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.