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1.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-337494

ABSTRACT

Importance: Understanding the severity of post-vaccination COVID-19 breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations. Objective: Estimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection. Design, setting, and participants: The Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration consists of four US longitudinal cohorts from integrated health systems and academic centers. Adults (≥18 years old), in-care, fully vaccinated by June 30, 2021 with HIV, and matched PWoH (on date fully vaccinated, age group, race/ethnicity, and sex) were the source population. Those who experienced a post-vaccination SARS-CoV-2 breakthrough infection were eligible. Severe COVID-19 breakthrough illness was defined as hospitalization due to COVID-19. Discrete time proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals ([,]) of severe breakthrough illness by HIV status adjusting for demographics, COVID-19 vaccine type, and clinical factors. The proportion of patients requiring mechanical ventilation or died was compared by HIV status. Exposure: HIV infection Outcome: Severe COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. Results: Among 1,241 PWH and 2,408 PWoH with breakthrough infections, the cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs. 6.7%, respectively, risk difference=-0.67% [-2.58%, 1.23%]). The risk of severe breakthrough illness was 59% higher in PWH with CD4 counts <350 cells/mm3 compared with PWoH (aHR=1.59 [0.99, 2.46]). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 count increased the risk of severe breakthrough illness, while previous COVID-19 reduced the risk. Among all patients, 10% were mechanically ventilated and 8% died, with no difference by HIV status. Conclusions and Relevance: The risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. However, PWH with moderate and severe immune suppression had a higher risk of severe breakthrough infection. Recommendations for additional vaccine doses and risk-reduction strategies for PWH with moderate immune suppression may be warranted.

2.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333686

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities. SIGNIFICANCE: In this study we found that neutralizing antibody responses in COVID-19 convalescent individuals vary in magnitude but are durable and correlate well with RBD Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time, that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardio-metabolic co-morbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2.

3.
Open Forum Infectious Diseases ; 8(SUPPL 1):S33, 2021.
Article in English | EMBASE | ID: covidwho-1746794

ABSTRACT

Background. Little is known about how race and ethnicity, imperfect (albeit accessible) proxies for structural racism, impact COVID-19 incidence among people with HIV (PWH). We report the cumulative incidence and incidence rate ratios (IRR) for COVID-19 in a long-term multi-site cohort of PWH across the US Figure 1. Cumulative incidence of COVID-19 in the CNICS cohort Methods. We examined COVID-19 cumulative incidence and IRR among PWH in care between 3/1/2020 and 12/31/2020 at seven sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort. We define COVID-19 incident case as having a laboratory-confirmed (RT-PCR/Ag) SARS-CoV-2 positive result or diagnosis verified by chart review. Reinfections were excluded. Results are presented as monthly and quarterly cumulative incidence and IRR with 95% CI stratified by CD4 count, self-reported race/ethnicity, and site. Follow-up was censored on the earliest of diagnosis of COVID-19 disease, loss to follow up, or 12/31/2020 Results. Among 15,780 PWH in care in the CNICS cohort during the study period, 62% were non-white, with a median (IQR) age of 52 (IQR 40-59), 95% were on antiretroviral therapy, 17% had a CD4 count less than 350, and 6% less than 200. Overall, 651 PWH tested positive for COVID-19 for a cumulative incidence of 4.13%. COVID-19 cumulative incidence increased from 0.77% at the end of the first quarter to 4.12% by the end of December 2020. At the peak of the pandemic in December 2020, the cumulative incidence in Black PWH was 1.68 fold higher than in white PWH (p=.033) and 2.35 fold higher in Hispanics than in whites (P< .0001), figure 1. Similarly, the IRR for COVID-19 was 1.71 (95% CI 1.42-2.07) for Black and 2.40 (95% CI 1.91-3.01) for Hispanic PWH relative to white. Although there was variation across sites, reflecting geographic differences in pandemic waves and access to COVID-19 testing, overall individual trends remained the same. COVID-19 cumulative incidence was similar across CD4 cell count strata Conclusion. Our results suggest effects of structural racial disparities on COVID-19 incidence in this diverse population of PWH across the US, with higher and disproportionate rates of COVID-19 in Black and Hispanic PWH. Incidence estimates are conservative because testing was not uniform, and no systematic testing was conducted.

