CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

150

Community Health Worker-Facilitated Telehealth for Severe Hypertension Care in Kenya and Uganda Matt Hickey 1 , Asiphas Owaraganise 2 , Sabina Ogachi 3 , Norton M. Sang 3 , Erick Wafula Mugoma 3 , James Ayieko 3 , Jane Kabami 2 , Gabriel Chamie 1 , Elijah Kakande 2 , Maya L. Petersen 4 , Laura B. Balzer 4 , Diane Havlir 1 , Moses R. Kamya 5 1 University of California San Francisco, San Francisco, CA, USA, 2 Infectious Diseases Research Collaboration, Kampala, Uganda, 3 Kenya Medical Research Institute, Nairobi, Kenya, 4 University of California Berkeley, Berkeley, CA, USA, 5 Makerere University College of Health Sciences, Kampala, Uganda Background: Expanding the HIV care model to include HIV status-neutral hypertension treatment can improve cardiovascular disease outcomes; however, individuals with severe hypertension face additional barriers to care, including need for frequent clinic visits to titrate medications. We conducted a pilot study to test whether a clinician-driven, community health worker (CHW) facilitated telehealth intervention would improve hypertension control among adults with severe hypertension in rural Uganda and Kenya. Methods: We conducted a randomized controlled trial of hypertension treatment delivered via telehealth by a clinician (adherence assessment, counseling, decision-making) and facilitated by a CHW in the participant's home, compared to clinic-based hypertension care (NCT04810650). We recruited adults ≥40 years with BP ≥160/100 mmHg at household screening by CHWs, with no restrictions by HIV status. After initial evaluation at the clinic, participants were randomized to telehealth or clinic-based hypertension follow-up. All participants were treated using standard country guideline-based antihypertensive drugs. The primary outcome was hypertension control at 24 weeks (BP <140/90); secondary outcomes included severe hypertension (BP ≥160/100) and retention in care (not late by ≥30 days at 24 weeks). We used TMLE to compare outcomes by arm, overall and among key subgroups. Results: We screened 2,965 adults ≥40 years, identifying 266 (9%) with severe hypertension and enrolling 200 (102 control, 98 intervention). Participants were 70% women, median age 62 (IQR 51-72); 14% were HIV- positive. Mean number of hypertension drugs prescribed at last visit was 1.6 in intervention and 1.7 in control. Week 24 hypertension control was 77% in intervention and 52% in control (RR 1.48, 95%CI 1.20-1.83); effect on hypertension control was greater among women (81% vs 53%; RR 1.53, 95%CI 1.21-1.94). Prevalence of severe hypertension at 24 weeks was 7% in intervention and 25% in control (RR 0.30, 95%CI 0.14-0.64), with similar effects among people with HIV (8% vs 21%, RR 0.39, 95%CI 0.04-3.82). Retention in care at 24 weeks was 91% in intervention and 61% in control (RR 1.49, 95%CI 1.26-1.76). Conclusion: Clinician-driven, CHW-facilitated telehealth for hypertension management improved hypertension control and reduced severe hypertension compared to clinic-based care. Telehealth focused on individuals with severe hypertension is a high-yield approach to improve outcomes among those with highest risk for CVD. Pitavastatin Reduces Non-Calcified Plaque via Pro-Collagen PCOLCE Independently of LDL in REPRIEVE Márton Kolossváry 1 , Samuel R. Schnittman 1 , Markella Zanni 1 , Kathleen V. Fitch 1 , Carl J. Fichtenbaum 2 , Judith A. Aberg 3 , Gerald S. Bloomfield 4 , Judith S. Currier 5 , Marissa Diggs 1 , Chris deFilippi 6 , Sara McCallum 1 , Michael T. Lu 1 , Heather J. Ribaudo 7 , Pamela S. Douglas 8 , Steven Grinspoon 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 University of Cincinnati, Cincinnati, OH, USA, 3 Icahn School of Medicine at Mt Sinai, New York, NY, USA, 4 Duke University, Durham, NC, USA, 5 University of California Los Angeles, Los Angeles, CA, USA, 6 Inova Shar Heath and Vascular Hospital, Falls Church, VA, USA, 7 Harvard TH Chan School of Public Health, Boston, MA, USA, 8 Duke University School of Medicine, Durham, NC, USA Background: Pitavastatin reduced major adverse cardiac events (MACE) and non-calcified coronary artery plaque volume (NCPvol) among people with HIV (PWH) in REPRIEVE. However, the biological pathways responsible are not well understood. We utilized a targeted discovery proteomics approach to evaluate the biological pathways mediating statin effects on NCPvol in REPRIEVE. Methods: Changes in 255 plasma protein levels (Olink, see Figure 1) were analyzed among REPRIEVE mechanistic substudy participants continuing their assigned treatment over a 2-year follow-up period. Changes in protein levels were related to changes in NCPvol in mediation analysis among participants with evidence of plaque on baseline coronary CT angiography using linear regression analysis. Results: Among the 542 individuals (age: 51 years, 18% female) included in the assessment of protein changes, 275 received placebo and 267 pitavastatin. After correcting for false discovery rates, pitavastatin use was significantly associated

