1. THE 6 TH NATIONAL SCIENTIFIC CONFERENCE ON HIV/AIDS Yield and impact of repeated screening for tuberculosis and isoniazid preventive therapy among patients with HIV in Vietnam Duong BD 1, Thai LH 2, Cowger T 2, Nhung NV 3, Nhan DT 1, Thoa CK 1, Khanh VT 4, Thinh T 5, Dung NH 6, Yen NTB 6, Ngoc DV 5, McConnell M 2, Whitehead S 2, Pevzner ES 2. Presenter: Duong BD 1 Vietnam Authority for HIV/AIDS Control; 2 U.S. Centers for Disease Control and Prevention; 3 National Lung Hospital; 4 VAAC-U.S. CDC Cooperative-agreement Project; 5 Ho Chi Minh City Provincial AIDS Committee; 6 Pham Ngoc Thach Hospital.

2. The 6 th National Scientific Conference on HIV/AIDS Background  Tuberculosis leading infection and cause of death in people living with HIV (PLHIV)  Diagnosis challenging  Previously, no evidence-based algorithm to screen/diagnose TB in PLHIV  2007: CDC with Vietnam, Cambodia, Thai HIV and TB programs conducted ID-TB/HIV study to identify algorithm to screen for, diagnose and rule out TB  Identified algorithm screens for 3 symptoms: 1) cough of any duration; 2) fever of any duration; 3) night sweats >3 weeks  2010- 2011: CDC and Vietnam HIV-TB programs conducted study to evaluate algorithm in programmatic conditions

3. The 6 th National Scientific Conference on HIV/AIDS Study objectives To evaluate  the diagnostic yield of screening for TB and using the diagnostic algorithm at baseline  the diagnostic yield of TB screening and diagnosis algorithm during follow-up  the outcomes of PLHIV screening negative and starting IPT  the impact of ART and IPT on risk for TB among PLHIV during follow-up  the impact of routine screening for TB using the algorithm on mortality among PLHIV

4. The 6 th National Scientific Conference on HIV/AIDS Methods: Study sites and subjects  One-year longitudinal cohort study  Study sites: 3 HIV outpatient clinics (OPC) in Hanoi and HCMC  Subjects  Eligible: HIV+ patients aged >15 years and not yet receiving ART  At each clinical encounter screened using TB algorithm  Ineligible for follow-up if diagnosed with TB or currently receiving anti-TB treatment

5. The 6 th National Scientific Conference on HIV/AIDS Methods: Data collection  At enrollment: ‒ Eligibility and demographic data ‒ Physical exam findings ‒ Medical history ‒ TB-related medications ‒ Date and screening results  At each clinical encounter: ‒ Date and screening results ‒ Deviations from the diagnostic algorithm ‒ Dates of ART and/or IPT initiation ‒ CD4 values ‒ Dates of death, LTFU, TB diagnosis

6. The 6 th National Scientific Conference on HIV/AIDS Data analysis Bivariable and multivariable analysis of relationships between predictors and screening results during follow-up Time-to-event analyses of incident TB and death

7. The 6 th National Scientific Conference on HIV/AIDS Yield of Repeated TB Screenings

8. The 6 th National Scientific Conference on HIV/AIDS Yield of Repeated TB Screenings

9. The 6 th National Scientific Conference on HIV/AIDS Incidence of TB at enrollment and follow-up screenings *An additional 16 cases of TB diagnosed at non-study sites during follow-up 1-year period prevalence was 12,421 per 100,000 persons *

10. The 6 th National Scientific Conference on HIV/AIDS Time to incident TB Time to TB: Median: 88 days IQR: 64-142 days 29 Cases of incident TB Incidence: 4,966 per 100,000

11. The 6 th National Scientific Conference on HIV/AIDS ART and IPT initiation during follow-up At 1 year, 85% of participants were on ART and/or IPT & 33% were on both ART and IPT

12. The 6 th National Scientific Conference on HIV/AIDS IPT and TB Risk aHR: 7.7 (2.0, 33.3) Not on IPT On IPT aHR: adjusted hazard ratio. HR adjusted for gender, age, baseline BMI, CD4 count at enrollment, ART, previous TB, smoking

13. The 6 th National Scientific Conference on HIV/AIDS ART and TB risk ART 3 months aHR: 16.9 (4.2, 68.2) ART <3 months No ART No ART v. ART >3 months aHR: 12.1 (2.5, 59.0) ART >3 months

14. The 6 th National Scientific Conference on HIV/AIDS Impact of regular TB screening on mortality Regular follow-up screenings <120 days: aHR: 1.56 (0.34, 7.1) Regular follow-up screenings >120 days: aHR: 10.0 (2.5, 100) aHR: adjusted hazard ratio. Hazard ratio adjusted for gender, age, baseline BMI, CD4 count at enrollment, ART, Injection drug use, and smoking

15. The 6 th National Scientific Conference on HIV/AIDS Main findings Diagnosing TB  High incidence of TB observed at enrollment and follow-up  Declining proportion of persons screening TB positive  Declining proportion of persons diagnosed with TB Preventing TB  High uptake of ART and IPT among participants  Lower TB incidence among participants prescribed IPT  Higher TB incidence among participants not on ART or <3 months ART Program impact  Lower mortality among PLHIV screened regularly for TB

16. The 6 th National Scientific Conference on HIV/AIDS Limitations Observational data - participants not randomized to receive repeated screenings No external comparison group Small number of events (TB & death) limited ability to statistically assess more complicated models. Couldn’t assess the joint effect of ART & IPT Purposeful selection of study sites so conclusions may not be generalizable to other sites in Viet Nam Gold standard diagnostic results not available for all participants so could not calculate sensitivity and specificity

17. The 6 th National Scientific Conference on HIV/AIDS Conclusions Benefits of Repeated Screening  Opportunities for initiation of ART and IPT  Additional opportunities to diagnose TB for PLHIV with missed or incomplete diagnostic evaluations  Treatment or referral for other health services

18. The 6 th National Scientific Conference on HIV/AIDS Recommendations Routine screening for TB in every visit, using TB screening and diagnosis algorithm in line with national guidelines Facilitating PLHIV’s access to new TB diagnostics such as Xpert MTB/RIF

19. The 6 th National Scientific Conference on HIV/AIDS Acknowledgements CDC (Atlanta and Vietnam) VAAC National Lung Hospital /National TB Program Hanoi PAC HCMC PAC Pham Ngoc Thach Hospital Participating OPCs

20. The 6 th National Scientific Conference on HIV/AIDS Thank you !