A total of 4673 patients from the Cologne/Bonn HIV cohort, enrolled between 2006 and 2017, contributed to the dataset (Fig. 1).

Outline of study design and findings regarding incidence density rate (IDR). TB tuberculosis, IDR incidence density rate (cases per 100 patient-years of observation), SD standard deviation

On average, 1830 [1616–1907] patients from this cohort had annual visits in Cologne and 1115 [1042–1148] in Bonn. Patient characteristics, demographic and clinical data are shown in Table 1.

Patients were predominantly male (3742, 80%) and of German origin (3383, 72%), i.e., born in Germany. The second most prevalent region of origin was Sub-Saharan Africa (439, 9%). In the entire cohort, median age of females at initial diagnosis of HIV was significantly lower compared to males (30.52 years vs. 35.16 years respectively, p < 0.001). The predominant HIV transmission risk group was men who have sex with men (MSM) in male patients (2434, 65%) and heterosexual contacts in female patients (436, 47%).

During the observation period, 60 (37 male, 23 female) patients were diagnosed with active TB. People from Sub-Saharan Africa accounted for a relevant group with 37% (22/60) whereas only 23% of all HIV/TB-coinfected individuals originated from Germany (Table 1). The remaining proportion (24/60, 40%) originated from other countries or regions. There was a significantly different proportion of individuals originating from other countries than Germany for coinfected women and men, with 91% (21/23) being female and 68% (25/37) being male (p = 0.035). A large part (16/23, 70%) of the female patients originated from Sub-Saharan Africa, while Germany was the main origin among male patients (12/37, 32%).

For HIV/TB-coinfected patients, the median age at time of initial HIV diagnosis was 35.1 years (IQR 28.1–39.6) whereas median age at initial TB diagnosis was 38.6 (IQR 31.9–45.4) years. In patients originating from Germany, active TB was more likely to occur in people > 38 years of age. In HIV/TB-coinfected individuals from foreign countries, TB was predominately among patients < 38 years of age (24/46, 52%).

Women were significantly younger than men at time of TB diagnosis (35.6 years [IQR 30.5–40.6], 41.2 years [IQR 34.6–48.2] respectively, p = 0.049).

Overall, 22 of the 60 coinfected patients (37%) were diagnosed concomitantly for HIV and active TB.

In the entire cohort, 87.4% (4084/4673) were treated with ART, whereas only 41.7% (25/60) of the HIV/TB-coinfected patients had received ART prior to their TB diagnosis (p < 0.001). At the beginning of the observation period, median CD4 + cell counts were significantly lower among HIV/TB-coinfected individuals compared to the non-tuberculosis group (230 cells/µl [110–420] vs. 387 cells/µl [220–570], respectively, p < 0.001). The median viral load (VL) was significantly higher (60,433 copies/ml [259–184,052] vs. 3316 [49–58,166], p < 0.001) in HIV/TB-coinfected patients (Table 1). In the 60 patients with HIV/TB coinfection, isolated pulmonary TB accounted for 35% (21/60), followed closely by disseminated TB (infection involving 2 or more non-contiguous sites) at 31.7% (19/60). Isolated lymph node tuberculosis represented the third most common entity in our cohort, comprising 16.7% (10/60) of cases (Table 2).

TB-free overall survival was 98.7% throughout the entire cohort, with significant differences regarding sex, origin, status of ART, CD4 + cell count, and viral load at observation start. Women had a lower TB-free survival compared to men, especially when ART had not been initiated before the time of TB diagnosis, with only 87.6% survival rate for women vs. 95.6% for men (p = 0.002). CD4 + cell count < 200/µl and viral load > 5 log10 copies/ml had a negative impact on TB-free survival rates (p < 0.001), particularly among patients who never started ART (Supplemental Table 1).

Patients originating from Sub-Saharan Africa showed the lowest TB-free survival rates compared to patients originating from Germany (95.0 vs. 99.6%, p < 0.001) or other countries or regions (97.2%). The TB-free survival rate for individuals originating from Sub-Saharan Africa dropped further (75.0%) if ART had not been initiated at the time of TB diagnosis (in comparison to 98.2% of German patients, p < 0.001). Patients originating from Germany, on ART, and with CD4 + cell counts ≥ 200 cells/µl had the best outcome (TB-free survival 99.9%) while lowest TB-free survival rate (16.7% survival rate; p = 0.001) was seen among patients without ART, originating from Sub-Saharan Africa and with a CD4 + cell count < 200 cells/µl. Overall, we observed that patients originating from countries with a TB incidence ≥ 10–50/100,000 and > 50/100,000 showed significantly lower TB-free survival (93.4% and 89.9%) than patients originating from countries with a TB incidence < 10/100,000 (99,1%, p < 0.001) (Fig. 2).

