CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

725 THE IMPACT OF HIV-COINFECTION ON THE EVOLUTION OF MYCOBACTERIUM TUBERCULOSIS

Chloé Loiseau 1 , Marie Ballif 2 , Daniela Brites 1 , Lukas Fenner 2 , Miriam Reinhard 1 , Alash’le Abimiku 3 , Marcel Yotebieng 4 , Helen Cox 5 , E. Jane Carter 6 , Joachim Gnokoro 7 , Jimena Collantes 8 , Anchalee Avihingsanon 9 , Nicola M. Zetola 10 , Matthias Egger 2 , Sebastien Gagneux 1 1 Swiss Tropical and Public Health Institute, Basel, Switzerland, 2 Institute of Social and Preventive Medicine, Bern, Switzerland, 3 Institute of Human Virology Nigeria, Abuja, Nigeria, 4 The Ohio State University, Columbus, OH, USA, 5 University of Cape Town, Cape Town, South Africa, 6 Moi University, Eldoret, Kenya, 7 Centre de Prise en Charge de Recherche et de Formation, Dakar-Fann, Senegal, 8 Instituto de Medicina Tropical Alexander von Humboldt, Lima, Peru, 9 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 10 Botswana–UPenn Partnership, Gaborone, Botswana Background: HIV is fuelling the resurgence of human tuberculosis (TB) in many parts of the world. Adequate T-cell responses, in particular CD4+ T-cells that are preferentially infected by HIV, are essential for providing protective immunity against Mycobacterium tuberculosis (Mtb) infection, but also act as drivers of lung pathology and mediators of TB transmission. For most of its evolutionary history, Mtb has evolved in the absence of HIV co-infection. We thus hypothesize that the immunocompromised human host environment affects Mtb fitness, both by altering the immune environment within host and by altering transmission dynamics. Methods: We collected Mtb isolates and clinical data from HIV co-infected (HIV+) and HIV uninfected (HIV-) adults with pulmonary TB in nine high-burden countries in Africa, Asia and Latin America, as well as Switzerland. We inferred phylogenetic reconstruction by maximum likelihood methods and compared terminal branch lengths by HIV status and CD4 cell counts. We also compared the genetic diversity of human T-Cell epitope regions in HIV+ and HIV- patients. Results: Out of 908 Mtb strains, 458 came from HIV+ and 450 from HIV- patients. Isolates from all four main Mtb lineages (L1, L2, L3 and L4) responsible for the global TB epidemic are represented in our dataset, although L4 was the most frequent (62%). The phylogenetic tree of all isolates revealed no particular subdivision by HIV status (Figure 1). Terminal branches of the phylogenetic tree contained more mutations in HIV+ patients than in HIV- (p-value <0.001). This indicates that Mtb isolated from HIV+ individuals have a higher number of mutations that are not shared by other isolates in the population, possibly reflecting a lower transmission potential of HIV co-infected patients. The human T-cell epitopes of Mtb are known to be hyper-conserved compared to the rest of the genome, suggesting that immune recognition is required for successful Mtb transmission. We find the human T-cell epitopes of Mtb/HIV+ individuals harboured more mutations than Mtb/HIV- individuals, indicating less stringent purifying selection. Conclusion: Our study is consistent with findings from epidemiologic studies indicating reduced transmission of Mtb from HIV+ patients. The findings also reinforce our current understanding of epitope conservation in Mtb and brings new insights which could be used in the design of TB vaccines in HIV co-infected population.

Poster Abstracts

724 EVALUATION OF PULMONARY TUBERCULOSIS FOLLOWING IPT IN KENYAN ADULTS LIVING WITH HIV

Jill K. Gersh 1 , Daniel Matemo 2 , John Kinuthia 2 , Zachary Feldman 3 , Sylvia LaCourse 1 , Alex J. Warr 1 , Ruanne V. Barnabas 1 , Maureen Kamene 4 , David Horne 1 1 University of Washington, Seattle, WA, USA, 2 Kenyatta National Hospital, Nairobi, Kenya, 3 Seattle University, Seattle, WA, USA, 4 Ministry of Health, Nairobi, Kenya Background: Isoniazid preventive therapy (IPT) is a proven intervention to reduce tuberculosis (TB)-related morbidity and mortality among people living with HIV (PLHIV). The World Health Organization (WHO) recommends a symptom screen to rule-out TB prior to administering IPT. Previous studies have shown decreased sensitivity of the symptom screen in ART-treated individuals. TB incidence following IPT administered under programmatic conditions has not been well-described. We performed a study in Kenya to assess the incidence of TB in IPT-naïve and -treated individuals receiving ART and to assess the accuracy of the WHO symptom screen and other tests for the rule-out of TB disease. Methods: We enrolled PLHIV at two HIV care clinics in Nyanza region, Kenya. Patients who were IPT-naïve or had completed IPT at least 6 months prior to enrollment were eligible. We collected demographic, clinical, and laboratory data including blood for potential TB biomarkers (C-reactive protein [CRP], HIV viral load, CD4 count, monocyte:lymphocyte ratio, platelets, hemoglobin), and sputum sample for AFB-smear, -culture, and GeneXpert MTB/RIF (Xpert) testing. In bivariate analyses, we assessed the relationship between TB (culture- positive), and clinical characteristics (body mass index [BMI], antiretroviral therapy [ART]), WHO TB symptom screen, and potential TB biomarkers. Results: Between March 2017 and June 2018, we enrolled 389 participants (Table). 87.8% of participants had previously received IPT (median days since IPT completion=394 [280-539 IQR]). TB was diagnosed in 5 participants (1.3%, 95% confidence interval [CI] 0.4–3.0%), and was higher among IPT-naïve (4.3%, 95% CI 0.5-14.5%) than IPT-treated (0.9%, 95% CI 0.2-2.6%) participants. The rate of TB following completion of IPT was 0.8 per 100 person-years (95% CI 0.3 – 2.4). Among the 3 participants with post-IPT TB, 2 had a prior history of treated TB disease. One participant was diagnosed with INH-resistant TB. All participants diagnosed with TB had negative WHO symptom screens, negative AFB-smears, and 4 of 5 had negative Xpert testing. The sensitivity of all candidate biomarkers for TB was poor including CRP >8 mg/L (40%); hemoglobin <10g/dl had the best performance (60% sensitivity, 86% specificity). Conclusion: IPT provided under programmatic conditions is effective. The WHO symptom screen and candidate tests were insensitive for TB disease in PLHIV on ART. A positive history of TB may be a risk factor for TB after IPT.

CROI 2019 279