Tuberculosis among people living with HIV/AIDS in the German ClinSurv HIV Cohort: long-term incidence and risk factors

Abstract

Background: Tuberculosis (TB) still presents a leading cause of morbidity and mortality among people living with HIV/AIDS (PLWHA), including those on antiretroviral therapy. In this study, we aimed to determine the long-term incidence density rate (IDR) of TB and risk factors among PLWHA in relation to combination antiretroviral therapy (cART)-status.

Methods: Data of PLWHA enrolled from 2001 through 2011 in the German ClinSurv HIV Cohort were investigated using survival analysis and Cox regression.

Results: TB was diagnosed in 233/11,693 PLWHA either at enrollment (N = 62) or during follow-up (N = 171). The TB IDR during follow-up was 0.37 cases per 100 person-years (PY) overall [95% CI, 0.32-0.43], and was higher among patients who never started cART and among patients originating from Sub-Saharan Africa (1.23 and 1.20 per 100PY, respectively). In two multivariable analyses, both patients (I) who never started cART and (II) those on cART shared the same risk factors for TB, namely: originating from Sub-Saharan Africa compared to Germany (I, hazard ratio (HR); [95% CI]) 4.05; [1.87-8.78] and II, HR 5.15 [2.76-9.60], CD4+ cell count <200 cells/μl (I, HR 8.22 [4.36-15.51] and II, HR 1.90 [1.14-3.15]) and viral load >5 log10 copies/ml (I, HR 2.51 [1.33-4.75] and II, HR 1.77 [1.11-2.82]). Gender, age or HIV-transmission risk group were not independently associated with TB.

Conclusion: In the German ClinSurv HIV cohort, patients originating from Sub-Saharan Africa, with low CD4+ cell count or high viral load at enrollment were at increased risk of TB even after cART initiation. As patients might be latently infected with Mycobacterium tuberculosis complex, early screening for latent TB infection and implementing isoniazid preventive therapy in line with available recommendations is crucial.

Figure 1

Overview on the patients included in the study and their characteristics at enrollment in the ClinSurv HIV Cohort, Germany 2001–2011. TB, tuberculosis; MSM, men who have sex with men; IQR, interquartile range.

Figure 2

The trend of tuberculosis incidence density rate during follow-up, among (a) patients who never started cART (N = 59) and (b) patients on cART (N = 111) in the ClinSurv HIV Cohort, Germany 2001–2011. A low number of patients who never started cART remained under observation beyond 4 years of follow-up, where no TB cases reported in the 5th, 7th, 8th, 9th and 10th years of follow-up. P < 0.001 for trend for TB incidence in patients who never started cART and patients on cART.

Figure 3

Kaplan-Meier plots of tuberculosis (TB)-free survival proportion in the ClinSurv HIV Cohort, Germany 2001–2011. (a) among all patients; (b) among all patients stratified by combination antiretroviral therapy (cART)-status; (c) among all patients stratified by region of region; (d) among all patients stratified by CD4+ cell count; (e) among patients who never started cART stratified by region of origin; (f) among patients who never started cART stratified by CD4+ cell count; (g) among patients on cART stratified by region of origin; (h) among patients on cART stratified by CD4+ cell count. Observation period for patients who never started cART began at enrollment, while for patients on cART began at the time of cART initiation.