4.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296600

ABSTRACT

Importance: Recommendations for additional doses of COVID vaccine are restricted to people with HIV who have advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk post-vaccination among PWH is essential for informing vaccination guidelines. Objective: Estimate the risk of breakthrough infections among fully vaccinated people with (PWH) and without (PWoH) HIV in the US. Design setting and participants: The Corona-Infectious-Virus Epidemiology Team (CIVET)-II cohort collaboration consists of 4 longitudinal cohorts from integrated health systems and academic health centers. Each cohort identified individuals a18 years old, in-care, and fully vaccinated for COVID-19 through 30 June 2021. PWH were matched to PWoH on date fully vaccinated, age group, race/ethnicity, and sex at birth. Incidence rates per 1,000 person-years and cumulative incidence of breakthrough infections with 95% confidence intervals ([,]) were estimated by HIV status. Cox proportional hazards models estimated adjusted hazard ratios (aHR) of breakthrough infections by HIV status adjusting for demographic factors, prior COVID-19 illness, vaccine type (BNT162b2, [Pfizer], mRNA-1273 [Moderna], Jansen Ad26.COV2.S [J&J]), calendar time, and cohort. Risk factors for breakthroughs among PWH, were also investigated. Exposure: HIV infection. Outcome: COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after an individual was fully vaccinated. Results: Among 109,599 individuals (31,840 PWH and 77,759 PWoH), the rate of breakthrough infections was higher in PWH versus PWoH: 44 [41, 48] vs. 31 [29, 33] per 1,000 person-years. Cumulative incidence at 210 days after date fully vaccinated was low, albeit higher in PWH versus PWoH overall (2.8% versus 2.1%, log-rank p<0.001, risk difference=0.7% [0.4%, 1.0%]) and within each vaccine type. Breakthrough infection risk was 41% higher in PWH versus PWoH (aHR=1.41 [1.28, 1.56]). Among PWH, younger age (18-24 versus 45-54), history of COVID-19 prior to fully vaccinated date, and J&J vaccination (versus Pfizer) were associated with increased risk of breakthroughs. There was no association of breakthrough with HIV viral load suppression or CD4 count among PWH. Conclusions and Relevance: COVID-19 vaccination is effective against infection with SARS-CoV-2 strains circulating through 30 Sept 2021. PWH have an increased risk of breakthrough infections compared to PWoH. Recommendations for additional vaccine doses should be expanded to all PWH.

5.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296541

ABSTRACT

Objectives: To define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. Design: Observational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020. Methods: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. Results: Among 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200;95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count <350 (proxy for CD4 nadir), current low CD4/CD8 ratio, diabetes, and obesity. Conclusions: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.

