Knock Out TB in PLHIV: Reinforcing TB Prevention Therapy Completion in Zambia

Authors: Rokshana Islam, Eric Mpoyi Mulumba & Beatrice Chiyokoma;Mentors:  Kwame Shanaube, Ngula Kabelenga, Douglas Mushinge, Lawrence Mwenge & Mwango Ng’uni.

Supported by: NHRA

Key Messages

  • WHO estimates that 2-3 billion people have latent TB. Even though latent TB has no signs and symptoms of TB, people are at risk of progressing to Active TB
  • The risk is 21 times higher among PLHIV than in the HIV Negative population
  • Tuberculosis remains the leading cause of death among people living with HIV
  • TB Prevention Therapy (TPT) is critical to ending disease and death among PLHIV

Problem Statement  

  • Globally,10 million people developed TB, 8.2% were PLHIV. 14.8% of TB deaths were HIV positive deaths. In Zambia, 333 out of 100 000 people develop TB. 154 out of 100 000 people that develop TB are also HIV infected. 53 out of 100 000 people that die of TB are HIV infected.
  • Anti-Retro Viral Therapy (ART) alone, does not prevent TB. In 2017, the MOH introduced TB Preventive therapy (TPT) in PLHIV. TPT in combination with ART is 60% to 90% effective in reducing risk of progression to active TB, offering immunity for 3-5 years after completion of treatment.
  • Globally, 30 million PLHIV are to be enrolled on TPT by 2022. So far, 21% of this target has been achieved. Zambia targets to enroll 95% of eligible population on TPT and ensure that 95% of those enrolled complete treatment. Recent statistics show that TPT enrolment reached 82.5% of intended target with a 70% completion rate.

Note: The orange signifies the desired target for the MOH in Zambia

1 WHO Consolidated Guidelines -2020

2 TB Statistics WHO 2019

Factors Affecting Completion of TB Preventive Therapy

Studies have shown significant difference on risk of progression to active TB on efficacious TB prevention treatment regimens between the time a client starts treatment to the time they complete treatment. The findings are summarised in the table below.

Risk of Progression to Active at Different Levels of Completion

Regimen Before CompletionCompleted Treatment
INH60.21 (3-5 months)0.69 (6 months)
3HP0.48 (2 months)0.98 (3 months)
3HR0.47 (2 months)0.96 (3 months)

-Findings in the table above show that clients who complete TB preventive treatment, have a much reduced chance of developing active TB.

4 National TB and Leprosy Program Data-2020,                                                                                 

5 Jacobson k. B.,  et. Al

6 Robert M., et. Al

Policy Options

  • Current standard of TB preventive therapy in Zambia
  • Reduces risk for TB by 69% in PLHIV
  • 75% treatment completion rate
  • Safe for pregnant & breastfeeding mothers, and children
  • Limited by low treatment completion rates and adverse events when compared to other regimens
  • Better drug tolerability/lowest side effect profile
  • Compatible with most ART Regimens used in Zambia
  • Much higher treatment completion rate-78%
  • Reduced risk to TB by 98% in PLHIV
  • Easier to administer on a fixed dose combination
  • Not proven safe in pregnant & breastfeeding mothers and children <2 years
  • Requires barrier contraceptive in women of reproductive age
  • Alternative short course TPT regimen that combines INH and RIF
  • Proven safe to be taken by pregnant & breastfeeding mothers and children
  • Dosing adjustments required for Lopinar, Ritonavir and DTG
  • Has the lowest completion rate-72% when compared to other policy options

4 National TB and Leprosy Program Data

7 Doan T.N., et al 2019

8 Pease C., et el 2017

Economic Evaluation Analysis

Cost Effectiveness Results (Per 1000)
Drug RegimenCostsIncremental CostsEffectiveness (Cases)Incremental EffectsICER

The economic analysis demonstrates that 3HR is likely to be most cost effective relative to the Standard of Care (IHN). Specifically, 3HR would cost an additional $79.1 per patient treated compared to 3HP that costs $151.5 to treat an additional patient.

Note: The calculations in the above table were based on the Zambia Tuberculosis National Operational Plan 2017-2021 Costing document and the MOH Data Quality Management System Budget. Included in the calculations are drug costs and all elements (freight, clearance, point of distribution to the health facility)

Recommendations and next steps

  • Migrate to 3HP with better drug tolerability, and higher completion rates for the eligible population
  • Pregnant and breastfeeding mothers, and children to migrate from INH6 to 3HR which is proven safe with a much higher completion rate compared to INH6
  • Recommendations above to be implemented along aside strengthened monitoring and evaluation systems and a robust communication strategy emphasizing the benefits of TB Prevention Therapy.

Required Actions

  • Identify and work with relevant stakeholders to engage pharmaceutical companies to address the high drug (Rifapentine) costs
  • Conduct research on the safety of 3HP for pregnant and breastfeeding women and children
  • Update TB treatment guidelines to reflect proposed regimen change (from INH6 to 3HP)
  • 3HP treatment roll out plan developed and shared with relevant stakeholders
  • Strengthen monitoring and evaluation systems to improve data quality for TPT indicators
  • Develop a communication strategy on TB prevention targeting health workers, PLHIV and the general population

Note: These recommendations are based on the studies conducted in South Africa, Tanzania, and Uganda and the WHO Guidelines., consultations with CDC Zambia, USAID and MOH National TB Program and expert opinion.


References/ Resources

2020 WHO Consolidated Guidelines

Tuberculosis Statistics-Zambia Profile (WHO, 2019)

Zambia Ministry of Health Guidelines for the Management of Latent Tuberculosis Infection. March 2019 Second Edition

The National Tuberculosis and Leprosy Program Data (2020 TPT Data Review Meeting)

Jacobson K. B., Niccolai L., Mtungwa N., Moll A.P., and Shenoi S.V. (2017). “It’s about my life”: facilitators of and barriers to isoniazid preventive therapy completion among people living with HIV in rural South Africa. AIDS Care. 2017 jul; 29 (7): 936-942.

Robert M., Todd J., Ngoni B.J., Msuya S.E., Ramadhani A., Sambu V., Jerry I., Muyuni M.R., mahande M.J., Ngocho J.S., and Maokola W., (2020): Determinants of isoniazid preventive therapy completion among people living with HIV attending care and treatment clinics from 2013 to 2017 in Dares Salaam Region, Tanzania. A cross-sectorial analytical study. BMC Infectious Diseases. 276 (2020)

Doan T.N., Fox G.J., Mechan M.T., Scott N., Ragonnet r., Viney K., Trauer J.M., and mcBryde E.S. (2019): Cost effectiveness of 3 months of weekly rifapentine and isoniazid compared with other standard treatment regimens for latent tuberculosis infection: a decision analysis stud. Journal of Antimicrobial Chemotherapy. 2019; 74: 218-227

Pease C. hutton B., Yazdi F., Wolfe D., Hawel C., Quach P., Skidmore B., Moher D., and Alvarez G.G (2017). Efficacy and completion rates of rifapentine and isoniazid (3HP) compared to other treatment regimens for latent tuberculosis infection: a systematic review with network meta-analyses. BMC infectious Diseases (2017) 17; 265

Zambia Tuberculosis national Operational Plan 2017-2021 Costing (2017, April)

Data Quality Management System Budget (Monitoring and Evaluation Department: MOH, 2021)