Baseline socio demographic characteristics of study participants
Out of all patients enrolled to the ART clinic from January 1, 2014 to December 31, 2018, a total of 536 charts were selected and reviewed based on the inclusion criteria. From those reviewed charts, 494 were included in the analysis and the remaining 42 (7.84%) charts were excluded due to data incompleteness.
From 494 charts included in the analysis, around 303(61.3%) were females and about 200(40.5%) from the total subjects were in the age group of 25 to 34 years. The median age for this cohort was 33 years (IQR: 27 – 40 years). Almost all of the patients 472 (95.6%) were orthodox Christian and 171 (34.6%) of the total patients had no formal education. More than three forth 377 (76.3%) were urban dwellers and 228 (46.2%) of the participants were living with the family number of 3 - 4 members. A total of 457 (92.5%) patients had disclosed their HIV status. Of these 228 (46.15%) disclosed their status to their wife or husband.
Incidence of Tuberculosis
All study participants were followed for different follow up periods for five years which gave a total of 1000.22 person year observations. Study subjects were followed for a minimum of 0.93 month and a maximum of 59.43 months. The median follow up period was 21.77 months (IQR: 7.27 – 37.7). During the total follow up period, 62 new TB case were observed which yielded a proportion of 12.55% (95% CI: 9.89, 15.79) and an overall incidence density rate of 6.19 cases per 100 person year (95% CI: 4.83, 7.95).
Among the incident TB cases diagnosed within the five years follow up period, 29 were males and 33 were females. From all new TB cases during the follow up, 25 subjects (40.3%) were within the age group of 35–44 years. Twenty four (38.7%) of new TB cases had no any formal education and most (82.3%) of TB cases were from a family size of three or more individuals (Table 1).
Baseline and follow up clinical and immunological characteristics of study participants
Out of the total 494 study participants with complete information for analysis, majority (97.17%) of them had not TB treatment history. A total of 219 (44.3%) patients were in baseline WHO clinical stages I. Only 38 (7.7%) of all patients had baseline CD4 count of less than 50 and majority were found in a group with CD4 count ≥ 350 cells/µl. The median base line CD4 count was 314.5 cells/µl (IQR: 147 - 443). Three hundred fifty nine patients (72.7%) were in the baseline hemoglobin level of ≥ 10 g/dl and the median hemoglobin level was 13.2 g/dl (IQR: 11.3 – 14.5).
Almost two third (67.4%) of participants were having a baseline body mass index of ≥ 18.5 kg/m2 with median BMI of 20.58 kg/m2 (IQR: 18.29 – 23.01). A total of 392 (79.4%) patients were enrolled to chronic HIV care clinic with working functional status. Only 79 (16%) patients had past opportunistic infections and from these only 13 patients (2.6%) had history of TB. Majority of patients, 467 (94.5%) were on TDF-3TC–EFV ART regimen at the baseline and only 16 (3.2%) of the participants were changed their regimen during follow up. Of those who have changed their initial regimen during follow up more than half (56.3%) were due to treatment failure. From all patients, 127 (25.7%) had fair or poor ART adherence level during follow up and 299 patients (60.5%) did not take IPT. More than one third (36.4%) of patients were followed for about 1 – 3 years.
From sixty two incident TB cases, TB were observed higher on patients with base line WHO clinical stage III (14.06 cases per 100 PY; 95% CI: 10.18, 19.40) and stage IV (26.37 cases per 100 PY; 95% CI: 14.97, 46.43). It was also observed that, TB incidence was noticeable among patients with baseline CD4 count of < 50 cells/µl (18.77 cases per 100 PY; 95% CI: 11.31, 31.13) and being from 50 – 100 cells/µl (18.93 cases per 100 PY; 95% CI: 11.93, 30.04). Patients with baseline hemoglobin < 10 g/dl was higher incidence, 20.17 cases per 100 PY (95% CI: 15.37 - 26.47). Of new TB cases, three fourth of cases had a BMI < 18.5 kg/m2 having an incidence 16.32 cases per 100 PY (95% CI: 12.26 - 21.72).
Forty seven patients having baseline ambulatory or bedridden functional status developed TB during follow up with an incidence of 28.00 cases per 100 PY (95% CI: 21.04, 37.27). From those new TB patients during the follow up, 47 cases were fair or poor ART adherence contributed for an incidence rate of 19.89 cases per 100 PY (95% CI: 14.95, 26.48). An incidence of 9.61 cases per 100 PY (95% CI: 7.41, 12.45) was observed on those patients who did not take IPT during follow up period. The highest incidence of TB was seen within the first year of follow up (58.13 cases per 100 PY; 95% CI: 43.11 - 78.37) (Table 2).
Kaplan-Meier plot for TB-free survival probability among adults on ART
TB-free survival probability for the total cohort at the end of six month was 0.93 (95%CI; 0.90, 0.95); at the end of twelve month was 0.90 (95%CI; 0.87, 0.93); at the end of Two years was 0.88 (95%CI; 0.85, 0.91); at the end of three year was 0.86 (95%CI; 0.82, 0.89); at the end of four year was 0.83 (95%CI; 0.78, 0.88); and that of surviving TB free at the end of follow up was 0.66 (95%CI; 0.41, 0.83) (Figure 1).
Log rank test of equality of survival for baseline Hemoglobin level, Functional status, ART adherence level and IPT usage were significantly associated with TB incidence rate of people living with HIV. Patients whose baseline hemoglobin level less than 10g/dl had a significantly lower TB-free survival probability compared to those with hemoglobin ≥ 10g/dl. Those patients who had baseline functional status of working, used IPT during follow up and had good ART adherence had significantly higher TB free survival probability than those patients with ambulatory or bedridden functional status, didn’t use IPT and had fair or poor ART adherence level respectively (Figure 2).
Predictors of Tuberculosis occurrence
In the bivariable Cox regression analysis, past TB treatment history, baseline CD4 count, WHO clinical stage at baseline, baseline haemoglobin level, baseline BMI, functional status at baseline, HIV disclosure status, ART adherence during follow up, and IPT use were found to be predictors of the incidence of TB among PLHIV at a P-value of less than 0.2. These variables were also checked for Cox proportional hazard assumption and they didn’t violate the assumption. So, they were selected for multivariable Cox-regression analysis. From these, baseline haemoglobin level, functional status at enrolment, IPT use and ART adherence level were found to be statistically significant predictors of TB incidence rate among adults on ART at a P - value of less than 0.05 (Table 3).