CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: EMPIRICAL is a randomized clinical trial (#NCT03915366) funded by EDCTP (RIA2017MC-2013) investigating the impact of empirical treatment of cytomegalovirus and/or TB treatment on mortality in infants living with HIV hospitalized with severe pneumonia in six African countries. Infants with clinical or confirmed TB diagnoses are excluded from entry, as are infants with close TB contacts. At enrollment, stool and nasopharyngeal aspirates are collected for Xpert Ultra testing, and urine for lipoarabinomannan (LAM). TB culture was not performed. Infants enrolled between March 2020-July 2023 were included in this interim analysis. Results: Laboratory-confirmed TB was present in 23% (114/496) infants; 96% (109/114) presented with >1 Graham clinical criteria and 71% (81/114) with >2. The distribution of patients with specific clinical criteria is shown in Figure 1. Persistent cough was the only criteria with a significant relative risk for laboratory-confirmed TB (1.51 [1.12;2.05], p=0.008). The presence of >1 clinical criteria had a sensitivity of 96%, specificity of 8.1%, positive predictive value (PPV) of 32.3%, and negative predictive value (NPV) of 80% for laboratory confirmed TB. The presence of >2 criteria had sensitivity of 71.1%, specificity of 42.7%, PPV of 36.3% and NPV of 76.3%. Conclusion: Despite excluding the patients most likely to have TB, almost one quarter of infants living with HIV hospitalized with severe pneumonia had Xpert or LAM-confirmed TB after study enrollment, and almost all of them had at least one of the signs/symptoms in the Graham clinical criteria, suggesting that these criteria are valid for this specific patient population.

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Causes of Death After Early ART in Infants Living With HIV From 3 Sub-Saharan African Countries Alfredo Tagarro 1 , Sheila Fernández-Luis 1 , Sara Dominguez-Rodriguez 1 , Alvaro Ballesteros 1 , Louise Kuhn 2 , Mark F. Cotton 3 , Carlo Giaquinto 4 , Paolo Rossi 5 , Moira Spyer 6 , Kennedy Otwombe 7 , Osee Behuhuma 8 , Paula Vaz 9 , Caroline Foster 10 , Pablo Rojo 1 , for EPIICAL 1 Hospital Universitario 12 de Octubre, Madrid, Spain, 2 Columbia University, New York, NY, USA, 3 Stellenbosch University, Cape Town, South Africa, 4 University of Padova, Padova, Italy, 5 Bambino Gesu Children's Hospital, Rome, Italy, 6 University College London Hospitals NHS Trust, London, United Kingdom, 7 Perinatal HIV Research Unit, Soweto, South Africa, 8 Africa Health Research Institute, Mtubatuba, South Africa, 9 Fundação Ariel Glaser Contra o SIDA Pediátrico, Maputo, Mozambique, 10 Imperial College Healthcare NHS Trust, London, United Kingdom Background: Despite comprising only 4% of all positive people, children account for 15% of all HIV/AIDS-related deaths. Mortality unrelated to AIDS is also high in LMIC. We investigated causes of death, potential relationship with HIV infection, and associated factors in a cohort of early treated children. Methods: From May 2018 to May 2021, we recruited infants who initiated ART within the first 6 months of life and within 3 months of diagnosis. Follow-up was 4 years. There were 6 study sites in South Africa, Mozambique and Mali. HIV/AIDS-related mortality was determined by an independent Endpoint Review Committee comprising three HIV Pediatric infectious disease specialists not directly involved in participant care. The experts assessed the relationship of each death to HIV advanced disease using available epidemiological, clinical, and laboratory data from the study database. Mortality risk factors were analyzed using a competing risk Cox multivariable regression model. Results: Of 215 infants enrolled, the median age at HIV diagnosis was 31 days with ART initiation at a median age of 34 days [IQR 26.0;73.0]. Follow-up was 34.0 months [IQR 16.3;44.1]. Median VL at ART initiation was log 4.95 [IQR 3.58;5.82] copies/mL. Twenty-five infants (11.6%) died at a median age of 5.3 months [IQR 3.0;9.6]. The probability of death within the first year of ART initiation was 12% (95%CI 6-14), and after 2 and 3 years, 12% (95% CI, 8-17). The primary causes of death were pneumonia (36%), unknown (24%), tuberculosis (12%), malnutrition (8%), diarrhea (8%), sepsis (8%) and malaria (4%). Cause of death was assigned as likely HIV/AIDS-related in 8/25 (32%) of deaths. VL at ART initiation was significantly associated with all deaths (HIV/AIDS-related cause HR:3.0 (95%CI 1.3-7.1), p=0.014; unclear relation, HR:1.7 (95%CI 1.1-2.8), p=0.019). The more positive the CD4 slope, the lower the probability of death in HIV/AIDS-related (HR:0.7 (95%CI 0.5-1.0, p=0.067) or unrelated (HR:0.7 (95%CI 0.5-0.9), p=0.007). Patients from Mali had a higher probability of death from HIV/AIDS-unrelated causes , compared to those enrolled in South Africa (HR:13.8 [95%CI 1.92-98.8], p=0.009). Conclusion: Mortality, both related with HIV/AIDS or probably unrelated, were associated with baseline VL and poor CD4 restoration. However, the 3-fold risk for high baseline VL and HIV/AIDS-related causes supports a strong biological effect of baseline VL along with a challenging social environment. Usefulness of Clinical Signs for Tuberculosis Diagnosis in Infants Living With HIV With Pneumonia Tisungane Mvalo 1 , Cinta Moraleda 2 , William C. Buck 3 , Victor Musiime 4 , Sara Domínguez-Rodríguez 2 , Chishala Chabala 5 , Hilda A. Mujuru 6 , Alfredo Tagarro 2 , Pui-Ying Iroh Tam 7 , Jahit Sacarlal 8 , Abner Tagoola 9 , John Tembo 10 , Sheila Fernández-Luis 2 , Pablo Rojo 2 , for the EMPIRICAL Clinical Trial Group 1 University of North Carolina Project–Malawi, Lilongwe, Malawi, 2 Hospital Universitario 12 de Octubre, Madrid, Spain, 3 University of California Los Angeles, Los Angeles, CA, USA, 4 Makerere University, Kampala, Uganda, 5 University of Zambia, Lusaka, Zambia, 6 University of Zimbabwe, Harare, Zimbabwe, 7 Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi, 8 Universidade Eduardo Mondlane, Maputo, Mozambique, 9 Jinja Regional Referral Hospital, Jinja, Uganda, 10 University Teaching Hospital, Lusaka, Zambia Background: Children living with HIV are at increased risk of tuberculosis (TB) morbidity and mortality. However, TB diagnosis remains challenging, particularly in infants who have paucibacillary disease and are more likely to have atypical clinical presentations. Consensus case definitions based on microbiological confirmation, signs/symptoms, chest radiograph features, TB exposure/immunological evidence of infection, and response to treatment have been proposed by Graham et al. to standardize the reporting of cases of intrathoracic tuberculosis. We evaluated the prevalence of the Graham clinical criteria (persistent cough, weight loss/failure to thrive, persistent unexplained fever or lethargy, neonatal pneumonia or hepatosplenomegaly) in relation to confirmed TB diagnosis in infants living with HIV hospitalized with severe pneumonia.

