Outcomes among patients with HIV-associated Tuberculosis in Guangxi,

People’s Republic of China

Zhang Yao, Yu Lan, Ma Ye, Zhao Yan, Sun Kai and Zhang Fujie

Division of Treatment and Care National Center for AIDS/STD

Chinese Center of Disease Control and Prevention

Background TB is the most common co-infection in HIV infected

population. China is a high TB burden country with a growing HIV

epidemic. HIV-associated TB – a particular problem due to its

high mortality, diagnostic challenges, and complicated simultaneous treatment of both infections – is therefore a growing concern in China.

Yet outcomes among patients with HIV associated TB in China are not well characterized.

ObjectiveThis study seeks to evaluate the magnitude

and determinants of survival among HIV infected patients with culture positive tuberculosis seeking care in the public health system in Guangxi province, China.

Design & Patients

Retrospective cohort study.Patients were identified from a cross sectional

TB screening project during 2006-2008.Adult(>18y) HIV+ patients with a positive TB

culture from any body fluid were included and followed until 12 month after TB diagnosis, or death, loss to follow-up, or transfer if earlier.

Study sites

Total population: 10 million HIV prevalence: 0.1% TB prevalence in PLWH: 20%

Treatment guidelines ART starting criteria: changed from CD4<200 to CD4<350

in 2008 ART regimen: AZT(d4T) + 3TC + EFV(NVP) Timing of ART initiation in ART-Naïve patients with active

TB: CD4<200: 2–8 weeks after TB therapy initiation CD4=200-350: after 8 weeks TB induction period CD4>350: after completion of TB therapy TB regimen: RHZE x 2months then RH x 4months,

adjusted according to drug resistance testing

Measurements Primary outcome of interest: all cause mortality

within first 12 months of TB diagnosis. Clinic records were reviewed at 12 month after the

TB diagnosis to ascertain vital status, then confirmed with national HIV database.

Socio-demographic and clinical information were extracted from patients’ charts.

Liquid culture(BacT/Alert) was used for diagnosis and TB drug resistance testing for isoniazid, rifampin, ethambutol, streptomycin.

Statistical analysis

The Kaplan–Meier method was used to estimate the probability of death after TB diagnosis.

Cox regression was used to determine risk factors associated with mortality.

Logistic regression was used to determine factors associated with receipt of TB therapy and ART.

Results-baseline characteristics (n=201)

Variable Value

Age, years, Median (IQR) 37(30-46)

Male gender, n (%) 163 (81)

Transmission Route, n(%)

Sex 102 (51)IDU 62 (31)Former plasma donor 3 (2)Unknown 34 (17)

History of TB treatment, n(%) 13 (7)

On ART at TB diagnosis, n(%) 69 (34)

Baseline CD4, median (IQR) 37 (16-101)

Extra-pulmonary TB, n(%) 111 (55)

Sources of culture samples by location, n(%)

• Sputum 168 (84)• Lymph node aspiration 39 (19)• Blood 22 (11)• Stool 11 (6)• Cerebral Spinal Fluid 7 (4)• Pleural fluid 7 (4)

Note: some patients had positive cultures from more than one sources.

Drug resistance pattern of 156 M.tuberculosis strains

TB Dug Resistance Profile

38

24

10

17 17

4

051015202530354045

AnyResistance

INHResistance

RIFResistance

EthambutolResistance

SMResistance

MDR

TB and ARV Treatment Coverage

18%

8%8%

67%

ART+ /TB Thearpy+

ART- /TB Therapy+

ART+ /TB Therapy-

ART- /TB Therapy-

(67%)

Results – 1 year clinical outcomes

Total=201Alive: 123 (61%)Dead: 47 (23%)Transferred: 17 (9%) LTFU: 14 (7%)

Accumulative Survival =75% (95%CI, 69-81%)

Risk Factors Associated with Death

* Adjusted for gender, age, mode of transmission, CD4 at study entry, extrapulmonary TB, TB drug resistance and ART status at study entry

Risk factors Univariate Multivariate*

Pvalue HR(95% CI) P value HR (95% CI)

BMI<18 0.01 2.1(1.8-3.9) 0.004 2.9(1.4-6.1)

ART during study period <0.0001 0.2(0.1-0.4) 0.001 0.3(0.1-0.6)

TB therapy during study period

<0.0001 0.2(0.1-0.3) 0.01 0.3(0.1-0.8)

Cotrimoxazole prophylaxis 0.005 0.3(0.1-0.7) 0.28 0.5(0.2-1.7)

Survival of patients by Treatment status

AHR=6; CI [3-13]

AHR=7; CI [3-18]

AHR=24; CI [9-62]

HR=1;ref

Factors associated with death or LTFU

variables Univariate Multivariate*

P value HR (95% CI) P value HR (95% CI)

BMI <18 0.007 2.1(1.2-3.5) <0.0001 3.3(1.7-6.2)

ART during study period <0.0001 0.14 (0.1-0.2) <0.0001 0.2(0.1-0.3)

TB Tx during study period <0.0001 0.2 (0.1-0.3) 0.019 0.4(0.2-0.9)

Cotrimoxazole prophylaxis <0.0001 0.3(0.1-0.5) 0.27 0.6(0.3-1.5)

* Adjusted for gender, age, mode of transmission, CD4, extrapulmonary TB, TB drug resistance, and ART status on study entry

Factors associated Receiving ARV

variables Univariate Multivariate*

P value OR (95% CI) P value OR (95% CI)

Education (above vs. below middle school)

0.033 2.0(4.0-1.1) 0.058 1.9(3.8-1.0)

Marital status (married vs. not married)

0.028 2.1 (1.1-4.1) 0.028 2.1(1.1-4.2)

Received TB Tx 0.0017 3.6 (1.6-8.1) 0.035 2.6(1.1-6.4)

* Adjusted for gender, age, BMI, mode of transmission, baseline CD4, CXR, and sputum smear

Factors associated with TB Treatment

variables Univariate Multivariate*

P value OR (95% CI) P value OR (95% CI)

CXR (typical vs. others) 0.014 4.0(1.3-12) 0.058 8.1(0.93-72)

Positive sputum smear 0.043 3.4 (1.0-11) 0.053 4.1(0.98-17)

* Adjusted for gender, age, literacy, marital status, mode of transmission, BMI, baseline CD4, EPTB and sputum smear

Conclusions and implications

This cohort of HIV+ Chinese adults with culture-positive TB demonstrated high tuberculosis drug resistance rate, high 1 year mortality and lower-than-expected treatment coverage.

These findings implicate that strengthening integrated administration of ART and TB therapies are critically important in this setting.

Acknowledgement Sponsors: Clinton Foundation, Global FundGuangxi Province Health Department: Drs. Liu Wei, Tang Zhirong,

Lu HongyanLiu Zhou CDC: Zheng Yuanjia, MDNaning 4th Hospital: Huang Shaobiao, MD University of California, San Francisco: Elvin Geng, MDUniversity of North Carolina: Zhu Hao, Ph.DNational Institute of Health: Ray Y, Chen, MD University of California, Los anginas : Wen Yi, Ph.DWorld Health Organization: Fabio Scano Washington University: Maurer Kristin