PREVALENCE AND CORRELATES OF SARS-CoV-2 VACCINE HESITANCY AMONG US PEOPLE WITH HIV

Background: People with HIV (PWH) have a higher risk of COVID-19 morbidity and mortality. SARS-CoV-2 vaccination is highly effective in preventing severe COVID-19, although medical mistrust may contribute to vaccine hesitancy among PWH. Method(s): PWH from 8 sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) completed the clinical assessment of patient-reported outcomes including a vaccine hesitancy instrument as part of routine care from 2/21-4/22. Participants were defined as vaccine hesitant if they had not yet received the SARS-CoV-2 vaccine and would probably or definitely not receive it. We assessed factors associated with SARS-CoV-2 vaccine hesitancy using logistic regression, and adjusted for demographics, unsuppressed viral load >200 copies/mL, calendar month and time on ART. Result(s): Overall, 3,278 PWH with a median age of 55 responded;19% were female sex at birth;93% were virally suppressed. At the time of survey, 27% reported they had not received the SARS-CoV-2 vaccine, of whom 27% (n=242;7% overall) reported vaccine hesitancy. Of these 242, 82% expressed concerns about vaccine efficacy;86% about side effects;38% reported distrust of healthcare, 53% reported concerns about vaccine contents (i.e. trackers, live virus);and 24% did not perceive risk from COVID-19. Factors associated with vaccine hesitancy included female sex (Adjusted Odds Ratio [AOR] 2.0;95% Confidence Interval (CI): 1.5-2.8;Table), Black vs. White race (AOR 1.8;95% CI: 1.3-2.5), age< 30 years (AOR 2.8;95% CI: 1.5-5.2), South/Midwest vs. Northeast region (AOR 1.7;95% CI: 1.2-2.4), years on ART (0.8;0.7-0.9) and unsuppressed viral load (AOR 2.2;95% CI: 1.4-3.5). Hesitancy decreased over time (AOR 0.9 per month;95% CI: 0.8-0.9). Vaccine side effects were the primary concern for women;vaccine contents for Black PWH and those who were unsuppressed;and lack of perceived COVID-19 risk for youth. Conclusion(s): Vaccine hesitancy was reported by approximately 7% of a U.S. multi-site cohort of PWH, and it was more prevalent among Black PWH, women, youth, those with unsuppressed viral loads, and residents of the South/ Midwest. The association between virologic non-suppression and vaccine hesitancy highlights the intertwined challenge of medical mistrust for both HIV and COVID-19. Although vaccine hesitancy decreased over time, renewed efforts will be needed to address concerns of PWH about the COVID-19 vaccine, given the ongoing need for revaccination with the evolution of the pandemic.

Viral Suppression Trajectories Destabilized after Covid-19 among Us People with Hiv

Background: Disruptions in clinical services during the COVID-19 pandemic could compromise past progress towards meeting U.S. Ending the HIV Epidemic (EHE) goals. We examined changes in the proportion with virologic suppression (VS) before and since the onset of COVID-19 in a multi-site U.S. cohort of people with HIV (PWH) using an interrupted time series design. Method(s): We assessed VS (< 200 copies/mL) trajectories 1/1/2018-1/1/2022, comparing trends before and after March 21, 2020 at 8 HIV clinics within the U.S. Center for AIDS Research Network of Integrated Clinical Systems (CNICS'). Hierarchical mixed-effects logistic regression and interrupted time series analyses examined changes in the trend (i.e., slope) of VS over time, and maximum likelihood estimation was used to account for missing VS data among those lost to follow-up (LTFU) post-COVID-19. Analyses were adjusted for demographics, site, CDC transmission group, CD4 nadir, VS, time on ART. Result(s): Data from 17,999 participants were included, providing a total of 120,918 VS assessments. Median age was 53 (interquartile range 42-61);19% were female sex at birth;the mean time on ART was 9.5 years;18% were unsuppressed at any point;17.7% were LTFU. Among the overall population, prior gains in VS slowed during COVID-19 (adjusted odds ratio [AOR] 0.93 per quarter-year;95% CI: 0.88-0.98;p=0.004;Figure). Greater impacts occurred among women (AOR 0.90;95% CI 0.81-0.99;p=0.05), persons with a history of injection drug use (PWID) (AOR 0.77 95% CI: 0.66-0.90;p=0.001), and Black PWH (AOR 0.90;95% CI: 0.84-0.96;p=0.001) in whom prior positive VS trends plateaued or began to reverse (Figure). VS remained lower among those with unstable housing (AOR 0.44;95% CI: 0.40-0.50;p< 0.001) but stayed unchanged from the pre-pandemic period. Conclusion(s): Previous gains in VS slowed during the COVID-19 pandemic among PWH in a multi-site network of U.S. HIV clinics. Known disparities in VS according to housing status remain unchanged, but VS disparities worsened for PWH who were women, PWID, or Black. Changes in VS trends could be related to socioeconomic impacts of the pandemic, insurance lapses, reduction of in-person clinic services, fear of coming to clinics, or other factors. Renewed investment in HIV public health and clinical services will be vital to achieve the U.S. EHE goals following COVID-19, with additional targeted interventions to support key populations with persistent or worsening disparities needed.

