CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

686 ISLATRAVIR METABOLIC OUTCOMES IN PHASE IIB TRIAL OF TREATMENT- NAIVE ADULTS WITH HIV-1 Grace A. McComsey 1 , Jean-Michel Molina 2 , Yazdan Yazdanpanah 3 , Edwin DeJesus 4 , Stephanie O. Klopfer 5 , Anjana Grandhi 5 , Karen Eves 5 , Todd A. Correll 5 , Michael N. Robertson 5 , Carey Hwang 5 , George J. Hanna 5 , Peter Sklar 5 1 University Hospitals Cleveland Medical Center, Cleveland, OH, USA, 2 St. Louis Hospital, Paris, France, 3 AP–HP, Hôpital Bichat-Claude Bernard, Paris, France, 4 Orlando Immunology Center, Orlando, FL, USA, 5 Merck & Co, Inc, Kenilworth, NJ, USA Background: Islatravir (ISL, MK-8591) is the first nucleoside reverse transcriptase translocation inhibitor (NRTTI) in development for the treatment of HIV-1 infection. Decreases in bone mineral density (BMD) and changes in body fat have been reported in people taking antiretroviral therapy for HIV-1. We evaluated changes in BMD and body fat distribution, as well as related metabolic endpoints (weight, body mass index [BMI], fasting glucose and lipid levels), in a Phase 2B trial of treatment-naïve adults with HIV-1 who received ISL as part of a combination antiretroviral regimen for up to 48 weeks. Methods: In this randomized, double-blind, dose-ranging trial, participants were initially assigned to receive once-daily ISL (0.25 mg, 0.75 mg, or 2.25 mg) with doravirine (DOR, 100 mg) and lamivudine (3TC, 300 mg) or a fixed-dose combination of DOR, 3TC, and tenofovir disoproxil fumarate (DOR/3TC/TDF). Participants receiving ISL who achieved HIV-1 RNA <50 copies/mL at Week 20 or later stopped taking 3TC at their next study visit and continued DOR+ISL at the initial dosage (most participants stopped 3TC at Week 24). Hip BMD, spine BMD, peripheral fat, and trunk fat were assessed by dual-energy x-ray absorptiometry (DEXA) performed in all randomized participants at Weeks 0 and 48 and evaluated by a central imaging reader. Change (with 95% confidence interval) from baseline to Week 48 was calculated for each of the DEXA endpoints, weight, BMI, and fasting plasma levels of glucose, total cholesterol, high- density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides. Results: A total of 121 participants (92.6%male, 76.0%white, mean age 31 years) received study therapy and were included in the analyses. At baseline, the mean CD4+ T-cell count was 492 cells/mm 3 and 22% of participants had HIV-1 RNA >100,000 copies/mL. Changes in metabolic endpoints from baseline to Week 48 are shown below (see table). Conclusion: The ISL regimens, regardless of dose, demonstrated minimal impact on BMD and similar changes in fat distribution, weight, and BMI compared to the DOR/3TC/TDF group, through 48 weeks of treatment.

Methods: We merged data from two surveys conducted among PLWH (n=510) and the general population (n=2747) by KHANA Center for Population Health Research (nongovernmental organization) in 2015 and by the University of Health Sciences in 2016, respectively. Both employed a standardized questionnaire and physical/biochemical measurement protocols developed by the World Health Organization (STEPwise Approach to Surveillance or STEP survey or STEPS) and were conducted across selected provinces in Cambodia. We computed NCD prevalence and performed logistic regression to examine the relationship between NCDs and HIV while adjusting for age, sex, residence types, behavioral risk factors (such as smoking, heavy alcohol consumption, less than 5 servings of fruits and vegetables and low physical activity) and body mass index (BMI). Results: The prevalence was 9% (n=46) for diabetes, 13% (n=67) for hypertension and 3% (n=16) for high cholesterolemia among PLWH, all of which (except diabetes) were lower than that of the general population. Half of PLWH had prediabetes compared with only 16% of the general population. In logistic regression, PLWH were more likely to present prediabetes, aOR=6.94 (95% CI: 5.41, 8.90) and diabetes, aOR=1.41 (95% CI: 0.95, 2.09), and less likely to present hypertension and high cholesterolemia, aOR=0.59 (95% CI: 0.42, 0.81) and aOR=0.13 (95% CI: 0.08, 0.23), respectively. Conclusion: In Cambodia, compared to the general population, PLWH had an alarmingly high prevalence of prediabetes and, to a lesser extent, diabetes, while hypertension, prehypertension, high and borderline-high cholesterolemia appeared to be significantly lower. Differences in the host factors, the ART regimen and the traditional risk factor distribution could explain these contrasting findings in certain conditions in most Western studies. Our findings underscore the need to put in place proper measures to address prediabetes and diabetes among this vulnerable population.

