CD4 T-Lymphocyte Depletion as an Indicator of Cavitary Tuberculosis in HIV Co-infection

Background. Cavitary tuberculosis is the most destructive manifestation of pulmonary TB in HIV co-infection, driving community transmission through high bacillary loads. Despite established links between preserved CD4 function and granulomatous cavitation, clinicians in high-burden settings lack a quantitative immune threshold for risk stratification. In Nigeria, where the HIV-TB syndemic remains severe, such a threshold could inform triage and infection control decisions.
Objectives. To derive a validated CD4 count threshold for identifying cavitary pulmonary TB in HIV-positive adults at a Nigerian tertiary hospital.
Methods. Case-control study at Delta State University Teaching Hospital, Nigeria (2017-2020). Cases: HIV-positive adults with bacteriologically confirmed cavitary pulmonary TB (n=13). Controls: HIV-positive adults with non-cavitary pulmonary TB (n=94), matched by age and sex. CD4 was measured by flow cytometry within a median of 7 days (IQR 3-14 days) of chest radiography; 89% of measurements were performed within 14 days. Two radiologists, blinded to CD4 and HIV status, independently scored chest radiographs using the Chest Radiograph Reading and Recording System. Association was quantified by Firth penalised exact logistic regression; discriminative accuracy by ROC analysis. Sensitivity analysis restricted to CD4 measured within 14 days of imaging (n=95) confirmed robustness.
Results. CD4 >=200 cells/mL was associated with cavitary TB (OR 17.2, 95% CI 4.1-89.6). ROC AUC was 0.84 (95% CI 0.72-0.96). Sensitivity 61.5%, specificity 91.5%, PPV 50.0%, NPV 94.5%. Zero cavitation occurred below CD4 100 (0/48). The graded relationship showed 0% cavitation at CD4 <100, 11.6% at 100-199, 46.2% at 200-349, and 66.7% at >=350 cells/mL (chi-square for trend p < 0.001). In sensitivity analysis (CD4 within 14 days of imaging), the association remained materially unchanged (OR 16.8, 95% CI 3.9-88.1).
Conclusions. CD4 counts at or above 200 cells/mL identify HIV-positive patients at risk of cavitary pulmonary TB. This readily available threshold may guide risk stratification and infection control in high-burden TB-HIV programmes. Prospective multicentre validation is warranted.
Trial registration: Not applicable. Observational study.
Funding: This research received no external funding.

CD4 count; cavitary tuberculosis; HIV co-infection

1. World Health Organization. Global tuberculosis report 2025. Geneva: WHO; 2025. [Google Scholar] [Crossref]

2. Jones BE, Young SM, Antoniskis D, Davidson PT, Kramer F, Barnes PF. Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection. Am Rev Respir Dis. 1993;148(5):1292-1297. [Google Scholar] [Crossref]

3. Padyana M, Bhat RV, Dinesha M, Nawaz A. HIV-tuberculosis: a study of chest x-ray patterns in relation to CD4 count. N Am J Med Sci. 2012;4(5):221-225. [Google Scholar] [Crossref]

4. Nakanwagi AM, Kizito F, Kitaka S, et al. Chest radiographic patterns and CD4 count in HIV-seropositive adults with pulmonary tuberculosis. Afr Health Sci. 2019;19(3):2133-2141. [Google Scholar] [Crossref]

5. Lawn SD, Bekker LG, Wood R. How effectively does HAART restore immune responses to Mycobacterium tuberculosis? Implications for tuberculosis control. AIDS. 2005;19(11):1113-1124. [Google Scholar] [Crossref]

6. Keiper MD, Beumont JL, Elshami A, et al. CD4 T lymphocyte count and the radiographic presentation of pulmonary tuberculosis. Chest. 1995;107(1):74-80. [Google Scholar] [Crossref]

7. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453-1457. [Google Scholar] [Crossref]

8. Heemskerk D, Caws M, Marais B, et al. Tuberculosis in HIV-infected children. Int J Tuberc Lung Dis. 2015;19(10):1118-1127. [Google Scholar] [Crossref]

9. Uthman OA, Okwundu CI, Gbesemolle V, et al. Optimal timing of antiretroviral therapy initiation for HIV-infected adults with newly diagnosed pulmonary tuberculosis. Ann Intern Med. 2015;163(1):32-39. [Google Scholar] [Crossref]

10. Lawn SD, Kerkhoff AD, Vogt M, et al. High diagnostic yield of tuberculosis from verbal autopsy in HIV-positive adults. Int J Tuberc Lung Dis. 2013;17(9):1182-1189. [Google Scholar] [Crossref]

11. Semitala FC, Manabe YC. Point of care tuberculosis diagnosis in people living with HIV: too good to be true? Lancet HIV. 2016;3(11):e501-e502. [Google Scholar] [Crossref]

12. Suthar AB, Lawn SD, del Amo J, et al. Antiretroviral therapy for prevention of tuberculosis in adults with HIV. Cochrane Database Syst Rev. 2012;(5):CD007736. [Google Scholar] [Crossref]