EXERCISE CAPACITY IS REDUCED IN HIV INDEPENDENT OF SARS-CoV-2 INFECTION

Background: Reduced exercise capacity occurs as a post-acute sequela of COVID-19 ("PASC" or "Long COVID"). Cardiopulmonary exercise testing (CPET) is the gold standard for measuring exercise capacity and identifying reasons for exercise limitations. Only one prior study used CPET to examine exercise limitations among people living with HIV (PLWH). Extending our prior findings in PASC, we hypothesized that PLWH would have a greater reduction in exercise capacity after SARS-CoV-2 co-infection due to chronotropic incompetence (inability to increase heart rate). Method(s): We performed CPET within a COVID recovery cohort that included PLWH (NCT04362150). We evaluated associations of HIV and prior SARS-CoV- 2 infection with or without PASC with: (1) exercise capacity (peak oxygen consumption, VO2) and (2) adjusted heart rate reserve (AHRR, marker of chronotropic incompetence) using linear regression with adjustment for age, sex, and body mass index. Result(s): We included 83 participants (median age 54, 35% female, 10% hospitalized, 37 (45%) PLWH) who underwent CPET at 16 months (IQR 14-17) after SARS-CoV-2 infection. Among PLWH (median duration living with diagnosed HIV 21 years (IQR 15-28), all virally suppressed on antiretroviral therapy), 14 (39%) had not had SARS-CoV-2 infection, 12 (32%) had prior SARSCoV- 2 infection without PASC, and 11 (30%) had PASC (Long COVID symptoms at CPET). Median CD4 count was 608 (370-736) and CD4/CD8 ratio 0.92 (0.56-1.27). Peak VO2 was reduced among PLWH compared to individuals without HIV with an achieved exercise capacity only 80% vs 99% (p=0.005, Fig.), a difference in peak VO2 of 5.5 ml/kg/min (95%CI 2.7-8.2, p< 0.001). Exercise capacity did not vary by SARS-CoV-2 infection among PLWH (p=0.48 for uninfected vs infected;p=0.25 for uninfected vs no PASC;p=0.32 no PASC vs PASC). Chronotropic incompetence was present in 38% of PLWH vs 11% without HIV (p=0.002), and AHRR (normal >80%) was significantly reduced among PLWH vs individuals without HIV (60% vs 83%, p< 0.0001, Fig.). Heart rate response varied by SARSCoV- 2 status among those with HIV: namely, 3/14 (21%) without SARS-CoV-2, 4/12 (25%) with SARS-CoV-2 without PASC, and 7/11 (64%) with PASC (p=0.04 PASC vs no PASC). Among PLWH, CD4 count, CD4/CD8 ratio, and hsCRP were not associated with peak VO2 or AHRR. Conclusion(s): Exercise capacity is reduced among PLWH, with no differences by SARS-CoV-2 infection or PASC. Chronotropic incompetence may be a mechanism of reduced exercise capacity among PLWH. (Figure Presented).