Poster Abstracts

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Influence of Childhood Adversity on Cardiovascular Health in HIV Youth in Uganda Sahera Dirajlal-Fargo 1 , Shan Sun 1 , Christine Karungi 2 , Joy Gumikiriza-Onoria 3 , Angel Nanteza 3 , Nicholas Funderburg 4 , Victor Musiime 2 , Grace A. McComsey 5 , Reuben Robbins 6 1 Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA, 2 Joint Clinical Research Centre, Kampala, Uganda, 3 Makerere University College of Health Sciences, Kampala, Uganda, 4 The Ohio State University, Columbus, OH, USA, 5 Case Western Reserve University, Cleveland, OH, USA, 6 Columbia University, New York, NY, USA Background: Data suggest that adverse childhood experiences (ACEs) are associated with an increased risk of cardiovascular disease (CVD). However, little data exist on the effect of ACEs and health in children. We examined the relationship between ACEs and CVD risk factors in youth living with perinatally acquired HIV (YPHIV) in Uganda. Methods: A prospective observational cohort study was performed in 49 YPHIV and 51 HIV- from 2017-2021 at the JCRC in Uganda at baseline and 96 weeks later. All participants were between 10-18 years of age. YPHIVs were on ART with HIV-1 RNA level ≤400 copies/mL. Mean common carotid artery intima media thickness (IMT), pulse wave velocity (PWV), plasma and cellular markers of systemic inflammation and immune activation were evaluated at baseline and 96 weeks. The Adverse Childhood Experiences-International Questionnaire (ACEs), Patient Health Questionnaire-9 (PHQ-9) and socioeconomic questionnaires were administered, and ACEs sub scored of abuse, neglect and household dysfunction (HHDYS) were calculated. Hierarchical cluster analysis was performed to identify natural clusters of ACEs and socioeconomics. Results: At baseline, median age was 12 years (IQR: 11-14), 52% were female. YPHIV were more likely to have a history of abuse, and higher ACE total scores (p=0.015). Two optimal clusters were derived from ACEs, PHQ-9 mean scores, and socioeconomic variables (figure 1). Compared to cluster 1, participants in cluster 2 had higher ACEs (p≤0.001 for all), and were more likely to have: HIV (69% vs 42%, p=0.019), higher levels of monocytes and T cell activation

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