Description of HIV-Infected Persons in Botswana Who Developed Active Tuberculosis during or after Isoniazid Preventive Therapy (IPT): A Retrospective Record Review
Background: Tuberculosis (TB) remains a major cause of morbidity and mortality among people living with HIV, particularly in high TB/HIV burden settings. Botswana introduced Isoniazid Preventive Therapy (IPT) for people living with Human Immunodeficiency Virus (HIV) to reduce the risk of progression from latent TB infection to active TB disease. This study describes IPT programme records and the characteristics and outcomes of HIV-infected persons who developed active TB during or after IPT exposure. Methods: A retrospective record review using IPT and TB programme registers from 24 health facilities in eight districts in Botswana. The uploaded dataset contained 1240 IPT-exposed records, classified as IPT completers, IPT defaulters, or persons who developed active TB during or after IPT exposure. Analyses were: 1) IPT programme completion/defaulting classified as completers or defaulters, and 2) TB treatment outcomes classified as g developed TB. Frequencies, proportions, means, medians, and exact 95% confidence intervals were calculated, and modified Poisson regression estimated risk ratios for common binary outcomes. Results: Of 1240 IPT-exposed records, 352 (28.4%) were IPT programme completers, 655 (52.8%) were defaulters, and 233 (18.8%) developed active TB during or after IPT exposure. Among the 1007 programme completion/defaulting records, IPT completion was 35.0% (352/1007; 95% CI 32.0 - 38.0). Male sex was associated with lower IPT completion compared with female sex (adjusted risk ratio [aRR] 0.73; 95% CI 0.61 - 0.88). Among 233 developed-TB records, 150 (64.4%) were female, median age was 37 years (IQR 32 - 43), 206 (88.4%) were new TB cases, and 162 (69.5%) had pulmonary TB. TB treatment outcomes were documented for 196/233 (84.1%) records. Among documented outcomes, 163/196 (83.2%; 95% CI 77.2 - 88.1) completed TB treatment; 17 (7.3%) died, 12 (5.2%) defaulted, 4 (1.7%) failed treatment, and 37 (15.9%) were not evaluated. In adjusted models, sex, age, Antiretroviral Therapy (ART) status, and disease classification were not strongly associated with documented TB treatment success, but incomplete records and missing ART data make this finding uncertain. Conclusions: Age showed a small link to treatment success in the sensitivity model, but incomplete records and missing ART data make this finding uncertain. IPT programme non-completion was common and was more frequent among men and younger adults. Among persons who developed TB after/during IPT exposure, most had new pulmonary TB disease, and most
References
[1]
Hamada, Y., Berkin, H., Getahun, H., Tadesse, B.T. and Ford, N. (2021) HIV-Associated Tuberculosis. InternationalJournalofSTD&AIDS, 32, 780-790. https://doi.org/10.1177/0956462421992257
[2]
Olajide, O.S., Okonkwo, P., Ajayi, O., Adetoye, D., Ogunsola, O.O., Ogundele, O., et al. (2024) Predictors of Tuberculosis Treatment Outcomes among People Living with HIV in Some States in Nigeria. ThePanAfricanMedicalJournal, 47, Article No. 149. https://doi.org/10.11604/pamj.2024.47.149.35719
[3]
Mekonen, H., Negesse, A., Dessie, G., Desta, M., Mihiret, G.T., Tarik, Y.D., et al. (2024) Impact of HIV Coinfection on Tuberculosis Treatment Outcomes in Ethiopia: A Systematic Review and Meta-Analysis. BMJOpen, 14, e087218. https://doi.org/10.1136/bmjopen-2024-087218
[4]
World Health Organization (2022) HIV-Technical Work. https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/treatment/tuberculosis-hiv
[5]
World Health Organization (2023) Background and Burden of HIV-Associated TB. TB Knowledge Sharing Platform, Consolidated Guidelines, World Health Organization.
[6]
Kenyon, T.A., Copeland, J.E., Moeti, T., Oyewo, R. and Binkin, N. (2000) Transmission of Mycobacterium Tuberculosis among Employees in the US Government Office in Gaborone, Botswana. International Journal of Tuberculosis and Lung Disease, 4, 962-967.
[7]
Botswana National Tuberculosis Programme (2009) Evaluation Report. Ministry of Health, Gaborone, Botswana.
[8]
Raviglione, M.C., Dixie, E., Snider Jr. D.E. and Kochi, A. (1997) Global Epidemiology of Tuberculosis: Morbidity and Mortality of a Worldwide Epidemic. JAMA, 273, 220-226. https://doi.org/10.1001/jama.1995.03520270054031
[9]
Cantwell, M.F., and Binkin N.J. (1997) Impact of HIV of Tuberculosis in sub-Saharan Africa: A Regional Perspective. International Journal of Tuberculosis and Lung Disease, 1, 205-214.