INCREASED HIV VIRAL SUPPRESSION during COVID-19 among US URBAN PEOPLE with HIV

Background: After COVID-19 shelter-in-place (SIP) orders on 3/16/2020, viral suppression (VS) rates initially decreased within a safety-net HIV clinic in San Francisco, with greater decreases among homeless people living with HIV (PLWH). We sought to understand if (1) proactive outreach to provide social services, (2) scaling up of in-person visits for most patients and drop-in visits at the clinic, and (3) expansion of housing programs could reverse this decline. Methods: We assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression and propensity score methods, followed by interrupted time series (ITS) analysis to examine changes in the rate of viral suppression per month. Loss to follow-up was assessed via active clinic outreach and tracing using Kaplan-Meier methods. Results: The cohort contained 1816 patients with a median age of 51;12% female, 14% unstably housed, and 15% with CD4+-cell counts <200 cells/mm3. The adjusted odds of VS increased 1.34-fold following the intervention (95% CI: 1.21-1.46), with similar results using inverse probability weighting (adjusted odds ratio (AOR) 1.31;95% CI: 1.17-1.46). Results from the ITS analysis show that the odds of VS continuously increased by 1.05-fold per month over the post-intervention period (95% CI: 1.01-1.08, Figure). Proactive phone outreach successfully reached 90.0% of the clinic to offer services. The one-year cumulative loss to follow-up rate was 3.2% (95% CI: 2.5-3.9%). The proportion of total attended visits that were telephone visits decreased from a maximum of 64.9% to a minimum of 10.1% at the end of the analysis period. The rate of viral load monitoring decreased by 15% after the institution of SIP (95% CI: 0.83-0.88). Among homeless PLWH, the AOR for VS was 1.70 (95% CI: 1.24-2.34) and there was a 5.9% increase in VS per month using ITS methods (95% CI: 1.0-12.3%). Conclusion: After an initial destabilization in VS in a large safety-net clinic following SIP orders, the VS rate increased following scale-up of in-person visits, clinic outreach to patients, intensification of social services during this time, and access to COVID-related housing programs. The loss to follow-up rate was similar or lower compared to prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing assistance programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.

Lower SARS-CoV-2 IgG and Pseudovirus Neutralization Titers Post-mRNA Vaccination among People Living with HIV

Background. Limited data are available on whether there are differences in the immune response to SARS-CoV-2 vaccination by HIV status or by mRNA vaccine type. Methods. We saved residual outpatient laboratory samples of all previously mRNA-vaccinated individuals in the adult medicine clinics of a public hospital with a large outpatient HIV clinic during May 2021, and then excluded individuals with prior SARS-CoV-2 infection. We next 1:1 matched 100 PLWH to 100 outpatient HIVnegative adult medicine patients receiving care for chronic medical conditions on days since completion of second vaccination (minimum 10), sex, age +/-5 years, and the type of mRNA vaccine received. We defined a non-response as reciprocal pseudovirus neutralizing titer< 10 and anti-RBD IgG< 10 relative fluorescent units, and compared non-response by HIV status using mixed models. Results. In each matched group there were 13 women;25 received the mRNA-1273 vaccine and 75 received the BNT162b2 vaccine;the median age was 59. The median time from second vaccination was 35 days (IQR: 20-63). Among PLWH, the median CD4+ T-cell count was 511 (IQR: 351-796) and 5 individuals had HIV RNA > 200. We found 2.4-fold greater odds of pseudovirus neutralizing antibody non-response among PLWH compared to people without HIV (95% CI=1.1-5.4). Although few individuals in each group did not mount an IgG response (12 among PLWH vs. 5;p=0.08), continuous anti-RBD IgG concentrations were 43% lower among PLWH (95% CI=0.36-0.88). Among PLWH, when adjusting for age, sex, and days post-vaccination, each 100-cell increase in CD4+T-cell count was associated with 22% higher neutralizing antibody titers (GMR 1.22;95% CI=1.09-1.37). Unsuppressed HIV RNA >200 was associated with 89% lower neutralizing antibody titers (GMR 0.11;95% CI=0.01-0.84). Receipt of the BNT162b2 vs. mRNA-1273 vaccine was associated with 77% lower neutralizing titers (GMR 0.23;95% CI=0.08-0.65) among PLWH. Post-mRNA Vaccination SARS-CoV-2 IgG Concentrations and Pseudovirus Neutralizing Titers by HIV Status and Vaccine Conclusion. PLWH had lower than expected response to mRNA SARS-CoV-2 vaccines, with the highest non-response among those with low CD4+ counts, unsuppressed HIV RNA, and those who received the BNT162b2 vaccine. Immunization strategies to improve immune responses among PLWH should be studied, and may include booster vaccination or preference of the mRNA-1273 vaccine in this group.