CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

805

Switching to Integrase Strand Transfer Inhibitors and the Risk of Diabetes in Persons With HIV Y Joseph Hwang 1 , Catherine Lesko 2 , Todd T. Brown 1 , Jeanne C. Keruly 1 , LaQuita N. Snow 1 , Jarratt D. Pytell 3 , Oluwaseun Falade-Nwulia 1 , Richard D. Moore 1 , Anthony Fojo 1 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 University of Colorado Anschutz Medical Campus, Aurora, CO, USA Background: Integrase strand transfer inhibitors (INSTIs) are commonly used antiretroviral therapy (ART) among people with HIV (PWH). INSTI use is associated with weight gain, hyperglycemia, and diabetes among ART-naïve PWH. We estimated the risk of incident diabetes associated with switching from a non-nucleoside reverse-transcriptase inhibitor (NNRTI) or protease inhibitor (PI) to an INSTI. Methods: We studied PWH aged ≥18 years in the Johns Hopkins HIV Clinical Cohort. PWH with no history of diabetes who had used NNRTI- or PI-based ART for ≥180 days were followed from attended HIV primary care visits between 2007 and 2022 until incident diabetes, last clinical encounter, or December 31, 2022. PWH who switched to bictegravir, dolutegravir, elvitegravir, or raltegravir were assigned to the INSTI group and PWH who were continued on an NNRTI or PI were assigned to the non-INSTI group. Incident diabetes was defined as a laboratory hemoglobin A1c value ≥6.5%, initiation of diabetes-specific drug, or initiation of non-specific diabetes drug and diabetes diagnosis with the International Classification of Diseases, Ninth or Tenth Revision codes. The association between ART exposure and incident diabetes was estimated using multivariable Cox proportional hazards models with the robust variance estimator to account for repeated observations on individuals. We adjusted for age, sex, race, year of cohort entry, body mass index, coronary artery disease, chronic kidney and liver diseases, cerebrovascular disease, dyslipidemia, heart failure, hypertension, and co-prescription of anticoagulants, antidepressants, antihypertensives, antiplatelets, antipsychotics, antilipemics, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF). Results: Our sample included 2,354 PWH, of whom 891 PWH switched to an INSTI and contributed an encounter to the INSTI group. 2,293 PWH contributed ≥1 encounters to the non-INSTI group. The median age was 49 years and 66% were male. Switching to any INSTI was not statistically significantly associated with an increased risk of diabetes (adjusted hazard ratio [aHR], 1.05; 95% confidence intervals [CI], 0.79–1.40). The hazard ratios for specific INSTIs were similar (Table). Conclusion: Switching from an NNRTI or PI to INSTI-based ART did not appreciably increase the risk of incident diabetes. These findings can inform antiretroviral prescribing in the common clinical scenarios, where switching to INSTI-based therapy is considered in the care of PWH. Effect of TDF and TAF on Duodenal Enterocytes: A Hypothesis for Different Effect on Body Weight Kai Kauppinen , Nelli Sjöblom, Inka Aho, Perttu Arkkila, Jussi Sutinen Helsinki University Central Hospital, Helsinki, Finland Background: Tenofovir disoproxil fumarate (TDF) when compared to tenofovir alafenamide (TAF) leads to lower body weight and plasma lipid concentrations; the mechanisms of these effects are unknown. TDF as opposed to TAF is processed into free tenofovir (TFV) within enterocytes when absorbed from proximal duodenum. The effect of TFV in enterocytes is unknown, but in kidney proximal tubular cells it may cause mitochondrial damage. We hypothesize that TDF may damage enterocytes leading to reduced absorption of nutrients from this anatomical site. Methods: People living with HIV without known gastrointestinal disease receiving stable TDF (n=12) or TAF (n=12) containing regimen underwent gastroscopy with biopsies from proximal and distal duodenum. Biopsies were scanned with Leica GT450 scanner and measurements taken in Neagen's neaLink digital pathology solution. Serum intestinal fatty acid-binding protein (I-FABP)

was measured as a circulating marker of enterocyte damage. Plasma/serum concentrations of nutrients absorbed from proximal duodenum were measured. Results: All participants were male. TDF and TAF groups were matched for third antiretroviral agent (58% integrase strand transfer inhibitor, 42% non nucleoside reverse transcriptase inhibitor) and age (mean (SD) TDF group 55 (12) and TAF group 57 (16) years). Five patients in TDF group (celiac disease, helicobacter gastritis and 3 cases of esophagitis) and 2 patients in TAF group (2 cases of esophagitis) had a pathological macroscopic or histologic finding (p=0.178). The patient with newly diagnosed celiac disease was excluded from the rest of the analyses. Duodenal villi were flatter, crypts deeper, and villus height to crypt depth ratio was lower in TDF vs TAF group, especially in proximal duodenum (Table 1). I-FABP concentration was significantly higher in TDF vs. TAF group (3.0 (1.07) vs. 1.8 (0.53) ng/ml, p=0.003). TDF group had numerically lower plasma/serum concentrations of iron, folate, vitamins A, B1, D and E, whereas β-carotene concentration was lower in TAF group. None of these differences were statistically significant. Conclusion: TDF group displayed signs of villous damage especially in proximal duodenum when compared to TAF group. This together with increased I-FABP suggest enterocyte damage and may contribute to the clinical effect of TDF on lowering body weight and plasma lipid concentrations when compared to TAF. Larger studies are needed to evaluate concentrations of nutrients absorbed from proximal duodenum among TDF users.

Poster Abstracts

807

Weight Change After Starting Doravirine Among ART-Experienced Individuals in the US Karam Mounzer 1 , Laurence Brunet 2 , Michael Sension 3 , Ricky K. Hsu 4 , Jennifer S. Fusco 2 , Yohance O. Whiteside 5 , Gregory P. Fusco 2 1 Philadelphia FIGHT, Philadelphia, PA, USA, 2 Epividian, Raleigh, NC, USA, 3 CAN Community Health, Sarasota, FL, USA, 4 AIDS Healthcare Foundation, New York, NY, USA, 5 Merck & Co, Inc, Rahway, NJ, USA Background: Weight gain has been associated with the use of antiretrovirals (ARV), especially with integrase inhibitors (INSTI) and tenofovir alafenamide (TAF), but less so with non-nucleoside reverse transcriptase inhibitors (NNRTI). In 2018, doravirine (DOR) became the latest NNRTI to be approved. We assessed changes in weight over time after starting DOR among virologically suppressed individuals. Methods:From the US-based OPERA cohort, ART-experienced adults with HIV who started a DOR-based regimen between 30AUG2018-30NOV2022 with a viral load <50 copies/mL were included (followed through 31MAY2023). Univariate linear mixed models were used to estimate rates of weight change on DOR; restricted cubic splines on time provided flexibility. Results were stratified by sex. Two sensitivity analyses were conducted to account for use of other ARVs before and after DOR start (a) restriction to those who maintained the same INSTI-TAF combination (b) stratification by efavirenz [EFV]-tenofovir disoproxil fumarate [TDF] use. Results: Of 388 included individuals, 79% were men, 33% were Black, and 78% were overweight or obese (BMI ≥25 kg/m 2 ) at DOR start. Most regimens prior to DOR start included an INSTI with TAF (47%) or an INSTI without TAF (31%); 16% included TAF without an INSTI and 7% included neither INSTI nor TAF. DOR was combined with both INSTI and TAF (31%), with INSTI without TAF (30%), with TAF without INSTI (11%) or with neither (28%). Overall, people starting DOR lost a statistically significant average of 0.80 kg/year (95% CI: -1.32, -0.28).

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CROI 2024 244