6.
Topics in Antiviral Medicine ; 29(1):205, 2021.
Article in English | EMBASE | ID: covidwho-1250700

ABSTRACT

Background: COVID-19 outcomes among people with HIV (PWH) remain inconclusive. We characterized all cases of COVID-19 identified in a long-term multi-site cohort of PWH, as well as factors associated with increasing severity of COVID-19 during the early months of the COVID-19 pandemic. Methods: We examined all PWH with SARS-CoV-2 infection and COVID-19 disease identified from laboratory testing data (RT-PCR, antigen test results) and ICD-10 codes March-July 2020 from seven sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort. Cases were verified by medical record review. We evaluated predictors of increased disease severity, indicated by hospitalization. Relative risks were estimated using Poisson regression, adjusted for clinical and demographic characteristics using disease risk scores. Results: Among 13,862 PWH in care (20% female, median age 52 (IQR 40-59), 58% Black or Hispanic race/ethnicity), 198 COVID-19 cases were detected during the study period. A higher proportion of PWH with COVID-19 were female (27%), Black or Hispanic (76%), and had BMI ≥30 (45%). No significant differences in CD4+ count (current or lowest) were seen between PWH with and without COVID-19. We found evidence suggesting more unstable housing among COVID-19 cases compared to non-cases (14% vs. 9%). Among PWH with COVID-19, 38 (19%) were hospitalized, 10 (5%) required intensive care, 8 (4%) received invasive mechanical ventilation, and 4 (2%) died. Hospitalization among PWH with COVID-19 was associated with: CD4+ count ≤350 (aRR 1.77;95% CI 1.05, 2.98);age ≥60 (aRR 2.0;95%CI 1.13, 3.54);pre-existing kidney disease with eGFR <60 (aRR 1.76;95% CI 0.99, 3.13);and BMI ≥30 (aRR 1.96;95% CI 1.02, 3.78) (Table). Conclusion: The population frequency of COVID-19 detected in PWH was 1.4%, likely an underestimate of the true frequency of SARS-CoV-2 infection and COVID-19 disease due to evolving testing availability and access over time. A higher proportion of PWH with COVID-19 were Black or Hispanic, in excess of the overrepresentation of people of color with HIV compared to the general population. PWH with decreased eGFR, low CD4+ count, and obesity had greater risk of more severe COVID-19 disease. Our results highlight disparities in risk of COVID-19 acquisition among PWH in the US and indicate additional vigilance in screening and monitoring of COVID-19 among PWH with these characteristics. The expected accrual of additional COVID-19 cases will allow more precise evaluation of the impact of comorbidities. (Figure Presented).

7.
Topics in Antiviral Medicine ; 29(1):241-242, 2021.
Article in English | EMBASE | ID: covidwho-1250573

ABSTRACT

Background: It is not known if people with HIV (PWH) in the United States (US) have different access to SARS-CoV-2 RT-PCR (COVID-19) testing, or positivity proportions (among those tested), than people without HIV (PWOH). We describe COVID-19 testing and positivity proportions in 6 large geographically and demographically diverse cohorts of PWH and PWOH. Methods: The Corona-Infectious-Virus Epidemiology Team (CIVET) is comprised of five COVID-19 clinical cohorts within a health system (Kaiser Permanente Northern California, Oakland, CA;Kaiser Permanente Mid-Atlantic States, Rockville, MD;University of North Carolina Health, Chapel Hill, NC;Vanderbilt University Medical Center, Nashville, TN;Veterans Aging Cohort Study) and one established classical HIV cohort (MACS/WIHS Combined Cohort Study). Each participating cohort is restricted to individuals who were alive and “in-cohort” in 2020 (definitions of which were operationalized to fit the structure of each cohort). We calculated the percentage of patients in-cohort who were COVID-19 tested, and the proportion COVID-19 positive monthly, by HIV status, from March 1 to August 31, 2020. We report findings from the classical cohort separately because results are based on self-reported information. Results: In the 5 clinical cohorts, PWH ranged from N=2,515 to 31,040, and N=77,019 to 3,710,360 PWOH. Over the 6 month study period, the percentage of PWH who were tested for COVID-19 (13.5%-21.2%) was slightly higher than PWOH (10.8%-14.3%) in each of the cohorts (p-values in each cohort <0.001). However, among those tested, the percentage of patients with positive COVID-19 tests was similar regardless of HIV status (Figure). In the classical cohort that contributed self-reported testing and positive information (PWH N=2,222;PWOH N=1,417), the proportion tested was similar by HIV status (PWH 38.1% vs. PWOH 37.4%), but PWH had a greater positivity proportion (9.0%) compared with PWOH (5.3%, p-value=0.012). Conclusion: Although PWH had higher testing rates compared with PWOH, we did not find evidence of increased positivity among those tested in 5 clinical cohorts with large diverse populations across the US. We will continue to monitor testing, positivity, and COVID-19 related health outcomes in PWH and PWOH using our multiple data sources and leveraging the expertise of established longitudinal cohort studies in the CIVETS collaboration.

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