Incidence of Tuberculosis disease and associated factors in children living with HIV on anti-retro viral treatment and isoniazid preventative therapy in Dar es salaam Tanzania: a retrospective cohort study.

Abstract

ABSTRACT Introduction: Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) continue to be major causes of morbidity and mortality among children due to their synergistic effects. Although significant strides have been made in reducing morbidity and mortalities due to HIV through strategies such as the '95-95-95' targets for HIV diagnosis, antiretroviral therapy (ART) initiation, and viral suppression among Children Living with HIV (CLHIV), TB remains a prevalent cause of morbidity and deaths. Isoniazid Preventive Therapy (IPT) is a critical intervention recommended by the World Health Organization (WHO) for high risk groups, including CLHIV, to treat latent TB and prevent active TB disease. Despite its established efficacy in adults, evidence supporting IPT's effectiveness in reducing TB disease and mortality in children remains scarce. Objective: This study was set to assess the impact of IPT on the incidence of TB disease and mortality among CLHIV aged 1-15 years who are on ART and attending high-volume Care and Treatment Clinics (CTCs) in Dar es Salaam, Tanzania. Methodology: A retrospective open cohort study was conducted using data from the National AIDS Control Program (NACP)—Centre of Treatment and Care (CTC) database. The study included children aged 1-15 who were newly diagnosed with HIV and enrolled in care between January 1, 2019, and December 31, 2022. The cohort consisted of 480 eligible newly diagnosed CLHIV on ART. Participants were followed up for IPT use of which 268 received IPT and 212 did not receive IPT and assessed for the development of TB disease and mortality outcomes. Results: Among the 480 participants, the median follow-up time was 6979.1 for IPT users and 1752.4 person-months for non-users. Most participants were aged 5-15 years (57.9%), with most attending Ilala Municipal Council clinics (46.3%) and Mbagala Rangi Tatu Health Centre (17.3%). A significant portion of the participants had advanced HIV (WHO clinical stages 3 and 4) (63.4%) and were underweight (26.3%). During the follow-up period, 13 CLHIV developed TB which 3 were diagnosed microbiologically, 3 clinically, 3 by chest x-ray 2 by combination of chest x-ray and microbiological evidence, most cases occurring within the first six months. vi The incidence rate of TB showed higher trends among non-IPT users (228.3 cases per 100,000 CLHIV) compared to IPT users (129.0 cases per 100,000 CLHIV) however these were not statistically significant. IPT usage significantly protected against mortality (cHR = 0.01, 95% CI: 0.001 – 0.08, P value <0.001). Most deaths occurred within the first six months of follow-up (79.6%), with an incidence rate of 1649.6 per 100,000 CLHIV. The overall mortality rate was 639.3 per 100,000 CLHIV over 7664.6 person-months. Conclusion and Recommendation: IPT used concurrently with ART significantly reduces the incidence of TB and mortality among CLHIV on ART. The incidence rate of TB was over 40% lower among IPT users, and mortality was reduced by more than 99% in the IPT group. These findings are in alignment with WHO recommendations and IPT use should be implemented consistently alongside other TB prevention strategies for all eligible CLHIV to reduce TB disease rates and improve survival outcomes effectively.