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COVID-19 Outcomes Among Persons Living With or Without Diagnosed HIV Infection in New York State
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Feb 3 2021
Conclusions
Although the mechanisms underpinning increased risk are not fully understood, the intersection of HIV and COVID-19 has multiple implications. Because HIV infection is a marker for, and may play a direct role in, more severe COVID-19 outcomes, persons living with diagnosed HIV (with any CD4 count) may warrant recategorization from "might be at increased risk" to "increased risk" in the Centers for Disease Control and Prevention's underlying medical conditions list.5 This change may lead to higher prioritization of persons living with diagnosed HIV for receipt of the COVID-19 vaccine, per national and state allocation plans.48,49 Finally, a syndemic association between these infections may act multiplicatively on affected persons and communities, which are more likely to involve persons of color and urban areas.50 Our findings present an opportunity to address health equity with regard to HIV and COVID-19 through a combination of prevention and treatment approaches.51
After adjustment, the standardized mortality ratio among persons living with diagnosed HIV vs persons living without diagnosed HIV was 1.23, per population (95% CI, 1.07-1.40), and was 1.79 (95% CI, 1.56-2.05) among those diagnosed.
We found that persons living with diagnosed HIV were significantly more likely than persons living without diagnosed HIV to be hospitalized with COVID-19, overall and among individuals with a diagnosis of COVID-19, suggesting higher rates of severe disease among persons living with diagnosed HIV requiring hospitalization. Hospitalization rates among persons living with diagnosed HIV were higher among those without viral suppression and those with lower CD4 counts, suggesting that more advanced disease may increase COVID-19 severity to the point that hospitalization is required. Our finding that higher hospitalization rates among persons living with diagnosed HIV compared with persons living without diagnosed HIV persisted among the subset of persons living with diagnosed HIV who had high CD4 counts suggests that additional factors may be associated with elevated hospitalization rates among persons living with diagnosed HIV, including other comorbidities, systemic stress of chronic infection, and social determinants of COVID-19 severity.
There were 490 deaths among persons living with diagnosed HIV from March 1 to June 15, 2019 (Mark Rosenthal, MSPH, NYS Department of Health, email, October 27, 2020). Against this backdrop, the 207 COVID-19–specific hospital deaths in our study represent a 42% addition to anticipated deaths during this same interval in 2020. Further analyses refining this estimate are needed. Higher mortality among persons living with diagnosed HIV was reported in a large population cohort study of health care attendees in South Africa,13 in cohorts of hospitalized patients in London14 and NYC,15 and in a study of persons living with diagnosed HIV receiving antiretroviral therapy in 60 Spanish hospitals.33 Contrary findings have been reported in an NYC study comparing 88 hospitalized persons living with diagnosed HIV with COVID-19 with a matched control group of persons living without diagnosed HIV.4
The only significant factor associated with in-hospital mortality among hospitalized persons living with diagnosed HIV was age, with those aged 40 years or older being 3 to 4 times more likely to experience in-hospital death. Given the well-established findings on elevated mortality by increasing age regardless of HIV status,13,33,40 this finding likely reflects an elevated risk of COVID-19 severity–enhancing comorbidities, including diabetes, hypertension, and chronic lung and cardiovascular disease, among older adults. Also, as reported in the literature, we found that persons living with diagnosed HIV hospitalized with and dying from COVID-19 were younger than persons living without diagnosed HIV.12,41 This finding may lend support to the notion that HIV infection can accelerate biological aging.42,43
Although non-Hispanic Black persons living with diagnosed HIV and Hispanic persons living with diagnosed HIV were more likely to receive a diagnosis of COVID-19 than non-Hispanic White persons living with diagnosed HIV, they were not more likely to be hospitalized once diagnosed or to die once hospitalized. This finding is partially consistent with COVID-19 studies finding racial/ethnic disparity present in hospitalization rates but not in mortality.19,44-46 Finally, despite RRs in the expected direction, CD4 count was not significantly associated with in-hospital death. This finding is incongruent with at least 2 studies finding that CD4 counts less than 200 cells/mm3 were significantly associated with decreased survival among hospitalized persons living with diagnosed HIV.13,33
COVID-19 Outcomes Among Persons Living With or Without Diagnosed HIV Infection in New York State
Feb 3 2021 - JAMA Netw. Open - JamesM. Tesoriero, PhD; Carol-Ann E. Swain, PhD; Jennifer L. Pierce, BS; Lucila Zamboni, PhD; MengWu, PhD; David R. Holtgrave, PhD; Charles J. Gonzalez, MD;
Tomoko Udo, PhD; Johanne E. Morne, MS; Rachel Hart-Malloy, PhD; Deepa T. Rajulu, MS; Shu-Yin John Leung, MA; Eli S. Rosenberg, PhD
Key Points
Question Is there an association between prior diagnosis of HIV infection and coronavirus disease 2019 (COVID-19) diagnosis, hospitalization, and in-hospital death among residents of New York State?