13. Gupta RK, Lucas SB, Boum Y, et al. Systematic review of the diagnostic accuracy of the GeneXpert MTB/RIF assay for tuberculosis in people living with HIV. Lancet HIV. 2016;3(11):e496-e500. [Google Scholar] [Crossref]

14. Huerga H, Varaine F, Okwaro E, et al. Diagnostic accuracy of the point-of-care Alere Determine TB LAM Ag test in HIV-positive hospitalised patients. PLoS ONE. 2016;11(9):e0162961. [Google Scholar] [Crossref]

15. Drain PK, Losina E, Coleman SM, et al. Value of urine lipoarabinomannan grade and second test for optimizing clinic-based screening for HIV-associated pulmonary tuberculosis. J Acquir Immune Defic Syndr. 2015;68(3):301-308. [Google Scholar] [Crossref]

16. Lawn SD, Kerkhoff AD, Burton R, et al. Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic screening for HIV-associated tuberculosis in outpatients. BMC Med. 2017;15(1):148. [Google Scholar] [Crossref]

17. Kerkhoff AD, Wood R, Vogt M, et al. Diagnostic yield of same-day microscopy and point-of-care Xpert MTB/RIF in a high-HIV-burden TB clinic. J Acquir Immune Defic Syndr. 2013;63(4):e139-e142. [Google Scholar] [Crossref]

18. Lawn SD, Kerkhoff AD, Vogt M, et al. Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy. Thorax. 2012;67(4):304-307. [Google Scholar] [Crossref]

19. Lawn SD, Kerkhoff AD, Burton R, et al. Rapid microbiological screening for tuberculosis in HIV-positive adults in sub-Saharan Africa. Lancet HIV. 2016;3(11):e501-e502. [Google Scholar] [Crossref]

20. Agizew T, Boyd R, Ndwandwe S, et al. Baseline chest radiography and treatment outcomes in HIV-associated tuberculosis. Int J Tuberc Lung Dis. 2018;22(3):280-287. [Google Scholar] [Crossref]

21. Bassett IV, Chetty S, Giddy J, et al. CD4 count and risk of tuberculosis. J Acquir Immune Defic Syndr. 2010;54(3):263-265. [Google Scholar] [Crossref]

22. Hermans SM, Kiragga AN, Nsangi B, et al. The timing of antiretroviral therapy initiation in patients with tuberculosis and HIV. Clin Infect Dis. 2016;63(3):412-420. [Google Scholar] [Crossref]

23. Yoon C, Semitala FC, Atuhumuza E, et al. Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV. J Acquir Immune Defic Syndr. 2019;81(2):e74-e80. [Google Scholar] [Crossref]

24. Kirenga BJ, Mugenyi L, Nakiyingi L, et al. Predictors of treatment success and mortality among HIV-infected smear-negative tuberculosis patients. Int J Tuberc Lung Dis. 2015;19(6):706-713. [Google Scholar] [Crossref]

25. Biadgilign S, Reda A, Kamalkar M, et al. Predictors of tuberculosis among adults living with HIV in Ethiopia. AIDS Res Treat. 2012;2012:593781. [Google Scholar] [Crossref]

26. Mohan R, Kaliaperumal K, Dorairajan G, et al. Study of chest radiological patterns in HIV-positive patients with pulmonary TB. J Clin Diagn Res. 2015;9(12):OC05-OC07. [Google Scholar] [Crossref]

27. Kisembo HN, Bongomin F, Kirenga BJ, et al. Chest radiograph reading and recording system (CRRS): evaluating the agreement and clinical impact on the management of HIV-associated tuberculosis. Br J Radiol. 2012;85(1018):e938-e945. [Google Scholar] [Crossref]

28. Post FA, Wood R, Pillay GP, et al. Pulmonary tuberculosis in HIV infection: radiographic appearance is related to degree of immunosuppression. Clin Radiol. 1995;50(11):776-780. [Google Scholar] [Crossref]

29. Dosumu EA. West African College of Physicians dissertation. Delta State University Teaching Hospital, Nigeria; 2021. [Google Scholar] [Crossref]

30. Lawn SD, Wilkinson RJ. Immunopathogenesis of HIV-associated tuberculosis. Lancet HIV. 2015;2(8):e319-e321. [Google Scholar] [Crossref]

31. Bhaskaran K, Hamouda O, Sannes M, et al. Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA. 2008;300(1):51-59. [Google Scholar] [Crossref]

32. Harries AD, Zachariah R, Corbett EL, et al. The HIV-associated tuberculosis epidemic -- when will we act? Lancet. 2010;375(9727):1906-1919. [Google Scholar] [Crossref]

33. World Health Organization. Global tuberculosis report 2024. Geneva: WHO; 2024. [Google Scholar] [Crossref]

34. Affusim TF, Obiako RO, Ogunniyi A, et al. Correlation of CD4 lymphocyte count and chest x-ray findings in HIV patients with pulmonary tuberculosis in Ilorin, Nigeria. J Med Trop. 2013;15:22-27. [Google Scholar] [Crossref]

35. Frey A, Kilian AH, Kendagana A, et al. Chest radiography findings in HIV-positive and HIV-negative patients with pulmonary tuberculosis in rural Uganda. Medicine. 2023;102(45):e32842. [Google Scholar] [Crossref]

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