Tolerability of Isoniazid Preventive therapy Among HIV infected Cohort in Nigeria Folajinmi Oluwasina Strategic Information Unit AIDS Healthcare Foundation, Nigeria

Outline Introduction Aims and Objectives Methods Exclusion and inclusion criteria Results

Introduction It has been known for many years that (IPT) for PLHIV prevents TB. WHO recommends that PLHIV who are unlikely to have active TB should receive at least 6 months of IPT as part of a comprehensive package of HIV care Treatment of Latent Tuberculosis Infection with isoniazid is an inexpensive, effective method. Its’ effectiveness in preventing the development of active disease is an essential strategy for eliminating tuberculosis (TB) among people living with HIV. HIV infection is the strongest risk factor for a person to develop tuberculosis, and TB is responsible for over a quarter of all AIDS-related deaths worldwide.

Introduction Cont’d The effects of IPT augment the effects of ART on reducing the incidence of TB. Although IPT uptake is increasing, fewer than 25% of persons living with HIV and who are in care are receiving it (WHO, 2016) However, there are concerns regarding the application of isoniazid (INH) due to the potential for hepatotoxicity.

WHO Three I’s for TB/HIV Collaboration Establish intensified TB case finding Introduce Isoniazid (INH) preventive therapy for Latent Tuberculosis Infection (LTBI) Ensure TB infection control in health care and congregate settings

Aims and Objectives To determine the incidence of adverse hepatic events after IPT commencement in a cohort of HIV infected patients. Adverse hepatic events were defined as elevations in liver enzymes which required IPT discontinuation.

Methods A retrospective cohort study using existing data captured during routine clinical visit at HIV clinics in Nigeria. Laboratory test investigations conducted are recorded in the OpenMRS database. Sample size -942 patients Inclusion criteria for the analysis were patients who were commenced on Isoniazid Prevention Therapy between April 2012 and April 2017.

Patients who received IPT People at high risk for TB such as: Adults & adolescents (including pregnant mothers) living with HIV (Pre-ART & on ART)” Children living with HIV (Pre-ART & on ART) Children contacts of active TB cases

Exclusion Criteria Signs of active liver disease or history of INH-induced hepatitis or heavy alcohol use Symptoms & signs suggestive of TB Patient on TB treatment Patients who have been on ART for three months or less

Results Data from 942 patients commenced on Isoniazid Prevention Therapy was analysed with 509 (54%) were females while 433 (45.9%) were males. The median age of the participants at the time IPT was started was 16 (range 1 - 69) years of age. The mean age of the patients was 19 (SD = 16) years. The mean duration of IPT use was 148 (SD = 43, range = 1 - 349) days.

Patient Characteristics (N = 942) Variable N(%) Sex Female Male 509 (54%) 433 (45.9%) Age at IPT start (years) Mean age 16 (1- 69)

337 (69.4%) of the participants had ALT within normal limits 148 (30.5%) had Elevated ALT after IPT commencement. Sixty two patients (6.6%) developed adverse hepatic events which required discontinuation of IPT after a median duration of 84 (range 1 - 149) days.

ALT Elevations severity (N =148) Variable N(%) Grade 1 and 2 ALT elevations, n (%) Median ALT (IQR) Median time to grade 1 or 2 elevation (weeks) 114 (77) 66.05 (39 - 111) 12 (8 – 19) Grade 3 and 4 ALT elevations, n (%) Median time to grade 3 or 4 elevation (weeks) Incidence 34 (23) 315 (214 – 357) 12 (9 - 16)

Results Incidence of adverse events while on IPT was 20.5 per 100 person-years (CI: 15.0-27.3). The median and mean age for patients who developed adverse hepatic events to IPT was 10 (range = 1 - 65) years and 19 (SD = 18) years of age respectively. Forty three (69.3%) of the participants who had adverse hepatic events were female.

Discussion Evidence that giving IPT as a surrogate for lifelong treatment for PLHIV is beneficial in setting with a high prevalence of TB and a high likelihood of transmission. Incidence of IPT related adverse hepatic complication were high among younger patients. We recommend vigilant monitoring of liver enzymes for patients receiving IPT.

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