RESUMO
INTRODUCTION: A 6-month course of isoniazid, 300 mg daily, was programmatically introduced in Eritrea in 2014 as tuberculosis preventive therapy in people living with human immunodeficiency virus (PLHIV). The rollout of isoniazid preventive therapy (IPT) in PLHIV was successful in the first 2-3 years. After 2016, rumours based on rare but real incidents of liver injuries following use of IPT spread widely across the country and created concerns amongst healthcare professionals and consumers, that ultimately caused dramatic decline in the rollout of the intervention. Decision makers have been demanding better evidence as previously conducted local studies had inherent methodological limitations. This real-world observational study was conducted to evaluate the risk of liver injury associated with IPT among PLHIV attending Halibet national referral hospital, Asmara, Eritrea. METHODS: A prospective cohort study, that consecutively enrolled PLHIV attending Halibet hospital, was conducted between 1 March and 30 October 2021. Those exposed to anti-retroviral therapy (ART) plus IPT were considered as exposed and those taking only ART were considered as unexposed. Both groups were prospectively followed up for 4-5 months with monthly liver function tests (LFTs). A Cox proportional hazard model was used to explore whether there was increased risk of drug-induced liver injury (DILI) associated with IPT. Probability of survival without DILI was also estimated using Kaplan-Meier curves. RESULTS: A total of 552 patients, 284 exposed and 268 unexposed, completed the study, with a mean follow-up time of 3.97 (SD 0.675) months for the exposed and 4.06 (SD 0.675) months for the unexposed. Twelve patients developed drug-induced liver injury (DILI), with a median time-to-onset of 35 days (interquartile range: 26.8, 60 days). All cases were from the exposed group and all except two cases were asymptomatic. The incidence rate of DILI in the exposed group was 10.6 cases per 1000 person-months and zero for the unexposed group (p = 0.002). CONCLUSION: DILI in PLHIV taking IPT was common; therefore, liver function should be closely monitored to safely administer the product. Despite high levels of deranged liver enzymes, the majority had no symptoms of DILI, emphasising the importance of close laboratory monitoring, especially during the first 3 months of treatment.
RESUMO
Purpose: In Eritrea, a 6-month isoniazid preventive therapy (IPT) was introduced in Eritrea in 2014 to prevent/reduce risk of incident tuberculosis in people living with HIV (PLHIV). The global and local uptake of IPT in newly enrolled PLHIV was reported to be low. Anecdotal reports showed that there was resistance from clinicians against its implementation. This study was therefore conducted to explore the factors that affect implementation of IPT in Eritrea from the perspectives of healthcare professionals. Materials and Methods: An exploratory qualitative study that used a framework content analysis using inductive approach was employed. Data were collected from a sample of HIV care clinic prescribers from regional and national referral hospitals through in-depth interviews. Senior program officers were also interviewed as key informants. A conceptual framework model was developed using a root cause analysis. Results: Overall, five themes and 13 sub-themes emerged from the in-depth interviews with healthcare professionals and key informants. Several multi-level causes/factors related to the healthcare system, HIV control program, healthcare professionals, patients and the product were identified as barriers to the implementation of IPT. Information gap on IPT and fear of isoniazid-induced liver injury were identified as the main reasons for the reluctance in administering IPT. It was observed that healthcare professionals had significant information gap that resulted in rumors and doubts on the benefits and risks of IPT, which ultimately caused reluctance on its implementation. Inadequate planning and operationalization during the introduction of IPT and inadequate laboratory setups were found to be the possible root causes for the aforementioned central problems. Conclusion: The root causes/factors for the limited implementation of IPT in Eritrea were mainly related to the HIV control program and the healthcare system. Adequate planning, operationalization and capacitation of the existing laboratory setups are recommended for a successful implementation of IPT.
RESUMO
INTRODUCTION: A 6-month isoniazid as tuberculosis preventive therapy (TPT) for people living with HIV (PLHIV) was nationally introduced in Eritrea in 2014. However, its effectiveness in preventing tuberculosis (TB) and duration of protection was questioned by physicians. This study was, therefore, conducted to evaluate the impact of the isoniazid preventive therapy (IPT) primarily on the prevention of TB and duration of its protection in PLHIV. METHODS: A retrospective cohort study was conducted that selected all eligible PLHIV attending HIV care clinics in all national and regional referral hospitals in Eritrea. Data was collected from patients' clinical cards using a structured data extraction sheet. The association between use of IPT and outcomes of interest was assessed using a Cox proportional hazard regression model and Kaplan-Meier curve. RESULTS: A total of 6803 patients were selected, which accounted for 75% of all PLHIV-accessing HIV care clinics in Eritrea. About 76% of patients were exposed to IPT while the remaining 24% were unexposed. The mean follow-up time was 4.9 years (SD 1.4). The incidence rate of TB was 1.7 and 10 cases per 1000 person-years in the exposed and unexposed, respectively. The unexposed had a higher risk of incident TB (adjusted hazard ratio [aHR] 3.75, 95% confidence interval [CI] 2.89, 6.13) and all-cause mortality (HR 2.41, 95% CI 1.85, 3.14) compared to the exposed. A Kaplan-Meier curve showed that the exposed group had a higher TB-free follow-up probability (98.8%) compared to the unexposed (95%) at 65 months of follow-up (p < 0.001). IPT protection decreased rapidly 6 months after isoniazid completion. CONCLUSION: Use of a 6-month isoniazid as TPT was found to be effective in reducing incident TB in PLHIV-accessing HIV care clinics in Eritrea. However, the protection appeared to diminish soon, namely 6 months after completion of isoniazid, which warrants immediate attention from policy makers.
