Multi-variable analysis
All the eight variables with a P-value <0.25 in the bi-variable conditional logistic regression were analyzed using a multivariable conditional logistic regression model to identify the independent determinants of tuberculosis infection among HIVpositives while enrolled on HAART. Among all these variables, a statistically significant association was found between length of stay in ART and tuberculosis infection. Accordingly, HIV -positive individuals who were taking anti-retroviral drugs less than 12 months had about six times the odds to develop tuberculosis infection compared to those taking ART drugs for more than 36 months (aOR=5.925, 95%CI=2.649-13.250) (Table 4).
Discussion
In this study, we assessed the demographic, behavioral, and baseline clinical determinants of tuberculosis infection amongHIV -positive individuals during their ART follow-up. From our previous retrospective cohort study, we performed a nested case-control study where the cases and controls were pair-matched exactly in age and sex. The main objective was to assess the effect of long-term ART on decreasing the incidence of tuberculosis infection. Accordingly, the finding supports our hypothesis, such that long-term exposure to ART significantly decreases the incidence of TB among HIV patients during their follow-up.
In our previous retrospective study (13), we were able to assess and compare the incidence of tuberculosis infection among HIVpatients who were taking ART with those who did not take ART. The findings showed that taking ART significantly decreases the incidence of tuberculosis (10). However, still, a considerable proportion (12.8%, 61) of HIV -positive individuals was infected with TB after ART initiation.
Based on the chi-squared test, TB co-infection among HIV patients after HAART initiation was associated with previous TB history, baseline functional status, baseline WHO clinical stage, baseline Hgb value, baseline BMI, IPT intake, baseline CD4 value, and duration of taking ART. In support of the present study finding, the association of TB infection with previous TB infection history was reported previously (26, 27). The recurrence of TB among the previously treated HIV -positive individuals might be due to the reinfection in a high TB setting like the current study setting (28). Being on the advanced clinical stages such as WHO stage III/IV, lower CD4 count (<200 cells/µl), undernutrition (BMI<18.5 Kg/m2), and bedridden functional status at the time of ART enrollment to ART was repeatedly reported to be associated with TB infection among HIV patients(10, 16, 29-31). The advanced clinical stages might be occurred due to the late diagnosis or late healthcare-seeking behavior of study participants (32, 33). These advanced clinical stages at the baseline might lead HIV patients susceptible to subsequent infections including tuberculosis. The other associated factor with TB in the current study is IPT intake status. As reported in previous studies, not taking the complete IPT prophylaxis is a risk factor for TB infection in HIV patients (16, 30, 31, 34). WHO recommends HIV positive individuals take a complete dose of IPT, such that a dose of 300mg isoniazid per day for six months (35).
To look at the strength of association and to identify the independent determinants of TB co-infection among HIV patients during their ART follow-up period, we performed both bi-variable and multi-variable conditional logistic regression analysis. Based on the multivariable analysis, long-term exposure to ART decreases the odds of tuberculosis infection in HIV -positive individuals (36), and the reverse is true. Those HIV positives who took ART for less than 12 months had about six times the odds to be infected with TB compared to those taken for more than 36 months. In support of this study, a higher incidence of TB in the early phase of HAART initiation is reported previously in different settings (37). This higher TB incidence in this stage might have several explanations. First, the advanced clinical stages such as low level of CD4 count at the time of ART initiation might be one factor. Secondly, TB-associated immune-inflammatory immune response (IRIS) might be the other factor (38). To the end, this study has important limitations, including the small sample size and the nature of the retrospective data as it was extracted from patient registries. Besides, the incomplete records were excluded due to the absence of baseline data in the original retrospective cohort study, where we selected cases and controls that might introduce selection bias.
Conclusion
A considerable proportion of individuals were infected with tuberculosis after the initiation of HAART. Baseline immunological and clinical profiles such as WHO stage III/IV, anemia, undernutrition, lower CD4 count and bedridden and ambulatory functional status, previous TB history, and not taking IPT were associated with TB infection. Most of the TB cases occurred among patients who were taking ART for less than a year and the independent determinant of TB infection was the length of stay on HAART. However, the long duration of ART exposure significantly decreases tuberculosis incidence. Screening, HIV- positive patients for tuberculosis throughout their ART follow-up would be important.