ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Background: There is mounting evidence regarding the frequency and spectrum of post-acute sequelae of SARS-CoV-2 infection (PASC), but a search for causes has been elusive. Recently, a plasma-based assay for SARS-CoV-2 antigen has been developed, which in initial use revealed that a high fraction of severely affected patients with PASC had circulating antigen. It is unknown whether detectable SARS-CoV-2 antigen is specific for PASC or how the assay performs in a broader clinical spectrum of patients with PASC. Method(s): We evaluated a cohort of patients with RNA-confirmed SARS-CoV-2 infection enrolled >=3 weeks following initial symptoms. Participants, both with and without PASC at enrollment, were identified via facility- and communitybased advertising and examined every 4 months. An interviewer-administered questionnaire ascertained presence of 30 different symptoms (new or worse compared to pre-COVID) in the prior 2 days at each exam. Using the single molecule array (Simoa) assay, we measured spike, S1, and nucleocapsid SARSCoV- 2 antigens in plasma collected at time of symptom assessment. Result(s): We examined 172 participants (50% men, 46% non-white, median age 46 years) who contributed 667 timepoints from 0.7 to 15.4 months following infection, at which 66% featured report of >=1 symptom. Sixty-one of 667 timepoints (9.1%) representing 24% of persons had >=1 detectable SARSCoV- 2 antigen. Among the 437 timepoints at which >=1 symptom was present, 9.8% had >=1 detectable antigen;this compares to 7.8% of timepoints at which symptoms were absent. In comparison to those without symptoms, individuals with several specific symptom complexes (gastrointestinal, musculoskeletal, and central neurologic) more commonly had detectable antigen (Figure). Hospitalization during acute COVID-19 was strongly related to antigen detection. Conclusion(s): Among a diverse group of SARS-CoV-2-infected persons in the post-acute phase of infection, SARS-CoV-2 antigen is detectable in plasma in both those with and without symptoms but more commonly in those with gastrointestinal, musculoskeletal, and central neurologic complaints. The findings indicate that antigen persists in at least some persons and suggest (but do not prove) that antigen is causally related to symptoms. That antigen is found in only a fraction of those with PASC indicates either that not all symptoms are driven by antigen, current plasma antigen detection is insensitive relative to tissue, or nominal PASC symptoms are sometimes unrelated to SARS-CoV-2. (Figure Presented).
ABSTRACT
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.
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Background: The biologic mechanisms underlying neurologic post-acute-sequelae of SARS-CoV-2 infection (PASC) are incompletely understood. We measured plasma markers of neuronal injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and inflammation among a cohort of people with prior confirmed SARS-CoV-2 infection at early and late recovery following the initial illness (defined as < and > 90 days since COVID-19 onset, respectively). We hypothesized that those experiencing persistent neurologic symptoms would have elevations in these markers. Methods: The primary clinical outcome was the presence of self-reported central nervous system (CNS) PASC symptoms during the late recovery timepoint. We compared fold-changes in marker values between those with and without CNS PASC symptoms using linear mixed effects models and examined relationships between neurologic and immunologic markers using rank linear correlations. Results: Of 121 individuals, 52 reported CNS PASC symptoms. During early recovery, those who went on to report CNS PASC symptoms had elevations in GFAP (1.3-fold higher mean ratio, 95% CI 1.04-1.63, p=0.02), but not NfL (1.06-fold higher mean ratio, 95% CI 0.89-1.26, p=0.54). During late recovery, neither GFAP nor NfL levels were elevated among those with CNS PASC symptoms. Although absolute levels of NfL did not differ, those who reported CNS PASC symptoms demonstrated a stronger downward trend over time in comparison to those who did not report CNS PASC symptoms (p=0.041). Those who went on to report CNS PASC also exhibited elevations in IL-6 (48% higher during early recovery and 38% higher during late recovery), MCP-1 (19% higher during early recovery), and TNF-alpha (19% higher during early recovery and 13% higher during late recovery). GFAP and NfL correlated with levels of several immune markers during early recovery (MCP-1, IL-6, TNF-a, IFN-g);these correlations were attenuated during late recovery. Conclusion: Self-reported neurologic symptoms present approximately four months following SARS-CoV-2 infection are associated with elevations in markers of neurologic injury and inflammation at early recovery timepoints, suggesting that early injury can result in long-term disease. The correlation of GFAP and NfL with markers of systemic immune activation suggests one possible mechanism that might contribute to these symptoms. Additional work will be needed to better characterize these processes and to identify interventions to prevent or treat this condition.
ABSTRACT
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.
ABSTRACT
Background: Although data are mixed, most cohorts show a similar or lower COVID-19 incidence among people living with HIV (PLWH) compared to the general population. However, incidence may be impacted by lower testing rates among vulnerable populations. We compared SARS-CoV-2 seroprevalence and IgG levels, and disease severity, among patients with and without HIV receiving care within a county hospital system over a three-month period. Methods: From August through October 2020, remnant serum samples were collected from all PLWH who underwent routine outpatient laboratory testing at San Francisco General Hospital which houses a large HIV clinic (Ward 86). Patients with HIV were matched on time of collection (same day) and age (+/- 5 years) to 1-2 adults without HIV. SARS-CoV-2 levels of IgG levels was quantified in serum using the Pylon IgG assay (100% specificity on internal validation). Seroprevalence was compared by HIV status via conditional logit models, adjusting for sex. For those with reactive results, IgG levels were compared by HIV status using log-transformed generalized estimating equations. Severe disease, assessed via chart review, was defined as requiring oxygen. Results: Among 1,411 individuals (46% PLWH), the median age was 58 (IQR: 49-65), 64% were men. COVID-19 seroprevalence was 3.1% among PLWH compared to 6.8% among people without HIV (adjusted odds ratio 0.41;95% confidence interval (CI): 0.25-0.68, p<0.001). Among those with reactive COVID-19 IgG results (n=72, 20 in PLWH);antibody levels were 47% lower among PLWH (95% CI: 19-65% lower;p=0.003;Figure);however, there was a trend towards higher disease severity among PLWH [15% (n=3) vs. 4% (n=2);p=0.13]. Conclusion: Both seroprevalence, and absolute SARS-CoV-2 IgG levels in those with reactive results, were lower among PLWH, within a time and agematched population of outpatients receiving routine laboratory testing in an urban hospital. PLWH may have had higher adherence to non-pharmaceutical interventions (NPIs) than those without HIV, leading to lower COVID-19 seroprevalence and, possibly, lower COVID-19 IgG levels if infected with a lower viral inoculum due to NPIs. Alternatively, PLWH may mount lower antibody responses to SARS-CoV-2, as has been demonstrated with hepatitis B and yellow fever vaccines. Further studies of COVID-19 susceptibility and immunity are needed among PLWH. Moreover, PLWH should be enrolled in SARS-CoV-2 vaccine studies or followed after vaccination to ensure they mount sufficient humoral responses.