Adverse Drug Reactions Related to Isoniazid Preventive Therapy Among Persons Living With HIV on Dolutegravir-Based Regimens in Uganda Between July 2019 and March 2020.

BACKGROUND: Isoniazid preventive therapy (IPT) is recommended for the treatment of latent tuberculosis (TB) infection and is beneficial for persons living with HIV (PLHIV) even after initiation of antiretroviral therapy (ART). After the roll out of dolutegravir (DTG)-based ART in 2018, the Uganda Ministry of Health rapidly expanded IPT coverage among PLHIV. We assessed if concomitant IPT and DTG administration (C-IPT) increased the risk of IPT-related adverse drug reactions (ADRs) compared with delayed IPT administration (D-IPT).

METHODS: We abstracted data from medical records of PLHIV aged ≥18 years who initiated IPT between July 2019 and March 2020 at an HIV clinic in Kampala. IPT-ADR incidence was calculated from IPT initiation to first ADR or censoring, expressed as the number of ADRs per person-years at risk. Kaplan-Meier survival analysis and the log-rank test were used to compare ADR risk between groups. A Cox proportional hazards model estimated the adjusted effect of C-IPT on ADR incidence, and robustness was evaluated using Poisson regression with standard errors.

RESULTS: We analyzed data from 336 patients on DTG-based ART and IPT, 58% were male, with a median age of 46 years (IQR; 38-54), and 66.7% had no history of comorbidities. Overall, 193 (57.4%) reported at-least 1 IPT-related ADR during 114.72-person years of follow-up. After adjusting for age, HIV-1 viral load, and history of comorbidities, C-IPT was associated a significantly higher risk of IPT-related ADRs compared with D-IPT (adjusted Hazard Ratio 1.63, 95% CI: 1.17 to 2.26, P < 0.01). There was no difference in the proportion of patients who discontinued IPT because of ADRs in either group (2.2%, 2/95 vs. 4.2%, 10/241, P = 0.36).

CONCLUSION: Concomitant initiation of IPT and DTG-based ART was associated with a higher risk of ADRs but did not increase IPT discontinuation. Enhanced clinical monitoring is warranted for patients initiating both therapies to facilitate early detection and management of ADRs.