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.

Objective  This 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  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= : 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) VariableValue 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 and ARV Treatment Coverage (67%)

Results – 1 year clinical outcomes Total=201 Alive: 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 UnivariateMultivariate* PvalueHR(95% CI)P valueHR (95% CI) BMI< ( ) ( ) ART during study period < ( ) ( ) TB therapy during study period < ( ) ( ) Cotrimoxazole prophylaxis ( ) ( )

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 UnivariateMultivariate* P valueHR (95% CI)P valueHR (95% CI) BMI < ( )< ( ) ART during study period < ( )< ( ) TB Tx during study period < ( ) ( ) Cotrimoxazole prophylaxis < ( ) ( ) * Adjusted for gender, age, mode of transmission, CD4, extrapulmonary TB, TB drug resistance, and ART status on study entry

Factors associated Receiving ARV variables UnivariateMultivariate* P valueOR (95% CI)P valueOR (95% CI) Education (above vs. below middle school) ( ) ( ) Marital status (married vs. not married) ( ) ( ) Received TB Tx ( ) ( ) * Adjusted for gender, age, BMI, mode of transmission, baseline CD4, CXR, and sputum smear

Factors associated with TB Treatment variables UnivariateMultivariate* P valueOR (95% CI)P valueOR (95% CI) CXR (typical vs. others) (1.3-12) ( ) Positive sputum smear (1.0-11) ( ) * 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 Fund Guangxi Province Health Department: Drs. Liu Wei, Tang Zhirong, Lu Hongyan Liu Zhou CDC: Zheng Yuanjia, MD Naning 4 th Hospital: Huang Shaobiao, MD University of California, San Francisco: Elvin Geng, MD University of North Carolina: Zhu Hao, Ph.D National Institute of Health: Ray Y, Chen, MD University of California, Los anginas : Wen Yi, Ph.D World Health Organization: Fabio Scano Washington University: Maurer Kristin