TB-free survival of patients with known country of origin (4263/4673, 91.2%) based on TB incidences in the countries of origin according to the 2023 WHO Global Tuberculosis Report. The incidences were divided into three groups: < 10/100,000 (n = 3396), 10–50/100,000 (n = 334), and > 50/100,000 (n = 533). In the statistical analysis (log-rank test; significance level 5%), the curves show a significant difference (p < 0.001)

Multivariable Cox regression models to identify associated risk factors for TB confirmed the Kaplan–Meier data described above. We included sex, region of origin or the origin stratified by TB incidence, respectively, as well as ART status, CD4 + cell count, and viral load at enrollment as influencing factors. The adjusted hazard ratios (HR) for the association of factors are presented in Supplemental Table 2. Patients originating from countries other than Germany, particularly Sub-Saharan African countries, or from countries with TB incidences > 10/100,000, and patients with CD4 + cell counts below 200 cells/µl were significantly more likely to develop TB. In this evaluation, a high viral load (≥ 5 log10 copies/ml) indicated a higher risk which was not statistically significant. The most influential factor was the absence of ART before the diagnosis of TB, leading to a more than tenfold increased risk for active TB. Patients on ART had the highest hazard ratio for developing TB if they originated from Sub-Saharan Africa (HR 13.42 CI [3.59–50.13], p < 0.001) or a country with a TB incidence > 50/100,00 (HR 8.04 CI [2.76–23.45], p < 0.001) (Supplemental Table 2).

To better compare our data to previously published studies, we determined IDR values. There was a total of 33,136.14 years of observation for 4673 patients. With a mean observation time of 7.09 years (± 4.27 SD), the IDR for the entire observation span was 0.181 cases per 100 patient-years of observation (CI [0.138–0.233]) (Table 3).

As expected, a significantly higher TB IDR was found for patients originating from Sub-Saharan Africa (0.694 cases per 100 patient-years of observation, CI [0.435–1.050] p = < 0.001) or from countries with a TB incidence > 10/100,000 (Table 4). Also in female patients (0.342 cases per 100 patient-years of observation, CI [0.217–0.513], p = 0.0005), patients with CD4 + cell counts < 200 cells/µl (0.444 cases per 100 patient-years of observation, CI [0.290–0.651], p < 0.001) and viral loads ≥ 5 log10 (0.428 cases per 100 patient-years of observation, CI [0.262–0.662], p < 0.001) showed significantly higher TB IDRs (Table 4).

There was an approximately 10- to 20-fold higher TB IDR among patients who did not receive ART (1.523 cases per 100 patient-years of observation, CI [1.061–2.118], p < 0.001). This ratio also remained after analysis by region and TB incidence of origin (Table 4).

TB IDR was increasing with decreasing CD4 + cell count, this trend was constantly observed in each subgroup. The highest TB IDR was found among patients who did not receive ART and patients with a CD4 + cell count below 200 cells/µl (16.850 cases per 100 patient-years of observation, CI [9.430–27.800]).

A comparison of consecutive 4-year periods during the observation time span indicated a decline in TB IDR in our cohort (Table 3). Between 2006–2009, the TB IDR ranked at 0.266 cases per 100 patient-years of observation (CI [0.177–0.385]), while it decreased non-significantly to 0.150 cases per 100 patient-years of observation (CI [0.087–0.240], p = 0.057) during 2010–2013 and further to 0.133 cases per 100 patient-years of observation (CI [0.075–0.220]) during 2014–2017(p = 0.739). Comparing the values of the earliest period with the latest, the decline was significant (p = 0.0270). This drop in IDR basically remained when stratifying by date of initial HIV diagnosis before or after 01st of January 2006. The IDRs for the aforementioned time periods were 0.158, 0.123, and 0.066 cases per 100 patient-years of observation for patients with initial HIV diagnosis before, and 0.896, 0.217, 0.240 cases per 100 patient-years of observation for patients with initial HIV diagnosis after 1st of January 2006 (Supplemental Table 3). Individuals on ART had lower IDR values than the overall cohort in all three periods and also showed the trend of decreasing IDR over time, although the proportion of individuals with a suppressed viral load at enrollment also decreased over time (Supplemental Table 3). Overall, the highest TB IDR in the entire cohort was 0.421 cases per 100 patient-years of observation in 2007.

Looking at the IDR as a function of time after the start of antiretroviral therapy, there was a significant decrease up to 7 years after the start of ART (p = 0.0001). Three years after the start of ART, the IDR had already been reduced by more than 75% compared to that of the first year (0.141 CI [0.046–0.33] vs. 0.033 CI [0.007–0.097]; p = 0.03) (Supplemental Fig. 1).