Suspected adverse drug reactions of isoniazid preventive therapy in HIV-positive patients at three regional hospitals: prevalence, associated factors, management and reporting

Abstract

Background Tuberculosis (TB) is the 10th leading cause of death globally and the leading cause of death from a single infectious agent among people living with HIV (PLHIV). Uganda is among the 30 high burden TB countries and is also faced with a dual HIV/TB epidemic. HIV is one of the biggest risk factors for TB infection and hence Isoniazid Preventive Therapy (IPT) is recommended for PLHIV to prevent TB. However, these patients are predisposed to adverse drug reactions (ADR) which if not managed, can cause increased mortality and morbidity. Reporting ADRs enables medicine safety monitoring though there is gross under reporting of ADRs to the National Drug Authority (NDA). Main objective We determined the prevalence, associated factors, management and reporting of suspected adverse drug reactions of isoniazid preventive therapy in PLHIV who are 10 years or older attending Naguru, Entebbe and Masaka Regional Referral Hospitals in Uganda. Methods A cross sectional study was conducted at Naguru, Entebbe and Masaka Regional Referral Hospitals following ethical approval from School of Medicine Research and Ethics Committee. Between 13th February and 27th March 2020, 660 PLHIV aged 10 years or older who had received IPT between 1st July and 31st December 2019 were recruited into the study. Participants were interviewed using a structured questionnaire and their treatment records were reviewed. Factors associated with ADRs were assessed using a modified poisson regression model with clustered robust standard errors and the main outcome variable was the occurrence of suspected ADR. Results The prevalence of suspected ADR was 50.6% (95% CI: 18% – 83%). Musculoskeletal symptoms were the most prevalent reactions (14.1%) followed by dizziness (13.0%) and peripheral neuropathy (11.4%). The independent variables associated with suspected ADRs were: female sex (aPR=0.92, p <0.001), Naguru hospital (aPR=0.91, p <0.001), Entebbe hospital (aPR=1.09, p <0.001), level of education (aPR=0.94, p <0.001), history of TB (aPR=0.93, p=0.031),good IPT adherence (aPR=1.17, p=0.001), ART regimen (aPR=1.01 p =0.001). There was no specific management given to 81.1% of the study participants who experienced a suspected ADR and only 0.003% of the ADRs were reported to NDA. Conclusion and recommendation The prevalence of suspected ADRs due to IPT was high yet the management of the suspected serious ADRs was inadequate and there was under reporting of these ADRs to NDA. We recommend routine monitoring of patients on IPT for early detection and prompt management of suspected ADRs as well as patient engagement in ADR reporting.