Poster Abstracts

688 VALIDATION OF THE D:A:D CHRONIC KIDNEY DISEASE RISK SCORE IN A LARGE AFRICAN COHORT Firmin N. Kabore 1 , Armel Poda 2 , Karen Malateste 3 , Akouda Patassi 4 , Henri Chenal 5 , Eugène Messou 6 , François Dabis 3 , Didier K. Ekouevi 3 , Antoine Jaquet 3 , Amandine Cournil 7 , for the IeDEA West Africa Collaboration 1 IRD, Montpellier, France, 2 Centre MURAZ, Bobo-Doulasso, Burkina Faso, 3 INSERM, Bordeaux, France, 4 CHU de Sylvanus Olympio, Lome, Togo, 5 CIRBA, Abidjan, Côte d'Ivoire, 6 CePReF, Abidjan, Côte d'Ivoire, 7 Université de Montpellier, Montpellier, France Background: A prognostic risk score for chronic kidney disease (CKD) in persons living with HIV (PLHIV) has been developed using data from the D:A:D cohort (PLoS Med. 2015;12(3):e1001809) but this score has not been validated in sub- Saharan Africa. We assessed performance of the D:A:D risk score in a large cohort of PLHIV in West Africa. Methods: We used longitudinal data from 15,528 PLHIV initiating antiretroviral treatment between 1996 and 2018 in 4 clinics in Burkina Faso (n=1), Côte d’Ivoire (n=2), Togo (n=1) participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) West Africa collaboration. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Participants included had ≥3 creatinine measurements, a follow-up in the cohort ≥3 months and a baseline eGFR >60 ml/min/1.73m². CKD was defined as a confirmed (>3 months apart) eGFR ≤ 60 ml/min/1.73m². The risk score (short version) was calculated based on age, gender, nadir CD4 and baseline eGFR and categorized as low (<0), medium (0-4) and high (≥5) risk groups. Discrimination

687 NONCOMMUNICABLE DISEASES AND RISK FACTORS AMONG PEOPLE LIVING WITH HIV IN CAMBODIA Kennarey Seang 1 , Vonthanak Saphonn 2 , Marjan Javanbakht 1 , Sung-Jae Lee 1 , Phearavin Pheng 2 , Phalla Chea 2 , Sovannary Tuot 3 , Siyan Yi 3 , Pheak Chhoun 3 , Pamina M. Gorbach 1 1 University of California Los Angeles, Los Angeles, CA, USA, 2 University of Health Sciences, Phnom Penh, Cambodia, 3 KHANA Center for Population Health Research, Phnom Penh, Cambodia Background: HIV and antiretroviral therapy (ART) had been linked with increased risk of non-communicable diseases (NCDs) such as diabetes and hypertension alongside other well-established traditional risk factors. Empirical evidence from low- and middle-income countries (LMICs) on this relationship are scarce. Therefore, we examined the prevalence of NCDs in people living with HIV (PLWH) and the general population in Cambodia to assess the contribution of HIV and ART on NCDs and identify if locally adapted policies and/ or interventions are needed.

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