[10]
Joint United Nations Programme on HIV/AIDS (2004) Botswana: Epidemiological Fact Sheet on HIV/AIDS and Sexually Transmitted Diseases.
[11]
Gammino, M.V., Mboya, J.J., Samandari, T., Sheth, A., Almquist, J., Nkubito, G., Jimbo, W., Obita, G., Roles, T.H., Wells, .CD., Kilmax, P.H. and Nelson, L.J (2004) Baseline Evaluation of Routine HIV Testing among Tuberculosis Patients in Botswana. International Journal of Tuberculosis and Lung Disease, 12, S92-S94.
[12]
Botswana National Tuberculosis Programme (2011) Tuberculosis Treatment Guidelines, Ministry of Health, Gaborone, Botswana.
[13]
World Health Organization (2023) Global Tuberculosis Report 2023. World Health Organization.
[14]
Statistics Botswana, National AIDS and Health Promotion Agency (NAHPA) and Ministry of Health (MoH) (2023) The Fifth Botswana AIDS Impact Survey 2021 (BAIS V) Report. Government of Botswana. https://www.unicef.org/botswana/reports/fifth-botswana-aids-impact-survey-2021-bais-v-report
[15]
Centers for Disease Control and Prevention (2023) Reported Tuberculosis in the United States, 2022. U.S. Department of Health and Human Services.
[16]
World Health Organization and UNAIDS (1998) Policy Statement on Preventive Therapy Against Tuberculosis in People Living with HIV. World Health Organization.
[17]
World Health Organization (2004) WHO Policy on Collaborative TB/HIV Activities: Guidelines for National Programmes and Other Stakeholders. World Health Organization. https://www.who.int/publications/i/item/9789241503006
[18]
World Health Organization (2012) Global Tuberculosis Control: Epidemiology, Strategy, Financing. WHO Report.
[19]
World Health Organization (2024) WHO Consolidated Guidelines on Tuberculosis. Module 6: Tuberculosis and Comorbidities. 2nd Edition, World Health Organization.
[20]
Ministry of Health and Wellness (2023) The Botswana 2023 Integrated HIV Clinical Care Guidelines. Ministry of Health and Wellness.
[21]
Department of HIV/AIDS Prevention and Care (2008) Botswana HIV/AIDS Treatment Guidelines. Ministry of Health, Gaborone, Botswana.
[22]
Akolo, C., Adetifa, I., Shepperd, S. and Volmink, J. (2010) Treatment of Latent Tuberculosis Infection in HIV Infected Persons. CochraneDatabaseofSystematicReviews, No. 1, CD000171. https://doi.org/10.1002/14651858.cd000171.pub3
[23]
Sibanda, T., Tedla, Z., Nyirenda, S., Agizew, T., Marape, M., Miranda, A.G., et al. (2013) Anti-Tuberculosis Treatment Outcomes in HIV-Infected Adults Exposed to Isoniazid Preventive Therapy in Botswana. TheInternationalJournalofTuberculosisandLungDisease, 17, 178-185. https://doi.org/10.5588/ijtld.12.0314
[24]
Samandari, T., Agizew, T.B., Nyirenda, S., Tedla, Z., Sibanda, T., Shang, N., et al. (2011) 6-Month versus 36-Month Isoniazid Preventive Treatment for Tuberculosis in Adults with HIV Infection in Botswana: A Randomised, Double-Blind, Placebo-Controlled Trial. TheLancet, 377, 1588-1598. https://doi.org/10.1016/s0140-6736(11)60204-3
[25]
Ministry of Health (2004) Isoniazid Preventive Therapy Programme Guidelines. National Tuberculosis Control Programme, Gaborone, Botswana.
[26]
World Health Organization (2010) Global Tuberculosis Control. Surveillance, Planning and Financing. WHO Press.
