Incidence of tuberculosis in the first year of antiretroviral treatment in West-African HIV-infected adults B. Tchakounte Youngui1, P. Coffie2, E. Messou3, A. Poda4, L. Fortes Déguénonvo5, D. Hawerlander6, A. Minga7, E. Balestre8, F. Dabis9, O. Marcy9 (1) ISPED, University of Bordeaux, France, (2) Programme PACCI, Site ANRS, Abidjan, Côte D'Ivoire, (3) CePReF-Aconda-VS, Abidjan, Côte D'Ivoire, (4) CHU Souro Sanou, Bobo-Dioulasso, Burkina Faso, (5) CHNU Fann, Dakar, Senegal, (6) CIRBA, Abidjan, Côte D'Ivoire, (7) CNTS/PRIMO-CI, Abidjan, Côte D'Ivoire, (8) INSERM U897, ISPED, University of Bordeaux, France, (9) INSERM U1219, University of Bordeaux, France Paris July 24th 2017

“No conflicts of interest to declare”. Conflict of Interest “No conflicts of interest to declare”.

Background HIV prevalence |2015 TB burden in PLHIV |2015 36.7 million worlwide / 25.5 million (69.9%) in Sub-Saharan Africa TB burden in PLHIV |2015 1.17 million cases worlwide /834,000 (71.3%) in Africa 390,000 deaths worlwide/ 300,000 (76.9%) in Africa TB incidence in PLHIV Improved access to antiretroviral therapy (ART) ⇒ reduction of TB incidence remains higher in PLHIV on ART than in non-infected persons TB prevention in PLHIV Isoniazid preventive therapy (IPT) recommended, not implemented in West Africa UNAIDS Data, WHO Global TB report 2016, Duda et al 2010 (IeDEA)

Background and Objective Assess tuberculosis incidence during the first year of antiretroviral therapy and identify associated factors in HIV- infected adults in West Africa

Methods: Study design and population IeDEA West African collaboration cohort 3 HIV outpatient centers in Côte d'Ivoire (Abidjan), Burkina Faso (Bobo Dioulasso), and Senegal (Dakar) Inclusion criteria HIV-infected adults (≥16 years) initiating ART between 2010 and 2014 Without ongoing TB at ART initiation ≥1 follow-up visit Patient follow-up Usual site visit calendars No IPT

Methods: Study design and population TB diagnosis Systematic symptom screening for active TB According to national recommendations Sputum microscopy and chest radiography Xpert perfom if smear negative (since 2013) Endpoint: incident TB defined as first TB event notified > 1 week and ≤ 1 year on ART Statistics: Crude incidence Adjusted incidence and associated factors identified by multivariate Poisson regression models

3,213 included in our analysis Results 4,154 started ART since 2010 in the 3 sites 3,404 on ART with ≥ 1 follow-up visit 750 without follow-up visit after ART initiation 3,213 included in our analysis 191 patients with ongoing TB at initiation of ART. 170 incident TB cases

Results – Patients characteristics   N n or median % or IQR Country 3213 Côte d’Ivoire (CI) 959 29.8 Burkina Faso (BF) 1863 58.0 Senegal (SN) 391 12.2 Age (years) 3192 38.5 32.0 – 45.4 Sex female 3210 2153 67.1 BMI (kg/m2) 3064 20.6 18.0 – 24.0 Past TB history 2559 176 6.9 CD4 cell count (cells/µl) 3067 211 95 – 343 Hemoglobin level (g/dl) 3063 11.0 9.4 – 12.2

Results - TB incidence density rate   Period at risk (years), median (IQR) No. at risk PY at risk TB cases Crude incidence rate /100 PY (95%CI) CI 1.00 (0.51 – 1.00) 959 744.7 106 14.23 (11.52–16.94) BF 1.00 (0.37 – 1.00) 1863 1334.0 59 4.42 (3.29–5.55) SN 0.99 (0.46 – 1.00) 391 281.8 5 1.77 (0.22–3.33) ALL 1.00 (0.44 – 1.00) 3213 2360.5 170 7.2 (6.12–8.28)

Results - TB incidence and associated factors Now looking at associated factors with incidence of TB in adjusted model. The country, sex, BMI, past history of TB, CD4 count and hemoglobin was significally associated with occurrence of TB in PLHIV As we can see in penultimate column, the risk of TB was more high in patient living in Côte d’Ivoire than patient living in Burkina Faso and Senegal. Male patients had almost 2 times more risk than female, patient with a past history of TB had 4 times more risk than patient without past TB history and patients with hemoglobin less than nine had almost 2 times more risk than patient with hemoglobin at least eleven Finally, we highlight here adjusted incidence rate of tuberculosis in the first year of ART after controlling baseline characteristics, corresponding to the incidence of tuberculosis in a female patient from Burkina Faso, with a normal BMI, CD4 count greater than 500 and hemoglobin greater than eleven. It was one point forty two case per one hundred patients at risk which corresponds to one thousand forty hundred and twenty cases per one hundred thousand patients at risk if we convert according to the usual unit used by the World Health Organisation

Discussion Overall TB incidence rate is 20 times higher than the incidence of TB in the general population of the 3 countries. Associated factors: sex, CD4, Hb level, past history of TB strongly associated with the incidence of TB on ART: similar result found by Seyler et al. In 2005 in Abidjan. Adjusted incidence 4 times higher in patients from CI in line with incidence rates in the general population: BF: 54 [48 – 59] cases / 100,000 PY CI: 165 [150 – 179] cases / 100,000 PY SN: 138 [122 – 154] cases / 100,000 PY

Conclusion Tuberculosis incidence remains high during the first year on ART in the West African context in the absence of IPT Several studies demonstrate the efficacity of combining ART and IPT in reducing of tuberculosis incidence and mortality in PLHIV Implementation of IPT is necessary in PLHIV in West African settings despite lower incidence rates in the general population compared to Eastern or Southern Africa Temprano Anrs Study Group, 2015

IeDEA West Africa participating sites: Acknowledgments All the team of IeDEA West Africa Regional Office (PAC-CI, Abidjan, Côte d’Ivoire) IeDEA West Africa participating sites: Burkina Faso , Bobo Dioulasso: Jacques Zoungrana, Ibrahim Soré, Achille Tapsoba (CHU Souro Sanou) Côte d’Ivoire, Abidjan: Henri Chenal, Magloire Moh (CIRBA), Joachim Charles Gnokoro, Koffi Ladji Issouf (ACONDA-CePReF), Yao Abo, Jean Michel Yoboue (CMSDS/CNTS) Senegal, Dakar: Moussa Seydi, Judicael Malick Tine(SMIT, CHU Fann)

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