Tuberculosis, HAART Use and Survival in THRio Cohort, Rio de Janeiro, Brazil
Saraceni V1, King B2, Pacheco AG3, Golub JE2, Cavalcante SC1, Moulton LH2, Moore RD2, Chaisson RE2, Durovni B1
1-Rio de Janeiro City Health Dept., Rio de Janeiro, Brazil; 2 – Johns Hopkins SM, CTBR, Bloomberg SPH, JH HIV Clinic, Baltimore, USA; 3 – DEMQS, Fiocruz, Rio de Janeiro, Brazil
Abstract MOAB0305
Background
• Questions remain concerning the best time to initiate
HAART after TB diagnosis
• THRio – Observational cohort study to assess impact of
TB screening and INH preventive therapy on TB incidence
• Universal access to HAART in Brazil
• High TB-burden scenario – common first HIV diagnosis
and leading cause of death in HIV patients1
1. Saraceni et al., IJTLD 2008;12:769
Objectives
• Compare survival after TB diagnosis in HIV-positive
subjects followed at 29 health units in Rio de Janeiro
• Comparisons:
– exposure to HAART vs. no HAART in the overall group
– among those who initiated HAART, timing of initiation of
ARV therapy:
• Early HAART (<60 days of TB therapy)
• Deferred HAART (61-180 days of TB therapy)
• Withheld HAART (> 180 days of TB therapy)
Methods
• Inclusion Criteria:
– First episode of TB diagnosed from 01 Sep 2003 to 30
Jun 2006
– HIV diagnosed either before or after TB
– Right censored at last note in chart or 31 Dec 2006
– Mortality data available through State surveillance
system up to 31 Dec 2006
• Statistical Analysis:
– Descriptive statistics
– Kaplan-Meier estimates
– Cox proportional hazards regression models
Results
• At time of this analysis:
– 15,426 HIV+ patients receiving care in Rio City clinics
– 963 (6%) new TB cases diagnosed from 01 Sep 2003 to 30 Jun
2006
– 632 (66%) patients were HAART-naive at time of TB diagnosis
– 459 (73%) started HAART in the follow-up period
– 85/632 TB patients (13%) died during follow up
Table 1 – Characteristics of subjects by survival status
Characteristics Died(n=85)
Survived(n=547)
p-value
Gender male 67% 66% 0.847
Age (median, years) 36 36 0.329
HIV Dx after TB Dx 27% 39% 0.031
CD4 – TB (median, IQ) 164 (84-310) 183 (82-332) 0.871
VL – TB (log-median, IQ)) 4.4 4.5 0.576
TB Tx completed 32% 81% <0.001
HAART exposure (%) 49% 76% < 0.001
Table 2 – Characteristics of subjects by exposure to HAART
Characteristics HAART(n=459)
No HAART(n=173)
p-value
Gender male 68% 60% 0.049
Age (mean, years) 36 36 0.755
HIV Dx after TB Dx 38% 36% 0.531
CD4 – TB (median,IQ)) 150 (69-280) 355 (168-548) < 0.001
VL – TB (log, median) 4.4 4.4 0.639
TB Tx completed 82% 55% < 0.001
Death (#) 9% (42) 25% (43) < 0.001
Table 3 – Characteristics of subjects by timing of exposure to HAART
Characteristics <= 60 days(n=165)
61-180 days(n=168)
> 180 days(n=126)
Gender male 70% 70% 64%
Age (mean, years) 35 37 36
HIV Dx after TB Dx 24% 38% 58%
CD4 – TB (median,IQ) 135 (57-241) 137 (71-280) 202 (97-316)
VL – TB (log, median) 3.7 4.7 4.7
TB Tx completed 78% 84% 85%
Death (#) 7% (11) 11% (19) 10% (12)
Table 4 – Time to HIV diagnosis after TB episode among those exposed to HAART
Time to HIV diagnosis after TB
Median time in days IQ range P-value
<=60 days 7 4 – 31
61-180 days 27 3 – 66 0.009
> 180 days 67 24 - 196 <0.001
Graph 1 – Kaplan-Meier: Survival After a TB diagnosis, by exposure to HAART
Log-rank test – p<.001
.7.8
.91
Pro
port
ion
Sur
vivi
ng
0 500 1000 1500Time in days
No Yes
HAART ExposureSurvival after a TB diagnosis
Graph 2 – Kaplan-Meier: Survival After a TB diagnosis, by completion of TB treatment
Log-rank test – p<.001
.4.6
.81
Pro
port
ion
Sur
vivi
ng
0 500 1000 1500Time in days
No Yes
By TB treatment completionSurvival after a TB diagnosis
Graph 3 – Kaplan-Meier: Survival After a TB diagnosis, by completion of TB treatment, of those who survived longer
than 180 days
Log-rank test – p<. 001
.5.6
.7.8
.91
Pro
port
ion
Sur
vivi
ng
0 500 1000 1500Time in days
No Yes
By TB treatment completionSurvival after a TB diagnosis
Graph 4– Kaplan-Meier: Survival After a TB diagnosis, by CD4 category
Log-rank test – p=.985
.8.8
5.9
.95
1P
ropo
rtio
n S
urvi
ving
0 500 1000 1500Time in days
< 200 >= 200
By CD4 categorySurvival after a TB diagnosis
Graph 5 – Kaplan-Meier: Survival After a TB diagnosis, by timing of TB and HIV diagnosis
Log-rank test – p=.018
.7.8
.91
Pro
port
ion
Sur
vivi
ng
0 500 1000 1500Time in days
HIV after TB HIV before TB
By HIV and TB diagnosisSurvival after a TB diagnosis
Graph 6 – Kaplan-Meier: Time to HAART: <=60, 61-180 or > 180 days after TB treatment started
Log-rank test – p=.306
.8.8
5.9
.95
1P
ropo
rtio
n S
urvi
ving
0 500 1000 1500Time in days
<= 60 d 61 - 180 d> 180 d
By timing to HAARTSurvival after a TB diagnosis
Table 5: Cox model – Univariate analysis, all cases
Covariates HR CI 95% p-value
Gender 0.97 0.61 – 1.52 0.882
Age (years) 1.00 0,98 – 1.03 0.765
CD4 (absolute) 1.00 0.99 – 1.00 0.717
CD4<200 0.96 0.52 – 1.77 0.895
Viral load (log) 1.22 0.99 – 1.52 0.068
HIV before TB 1.79 1.09 - 2.91 0.020
HAART exposure 0.30 0.20 – 0.47 <0.001
TB Tx completed 0.12 0.07 – 0.19 <0.001
Table 6: Final Cox model, all cases
Covariates aHR CI 95% p-value
HAART (Yes) 0.48 0.31 – 0.74 0.001
TB Tx completed 0.14 0.09 – 0.22 <0.001
Conclusions
• HAART exposure significantly related to improved
survival after TB diagnosis (univariate HR=0.30;
aHR=0.48)
• The benefits of HAART were found despite lower median
CD4 counts in those who received it vs. those who did not
• Time of initiation of HAART not associated with
significant changes in survival
• Delays in diagnosis HIV in TB patients associated with
lower likelihood of receiving HAART
– Universal opt-out testing for all TB patients essential