[27]
Mills, H.L., Cohen, T. and Colijn, C. (2013) Community-Wide Isoniazid Preventive Therapy Drives Drug-Resistant Tuberculosis: A Model-Based Analysis. ScienceTranslationalMedicine, 5, 180ra49. https://doi.org/10.1126/scitranslmed.3005260
[28]
Eurien, D., Okethwangu, D., Aliddeki, D.M., Kisaakye, E., Nguna, J., Bulage, L., et al. (2024) Low Completion Rate for the 6-Months Course of Isoniazid Preventive Therapy among People Living with HIV, North Eastern Uganda, 2015-2017. ThePanAfricanMedicalJournal, 48, Article No. 122. https://doi.org/10.11604/pamj.2024.48.122.36745
[29]
Robert, M., Todd, J., Ngowi, B.J., Msuya, S.E., Ramadhani, A., Sambu, V., et al. (2020) Determinants of Isoniazid Preventive Therapy Completion among People Living with HIV Attending Care and Treatment Clinics from 2013 to 2017 in Dar Es Salaam Region, Tanzania. a Cross-Sectional Analytical Study. BMCInfectiousDiseases, 20, Article No. 276. https://doi.org/10.1186/s12879-020-04997-6
[30]
Matakanye, H. and Mboweni, S.H. (2024) Factors Influencing the Uptake of Isoniazid Tuberculosis Preventive Therapy among Eligible HIV Patients in Africa: A Systematic Review. TheOpenPublicHealthJournal, 17, e18749445313348. https://doi.org/10.2174/0118749445313348240809114910
[31]
Amanya, I., Muhoozi, M., Aruhomukama, D., Ssebagereka, A. and Mugambe, R. (2023) Isoniazid Preventive Therapy Completion and Factors Associated with Non-completion among Patients on Antiretroviral Therapy at Kisenyi Health Centre IV, Kampala, Uganda. PLOS ONE, 18, e0277739.
[32]
Little, K.M., Khundi, M., Barnes, G.L., Ngwira, L.G., Nkhoma, A., Makombe, S., et al. (2018) Predictors of Isoniazid Preventive Therapy Completion among Adults Newly Diagnosed with HIV in Rural Malawi. TheInternationalJournalofTuberculosisandLungDisease, 22, 371-377. https://doi.org/10.5588/ijtld.16.0836
[33]
Samandari, T., Agizew, T.B., Nyirenda, S., Tedla, Z., Sibanda, T., Mosimaneotsile, B., et al. (2015) Tuberculosis Incidence after 36 Months’ Isoniazid Prophylaxis in HIV-Infected Adults in Botswana. AIDS, 29, 351-359. https://doi.org/10.1097/qad.0000000000000535
[34]
Ministry of Health (2009) Isoniazid Preventive Therapy Progress Report.
[35]
Nidoi, J., Pulford, J., Wingfield, T., Rachael, T., Ringwald, B., Katagira, W., et al. (2024) Finding the Missing Men with Tuberculosis: A Participatory Approach to Identify Priority Interventions in Uganda. HealthPolicyandPlanning, 40, 1-12. https://doi.org/10.1093/heapol/czae087
[36]
World Health Organization (2021) WHO Global Report. Global Tuberculosis Report 2021. https://www.who.int/publications
[37]
UNAIDS (2011) Joint Programme on HIV/AIDS. World AIDS Day Report. http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2011/JC2216_WorldAIDSday_report_2011_en.pdf
[38]
Lawn, S.D., Wood, R., De Cock, K.M., Kranzer, K., Lewis, J.J. and Churchyard, G.J. (2010) Antiretrovirals and Isoniazid Preventive Therapy in the Prevention of HIV-Associated Tuberculosis in Settings with Limited Health-Care Resources. TheLancetInfectiousDiseases, 10, 489-498. https://doi.org/10.1016/s1473-3099(10)70078-5
[39]
World Health Organization (2025) Global Tuberculosis Report 2025. World Health Organization.
[40]
Sithole, N., Nkosi, B., Seeley, J., Barnabas, R.V., Siedner, M.J. and Moshabela, M. (2024) “I Didn’t Reveal My ART Status Because I Didn’t Have Money to Fetch the Transfer Letter”—Understanding Lack of Treatment Disclosure at Presentation to Care in South Africa: A Qualitative Study. AIDSandBehavior, 29, 715-724. https://doi.org/10.1007/s10461-024-04553-2
[41]
Marzinke, M.A, Clarke, C., Wang, L., Cummings, V., Liu, T.-Y., Piwowar-Manning, E., et al. (2013) Nondisclosure of HIV Status in a Clinical Trial Setting: Antiretroviral Drug Screening Can Help Distinguish Between Newly Diagnosed and Previously Diagnosed HIV Infection. AIDS, 29, 351-359.
[42]
World Health Organization (2011) Global Tuberculosis Control. Surveillance, Planning and Financing. WHO Press.
[43]
Etoori, D., Wringe, A., Renju, J., Kabudula, C.W., Gomez-Olive, F.X. and Reniers, G. (2020) Challenges with Tracing Patients on Antiretroviral Therapy Who Are Late for Clinic Appointments in Rural South Africa and Recommendations for Future Practice. GlobalHealthAction, 13, Article 1755115. https://doi.org/10.1080/16549716.2020.1755115