with increased expression of 3 proteins (PCOLCE, NRP-1, MIC-A/B) and decreased expression of 4 proteins (TFPI, TRAIL, ANGPTL3, MBL2, Figure 1). Among the 196 participants (107 pitavastatin, 89 placebo) with plaque at entry, while pitavastatin associated changes in LDL were observed, they did not correlate with NCPvol (ρ=0.08, p=0.20). However, among the proteins changing with pitavastatin, the increase in PCOLCE was significantly related to the reduction in NCPvol (ρ=-0.27, p<0.001). Mediation analysis including PCOLCE and LDL indicated that pitavastatin resulted in a 26% [CI: 16; 38%, p<0.001] increase in PCOLCE and a 30% [CI: 23; 37%, p<0.001] decrease in LDL. While each fold increase in PCOLCE was associated with a 25% decrease in NCPvol [CI: 13; 35%, p<0.001], LDL changes had no relationship (2%, CI: -12; 18%, p=0.82). Overall, 93% of the 8.8% reduction in NCPvol was mediated through the effects of pitavastatin on PCOLCE. Other proteins were either borderline or nonsignificant in the mediation analysis. Conclusion: The effects of pitavastatin to reduce NCPvol in REPRIEVE were significantly mediated by changes in PCOLCE, the rate-limiting enzyme in collagen deposition. Surprisingly, LDL change was not related to changes in NCPvol. Further studies will investigate if higher levels of PCOLCE mediates the beneficial effects of pitavastatin on MACE. Statin effects on collagen formation to stabilize noncalcified plaque may be an important unrecognized mechanism to reduce coronary artery disease in PWH.

Oral Abstracts

152

Pitavastatin Has No Effect on Long-Term, Objective Physical Function in REPRIEVE Kristine M Erlandson 1 , Triin Umbleja 2 , Heather J. Ribaudo 2 , Jennifer A. Schrack 3 , Edgar T. Overton 4 , Carl J. Fichtenbaum 5 , Kathleen V. Fitch 6 , Kenneth Wood 7 , Markella Zanni 6 , Gerald S. Bloomfield 8 , Pamela S. Douglas 8 , Steven Grinspoon 6 , Todd T. Brown 9 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4 University of Alabama at Birmingham, Birmingham, AL, USA, 5 University of Cincinnati, Cincinnati, OH, USA, 6 Massachusetts General Hospital, Boston, MA, USA, 7 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 8 Duke University, Durham, NC, USA, 9 The Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: Declines in physical function occur with age, and are common among people with HIV (PWH). Due in part to the anti-inflammatory effect, statins may alleviate declines in physical function though most studies assessing the effect of statins on physical function in the general population have been observational and randomized controlled data have been limited to one year of follow-up. We hypothesized that physical function would decline among PWH, but with the known anti-inflammatory effects of statins, PWH randomized to pitavastatin would have slower declines compared to placebo. Methods: REPRIEVE is a double-blind randomized trial evaluating pitavastatin for primary prevention of major adverse cardiovascular events in PWH; the PREPARE substudy assessed physical function in a subset of participants annually for up to 5 years. Chair rise rate based on time to complete 10 chair rises (primary outcome), 4-meter gait speed, grip strength, and a combined modified short physical performance test were analyzed using linear mixed models. Results: Of 602 PWH, 52% were randomized to pitavastatin and 48% to placebo. Median age was 51 years; 18% were natal female; 2% transgender; 40% Black, and 18% Hispanic; median BMI was 27.2 (Q1, Q3 24.3, 30.1) kg/m 2 . 45% of participants enrolled at REPRIEVE entry; 55% enrolled within 24 months

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CROI 2024