1. Tuberculosis incidence and risk factors among adult patients receiving HAART in Senegal: a 7-year cohort study Assane DIOUF et al. IRD/UMR 145 CRCF, CHNU de Fann XVI International AIDS Conference, Toronto, Canada, 14 August 2006

2. BACKGROUND (1) TB in Senegal (WHO 2004): –incidence: 2.45 cases/1000 person-yrs –mortality: 52 cases/100000 p-y TB and HIV infection: –first opportunistic infection (OI); –difficulties in diagnosis and treatment; –HIV prevalence = 15% among TB patients

3. BACKGROUND (2) TB among adult patients receiving HAART: –most frequent OI –leading cause of death (18%) –incidence?

4. OBJECTIVES Assessment of HAART efficacy 7 years and half after initiation Determine incidence and risk factors of tuberculosis ANRS 1290 COHORT Inclusion period: August 1998 - April 2002 N = 403

5. FOLLOW-UP VISITS Pre-enrolment and enrollment visits: clinical, biology, CD4 counts, viral load M1 : clinical, viral load (VL), adherence Bi-monthly visits: clinical, adherence, serious adverse events (SAE) Six-monthly visits: clinical, adherence, SAE, standard biology, CD4 counts, VL

6. MONITORING AT MARCH 31, 2006 Participation time – median: 52 months – range: 0.6 – 90 months Deaths: 95 Lost to follow-up –1st year: 7 –2d year: 8 –3d year: 7 1543 p-y at risk as of March 31, 2006

7. BASELINE CHARACTERISTICS (1) Characteristicn (%) Median age (IQR) < 45 years 37 years (31 – 43) 308 (76.8%) Sex ratio M:F1:1.2 Clinical stage - CDC C224 (55.5%) Median Body mass index (IQR) < 19 kg.m -2 19.8 (17.9 – 22.4) 151 (38.6%) ART naïve History of tuberculosis Antituberculosis drugs 362 (94.5%) 114 (28.2%) 47 (11.6%) Cotrimoxazole prophylaxis317 (78.5%)

8. BASELINE CHARACTERISTICS (2) Characteristicn (%) PI containing regimen169 (41.8%) Median haemoglobin level (IQR) < 10 g/dL 10.7 (9.5 – 12.0) 136 (34%) Median total lymphocytes count (IQR) < 1200 cells/μL 1443 (1042 – 2008) 144 (36.7%) CD4 cells/μL Median (IQR) < 50 50 - 199 ≥ 200 128 (54 – 217) 96 (24.3%) 177 (44.8%) 122 (30.9%) Median HIV-1 viral load log cp/mL (IQR) ≥ 5log 5.2 (4.7 - 5.6) 203 (61.5%)

9. UNDETECTABLE VIRAL LOAD

10. CHANGE IN CD4 COUNTS

11. CUMULATIVE PROBABILITY OF DYING

12. SURVIVAL PREDICTORS Predictor * Adjusted mortality ratio (95% CI) Clinical stage A/Bns BMI ≥ 19 kg.m -2 0.54 (0.35 – 0.82) Haemoglobin level ≥ 10g/dL 0.56 (0.37– 0.85) CD4 ≥ 200 cells/μL0.43 (0.24 – 0.77) Lymphocytes ≥ 1200 cells/μL ns

13. TB INCIDENT CASES N = 47 30 incident cases declared as an adverse event during follow-up: –23 alive as of March 31, 2006 –7 dead from non-TB cause 17 deaths due to TB which was not previously recorded Overall incidence rate:3.1/100 p-y

14. CUMULATIVE TB INCIDENCE

15. TB HAZARD RATE

16. BASELINE PREDICTORS OF TB PredictorLog rank History of TB0.26 Age < 45 years0.46 BMI < 19 kg.m20.13 Haemoglobin level < 10 g/dL0.01 CD4 counts < 50 cells/µL0.05 Viral load > 5 log0.23

17. PREVIOUS FINDINGS (1) Seyler C: Ivory coast, 7 yrs cohort study –4.8/100 p-y –Risk factors: history of tuberculosis (11.3 vs 3/100 p-y) Lawn SD: South africa, 5 yrs follow up –3.5/100 p-y in the 1 st yr; 1/100 in the 5 th yr –Risk factors associated: CD4 cells < 100/µL;WHO stage 3 or 4; age < 33 yrs

18. PREVIOUS FINDINGS (2) Girardi: Europa and North America, three yrs –4.69/1000 p-y (D0-M36); –3.1/1000 p-y (M6-M36) –Risk factors: low CD4 count at D0 and at M6; VL > 400/mL at M6

19. CONCLUSIONS Good immunological and virological efficacy Short term mortality after HAART initiation remains high Early occurrence of TB (first year) Role of IRIS? Benefits of INH preventive therapy? Necessity of early tracking of HIV Necessity of collaboration between AIDS TB programs

20. CHNU Fann, Centre Régional de Recherche Clinique et de Formation sur le VIH/sida, Dakar, Sénégal –Diouf A –Dieng AB CHNU Fann, Clinique des Maladies Infectieuses, Dakar, Sénégal : –Sow PS –Ndiaye I CHNU Fann, Centre de Traitement Ambulatoire, Dakar, Sénégal: –Ngom Guèye NF Hôpital Principal de Dakar: –Guèye PM –Ba Fall K ANRS 1290 STUDY GROUP Conseil National de Lutte contre le Sida, Dakar, Sénégal : – Cilote V –Lanièce I –Ndoye I Institut de Recherche pour le Développement, UMR 145, Montpellier, France: –Etard JF –Delaporte E – Laurent C –Thierry-Mieg M