Assessing Tuberculosis Preventive Therapy (TPT) Outcomes in PLHIV: Initiation, Completion Rates and Influencing Factors within the DROP TB Cohort study in KwaZulu-Natal province, South Africa

Abstract

Introduction: Tuberculosis (TB) is a major global health concern, particularly among people living with HIV (PLHIV). The incidence of TB/HIV co-infection is particularly high in Sub-Saharan Africa, specifically in the KwaZulu-Natal province of South Africa. The World Health Organization (WHO) recommends tuberculosis preventative therapy (TPT) to prevent TB disease in PLHIV. Despite the proven benefits of TPT in reducing TB incidence and mortality among PLHIV, its implementation faces numerous challenges in high-burden areas like KwaZulu-Natal. The uptake and completion of TPT is hindered by several factors, such as logistical, structural, socio-economic, socio-demographic, behavioral, clinical, and healthcare resource challenges. This thesis study aims to assess the TPT initiation and completion rate and explore their associated factors among enrolled PLHIV newly starting or reinitiating antiretroviral therapy (ART) within the Diagnostic Routines for HIV-infected Outpatients with TB (DROP TB) cohort study, providing insights of TPT outcomes in a high TB burden setting and offering valuable implications for public health interventions and policymaking.Methods: This secondary data analysis utilized the prospective DROP TB cohort study. The participants were clinic-based PLHIV, aged 18 years and above, enrolled at two public health clinics, one peri-urban and one rural, situated in the uMkhanyakude district. The study assessed TPT initiation and completion rates among PLHIV participants who were screened for TB at the time of ART initiation or re-initiation between November 2021 and April 2024. TPT regimens provided during the study period were 6H (six months daily isoniazid, (H)) and in September 2023, 3HP (3 months weekly isoniazid (H) and rifapentine (P)) was introduced. Enrolled participants were assessed for various factors during baseline and quarterly check-in phone calls or in-person visits at months 3, 6, 9, and 12, coordinated with the participant's ART refill visits when possible. TPT initiation and completion rates were assessed using selected variables from the DROP TB dataset, including socio-demographic, behavioral, and clinical data, as well as TPT-related reasons. Quarterly follow-up interviews and medical record reviews were used to assess TPT initiation and completion. South African national guidelines recommended that clinics provide TPT to PLHIV after TB disease was excluded with TB screening. TPT completion was determined through case-by-case outcome assessments based on the completion of follow-up visits according to the medication duration of TPT regimen (6-month follow-up for 6H or 3-month follow-up for 3HP). Both univariate and multivariate analyses by modified Poisson regression were employed to identify factors associated with TPT initiation and completion. Results: Among 411 enrolled PLHIV participants, 96% (393/411) were eligible for TPT, and 75% (293/393) initiated TPT, with the majority 79% (232/293) initially receiving 6H and 21% (61/293) receiving the 3HP regimen. However, during follow-up visits, 34 6H participants restarted or changed to 3HP, resulting in a final TPT regimen distribution of 27% (80/293) on 3HP and 73% (213/293) on 6H regimen. Of the 293 PLHIV who initiated TPT, 18% (52/293) were excluded from the TPT completion analysis due to unknown TPT completion status. Among participants with known TPT completion status, less than half 42% (102/241) completed their prescribed TPT regimen. TPT initiation rates were higher among participants enrolled at the rural clinic (82% vs. 71%, aRR: 1.21, 95% CI: 1.08-1.36, p=0.001) and those who were unemployed compared to employed (65% vs. 35%, aRR: 0.87, 95% CI: 0.77-1.00, p=0.034). Notably, while 86% (25/29) of participants who were prescribed 3HP completed the regimen, only 36% (77/212) of those prescribed 6H completed the full 6-month course. TPT completion was 21% higher among males (aRR: 1.21, 95% CI: 0.78-1.88), 52% higher among unemployed participants (aRR: 1.52, 95% CI: 0.97-2.38), 32% lower among those having secondary and above education (aRR: 0.68, 95% CI: 0.43-1.09), 64% lower among those aged >50 years (aRR: 0.36, 95% CI: 0.12-1.10), compared to their respective reference groups, although these associations did not reach statistical significance. The risk of TPT non-completion was 59% lower for 3HP compared to 6H regimen in univariate analysis (RR: 0.41, 95% CI: 0.29-0.60, p<0.001) and remained significant in the multivariate analysis adjusted for age, sex, employment, education, enrollment site, and housing type (aRR: 0.42, 95% CI: 0.29-0.60, p<0.001). The strong association between 3HP and higher completion rates persisted in sensitivity analyses assuming either non-completion or completion for regimen changed participants with unknown completion status. Conclusion: Nearly three-quarters of PLHIV in this cohort started TPT along with ART, with higher rates among rural clinic enrollees and unemployed individuals, but less than half completed their regimen. The only significant predictor of TPT completion was regimen, with participants receiving 3HP more likely to complete than those receiving 6H, emphasizing the need for shorter, more patient-friendly regimens. While not statistically significant, the study found that TPT completion rates were higher among males, unemployed participants, and those aged <30 years, while completion rates were lower among those aged >50 years and with higher education levels. Given the absence of strong determinants of TPT completion beyond regimen type in our analysis, further research is needed to investigate the potential influence of healthcare system-related issues, individual patient preferences, and other factors on TPT completion rates, as the current study did not find statistically significant associations between most socio-demographic, behavioral factors and treatment completion. The study emphasizes the need to promote shorter regimens like 3HP, provide targeted counseling and support to patients at risk of non-completion, and equip healthcare facilities with resources and training to increase TPT uptake and completion rates among PLHIV in high-burden settings.