Strengthening drug safety to increase use of preventive treatment for tuberculosis in Zimbabwe
Tuberculosis (TB) is the second leading cause of death from a single infectious agent, next to COVID-19 worldwide. People who become sick with TB are living with the active form of the disease, however, many people may be infected with TB and not know it. Treating latent TB infection (LTBI)—when someone is infected but not sick—is critical to prevent the development of active TB disease and spread.
In recent years, newer and better LTBI treatments with shorter duration and fewer side effects, have been developed. Treatment of LTBI with TB preventative therapy (TPT) in high-risk populations remains a cost-effective strategy for reducing TB diseases and deaths.
Zimbabwe experiences a high rate of TB infection with 199 per 100,000 people infected with the disease. This is exacerbated by a 60 percent co-infection incidence of TB/HIV.  People living with HIV and household contacts of those infected with TB are at increased risk of developing active TB disease and are prioritized for TPT in Zimbabwe.
In 2012, Zimbabwe adopted Isoniazid Preventive Therapy (IPT) as the preferred TPT regimen. However, in 2018, only 27 percent of people living with HIV and 30 percent of eligible child contacts were enrolled for treatment— far less than the national target. Many factors contributed to the low uptake including an inadequate number of healthcare workers trained in administering TPT, low awareness among beneficiaries, poor supply chain management of isoniazid and ancillary medicines, and limited monitoring of drug safety and side effects. Low IPT completion rates hampered the country’s efforts to reduce infection.
The Clinton Health Access Initiative (CHAI) Zimbabwe has been supporting the Ministry of Health and Child Care (MoHCC) in enhancing access to optimal TB and HIV treatment by scaling up:
- Availability and use of shorter TPT regimens including 3HP (isoniazid and rifapentine taken once weekly for three months) as the preferred TPT regimen for people living with HIV and household contacts of TB-confirmed patients.
- Optimal use of dolutegravir (DTG)-based regimens for adults and more recently for children for the treatment of HIV.
- Advanced HIV Disease (AHD) management and service delivery.
Ensuring drug safety has been a key component of CHAI’s implementation strategies to help prevent and/or treat adverse events and improve patient care. Monitoring adverse effects of treatment also helps smooth the transition and adoption of new regimens.
The Medicines Control Authority of Zimbabwe (MCAZ) oversees drug safety in partnership with the MoHCC and all major stakeholders from the private and public sectors. In high-burden TB/HIV nations like Zimbabwe, robust drug surveillance is even more important and strongly recommended. Strong drug surveillance systems in low- and middle-income countries not only help to prevent and control adverse health events but also encourage a more patient-centered approach to new regimens, fostering faster uptake of new drugs. Studies have also indicated that health systems that center patient drug experiences are more quickly able to identify adverse health events than those that are health worker-centered. Drug safety monitoring is required to track adverse events and ensure that antiretroviral (ARV) and anti-TB drugs are dosed appropriately based on the patient’s age and weight. In line with Zimbabwe’s national pharmacovigilance (PV) plan, it is important that while promoting the uptake of new HIV and TB regimens, we identify and manage adverse events and guarantee quality of care.
In 2021, CHAI in collaboration with MoHCC and MCAZ, conducted medicine safety monitoring and reporting trainings at 24 sites for TPT, pediatric DTG, and AHD therapeutics, training a total of 414 healthcare workers (HCWs). The trainings reached half of CHAI-supported TB/HIV sites, all HCWs in primary healthcare institutions, and 30 percent of HCWs in secondary healthcare facilities. In addition, all HCWs at opportunistic infection (OI) and TB entry points received training. The project supported the expansion of e-reporting by upskilling at CHAI focal sites on how to utilize digital tools to track patient adverse events. We used advocacy, communication, and social mobilization strategies to help enhance the detection of adverse occurrences and referral to medical facilities for treatment when necessary.
CHAI, MCAZ, and MoHCC collaborated to develop/update job aids and information, education, and communication (IEC) materials on common drug adverse events associated with optimal HIV and TB medicines, such as DTG 10mg, L-Amb, 3HP, 5FC, and supplements such as magnesium. Development of IEC materials, including job aids, and standard operating procedures (SOPs) for healthcare and community workers began in 2021 and is expected to finish in 2022.
The partnership between CHAI, MoHCC, and MCAZ is projected to improve TPT usage to help the country reach its national target. Use of 3HP improved from zero in 2019 to 49 percent in 2021, with over 15,000 patients enrolled on 3HP across 20 CHAI-supported sites. TPT coverage improved from 1.1 percent in 2019 to 7.8 percent in between 2020 and 2021 among HIV patients taking antiretroviral therapy (ART) regularly and from 25.2 percent in 2018 to 55 percent among those newly taking ART between 2019 and 2021. Treatment completion also rose exponentially from 26 percent in 2019 to 93 percent in 2021. TPT adverse event reporting improved from scanty to robust documentation with the right systems in place, resulting in fewer incidences of adverse events reported. The most reported side effects were skin irritations and vomiting. Most of these issues were tolerated, and patients continued to take TPT despite the adverse events.
In addition, mentorship and capacity building on recognizing and monitoring drug safety resulted in improved reporting of adverse drug reactions and higher quality reports; 233 adverse events were reported in 2021 with the following suspected medicines: 107 ARVs, 91 anti-TB drugs, one antimalarial drug, and 34 other important drugs.
This collaboration continues in 2022, with the goal of increasing capacity building on drug safety to all CHAI-supported facilities and beyond. The alliance intends to create a strong framework for drug safety that can support and maintain the smooth transition, adoption, and uptake of new TB/HIV medications; interconnected drug safety systems that feed into GxAlert (electronic results notification and dissemination system linked to the GeneXpert platform that diagnoses TB), laboratory information systems (LIMS), electronic health records (EHR), electronic patient monitoring systems (EPMS), district health information systems version 2 (DHIS2) platforms, and empowered community systems that demand TPT services. These strategies will go a long way to improve clinical patient monitoring and patient safety, more patients receiving and completing treatment to save lives and prevent transmission.
As we commemorate World TB Day, it is important to highlight the importance of adverse drug reaction monitoring in sustaining improved treatment experiences within the TB space.
 World Health Organization. Global Tuberculosis Report 2021.
 WHO. Tuberculosis key facts 2020 [Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis.
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 Egberts GPG Smulderes M, De Konig FHP et al. Can adverse drug reactions be detected earlier?: a comparison of reports by patients and professionals. British Medical Journal 1996; 313: 530 – 31.
 Medicines Control Authority of Zimbabwe, 2022, Medicines Information Bulletin