn in 24.6%. Conclusion: Adverse drug reactions are likely to occur during IPT. Incidence of liver disease was 4.4% in patients on IPT and the prevalence was significantly higher in males compared to females (p< 0.001). There was a significant improvement in renal functions in 4.8% of the patients on IPT with females and older patients experiencing higher prevalence of renal disease. Close monitoring of high risk groups such as the elderly, diabetic and hypertensive patients is therefore necessary to ensure their safety during IPT.