CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

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Early vs Deferred HIV Therapy and Cardiovascular Disease in People With HIV: The START Study Nila J. Dharan 1 , Shweta Mistry 2 , Alejandro Arenas-Pinto 3 , Daniel Duprez 2 , Vicente Estrada 4 , Karen Ha 5 , Mariana Kundro 6 , Rosie Mngqibisa 7 , Henry Mugerwa 8 , Rakan Nassreddine 9 , Tess Peterson 10 , Irini Sereti 11 , Janine Trevillyan 12 , Jason Baker 2 , Gail Matthews 13 , for the INSIGHT START Study Group 1 University of New South Wales Sydney, Sydney, Australia, 2 University of Minnesota, Minneapolis, MN, USA, 3 MRC Clinical Trials Unit at UCL, London, UK, 4 Hospital Universitario Clínico San Carlos, Madrid, Spain, 5 Cooper University Hospital, Camden, NJ, USA, 6 Hospital Ramos Mejia, Buenos Aires, Argentina, 7 Enhancing Care Foundation, Durban, South Africa, 8 Joint Clinical Research Centre, Kampala, Uganda, 9 Saint-Pierre University Hospital, Brussels, Belgium, 10 The Johns Hopkins University, Baltimore, MD, USA, 11 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 12 Austin Health, Melbourne, Australia, 13 Kirby Institute, Sydney, Australia Background: Cardiovascular disease (CVD) risk is higher in people with HIV (PWH) than people without HIV. However, whether this elevated risk of CVD is present in antiretroviral therapy (ART)-naïve PWH with high CD4+ counts, and whether delayed initiation of ART worsens CVD outcomes is unknown. Methods: The Strategic Timing of Antiretroviral Treatment (START) study randomized ART-naïve adults with HIV and CD4+ counts>500 cells/µL to immediate vs. deferred (until CD4 count <350/µL or AIDS developed) ART initiation. We report CVD event rates (composite of MI, stroke, coronary revascularization, or death from CVD) between treatment arms in three time

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Epidemiology of Coronary Atherosclerosis Among People Living With HIV in Uganda Mark J. Siedner 1 , Brian Ghoshhajra 1 , Geoffrey Erem 2 , Rita Nassanga 2 , Mangun Randhawa 1 , Moses Acan 3 , Zahra Reynolds 1 , Flavia Atwiine 3 , Edna Tindimwebwa 4 , Ntobeko Ntusi 5 , Alexander Tsai 1 , Susanne Hoeppner 1 , Chris Longenecker 6 , Samson Okello 3 , Stephen Asiimwe 4 , for the Uganda CAD (Coronary Artery Disease) Study Team 1 Massachusetts General Hospital, Boston, MA, USA, 2 Makerere University College of Health Sciences, Kampala, Uganda, 3 Mbarara University of Science and Technology, Mbarara, Uganda, 4 Kabwohe Clinical Research Center, Kabwohe, Uganda, 5 South African Medical Research Council, Cape Town, South Africa, 6 University of Washington, Seattle, WA, USA Background: HIV is an established risk factor for coronary atherosclerotic disease (CAD) in the United States and Europe. However, data linking HIV infection with coronary atherosclerosis in the African region are lacking.

Oral Abstracts

Methods: We enrolled people living with HIV (PWH) over 40 and on antiretroviral therapy (ART) for a minimum of three years from public-sector HIV clinics in Uganda. We then used population census data to recruit age- and sex-similar comparators without HIV (PWoH) from the same resident communities. Participants underwent cardiovascular disease (CVD) risk profiling and computed tomography (CT), including coronary artery calcium (CAC) scoring and coronary CT angiography (CCTA) for detection of CAD. Our primary outcome of interest was CAD, defined by presence of calcified or non-calcified plaque. Prespecified secondary outcomes were prevalence of non-calcified plaque, coronary artery segment involvement score, Agatston calcium score, and Coronary Artery Disease Reporting and Data System (CAD-RADS) Score. We fit multivariable regression models with HIV as the primary exposure of interest before and after adjustment for CVD risk factors or the atherosclerotic cardiovascular disease (ASCVD) risk score. Results: Out of 627 eligible individuals recruited, 586 met inclusion criteria and had evaluable images for interpretation. 287 (49.0%) were PWH, of whom over half (52%) had a CD4 count >500 cells/µL and most of whom (272/287, 95%) were virologically suppressed. PWH and PWoH were similar in age (57 years), proportion female (49%) and median ASCVD 10-year risk scores (3.4 vs. 4.1, P=0.30). Prevalence of CAD was low overall (54/586, 7.7%) and similar between PWH (26/287, 9.1%) and PWoH (19/299, 6.4%; absolute difference 2.7%, 95%CI -1.6, 7.0%). Findings were similar in multivariable regression models adjusted for CVD risk factors (adjusted prevalence ratio for PWH vs. PWoH 1.57, 95%CI 0.90, 2.74, P=0.11). Among those with plaque, prevalence of non-calcified plaque was similar between groups (8/26, 30.8% vs 5/19, 26.3%, P=0.60). Only 3 (0.5%) participants had an Agatston calcium score >100. No participants had a CAD-RADS score >2. Conclusions: We found no difference in the prevalence of CAD or non-calcified plaque between PWH and PWoH in Uganda in the ART era. Our observations confirm smaller hospital-based studies demonstrating extremely low of CAD compared to populations in the Global North and suggest that CAD may not be a major cause of morbidity in PWH in Uganda.

periods: (i) pre-2016 (ART use differed by treatment arm); (ii) post-2016 (study was unblinded and continuous ART use was recommended for both groups, 2016-2021); and (iii) over the entire study. Subgroup analyses were performed according to baseline demographic, clinical characteristics and CVD risk factors. Time-to-event methods compared event rates between study arms. Results: Overall, 4,684 participants were randomized (median age 36 yrs, 27% female, 30% Black race); 4436 (95%) had data available after 2016. At baseline, 32% were smokers, 17% had a BMI≥30 kg/m 2 , and the median Framingham 10-yr risk score was 1.9%. Comorbidities included hypertension (19%), dyslipidemia (8%), and diabetes (3%); 0.8% had prior CVD. Composite CVD event rates were similar between treatment arms during the pre- and post 2016 periods: 0.18 and 0.17 per 100 person yrs (PY) pre-2016 in the immediate and deferred arms, respectively, and 0.16 and 0.17 per 100 PY post-2016 in the immediate and deferred arms, respectively (Figure 1). Over the entire study (median follow-up of 9.3 yrs), 71 participants (35 immediate, 36 deferred) had a CVD event. There was no difference in events between arms (immediate/ deferred hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.61-1.56) for the composite CVD outcome or its components. Immediate vs. deferred ART was associated with a reduced risk of CVD in women (HR 0.19; CI 0.04-0.86) but not in men (HR 1.33; CI 0.79-2.24), p-value for interaction=0.014; interpretation is limited by low numbers of events. Conclusions: While immediate ART is known to reduce the risk of many clinical comorbidities and adverse outcomes among PWH, we did not find an effect of early ART initiation for reduction of CVD events among individuals at low CVD risk and moderate to high CD4 counts in the START study. The benefit found among women warrants further evaluation.

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CROI 2025