Findings In a cohort study of linked statewide HIV diagnosis, COVID-19 laboratory diagnosis, and hospitalization databases, persons living with an HIV diagnosis were more likely to receive a diagnosis of, be hospitalized with, and die in-hospital with COVID-19 compared with those not living with an HIV diagnosis. After demographic adjustment, COVID-19 hospitalization remained significantly elevated for individuals with an HIV diagnosis and was associated with elevated mortality.
Meaning Persons living with an HIV diagnosis experienced poorer COVID-related outcomes (principally, higher rates of severe disease requiring hospitalization) relative to those without an HIV diagnosis.
Abstract
Importance New York State has been an epicenter for both the US coronavirus disease 2019 (COVID-19) and HIV/AIDS epidemics. Persons living with diagnosed HIV may be more prone to COVID-19 infection and severe outcomes, yet few studies have assessed this possibility at a population level.
Objective To evaluate the association between HIV diagnosis and COVID-19 diagnosis, hospitalization, and in-hospital death in New York State.
Design, Setting, and Participants This cohort study, conducted in New York State, including New York City, between March 1 and June 15, 2020, matched data from HIV surveillance, COVID-19 laboratory-confirmed diagnoses, and hospitalization databases to provide a full population-level comparison of COVID-19 outcomes between persons living with diagnosed HIV and persons living without diagnosed HIV.
Exposures Diagnosis of HIV infection through December 31, 2019.
Main Outcomes and Measures The main outcomes were COVID-19 diagnosis, hospitalization, and in-hospital death. COVID-19 diagnoses, hospitalizations, and in-hospital death rates comparing persons living with diagnosed HIV with persons living without dianosed HIV were computed, with unadjusted rate ratios and indirect standardized rate ratios (sRR), adjusting for sex, age, and region. Adjusted rate ratios (aRRs) for outcomes specific to persons living with diagnosed HIV were assessed by age, sex, region, race/ethnicity, transmission risk, and CD4+ T-cell count–defined HIV disease stage, using Poisson regression models.
Results A total of 2988 persons living with diagnosed HIV (2109 men [70.6%]; 2409 living in New York City [80.6%]; mean [SD] age, 54.0 [13.3] years) received a diagnosis of COVID-19. Of these persons living with diagnosed HIV, 896 were hospitalized and 207 died in the hospital through June 15, 2020. After standardization, persons living with diagnosed HIV and persons living without diagnosed HIV had similar diagnosis rates (sRR, 0.94 [95% CI, 0.91-0.97]), but persons living with diagnosed HIV were hospitalized more than persons living without diagnosed HIV, per population (sRR, 1.38 [95% CI, 1.29-1.47]) and among those diagnosed (sRR, 1.47 [95% CI, 1.37-1.56]). Elevated mortality among persons living with diagnosed HIV was observed per population (sRR, 1.23 [95% CI, 1.07-1.40]) and among those diagnosed (sRR, 1.30 [95% CI, 1.13-1.48]) but not among those hospitalized (sRR, 0.96 [95% CI, 0.83-1.09]). Among persons living with diagnosed HIV, non-Hispanic Black individuals (aRR, 1.59 [95% CI, 1.40-1.81]) and Hispanic individuals (aRR, 2.08 [95% CI, 1.83-2.37]) were more likely to receive a diagnosis of COVID-19 than White individuals, but they were not more likely to be hospitalized once they received a diagnosis or to die once hospitalized. Hospitalization risk increased with disease progression to HIV stage 2 (aRR, 1.29 [95% CI, 1.11-1.49]) and stage 3 (aRR, 1.69 [95% CI, 1.38-2.07]) relative to stage 1.
Conclusions and Relevance In this cohort study, persons living with diagnosed HIV experienced poorer COVID-related outcomes relative to persons living without diagnosed HIV; Previous HIV diagnosis was associated with higher rates of severe disease requiring hospitalization, and hospitalization risk increased with progression of HIV disease stage.
Results
From March 1 to June 7, 2020, among 108 062 persons living with diagnosed HIV in NYS, 2988 (2109 men [70.6%]; 2409 living in New York City [80.6%]; mean [SD] age, 54.0 [13.3] years) received a diagnosis of COVID-19 at a rate of 27.7 per 1000, which was higher than among persons living without diagnosed HIV (rate, 19.4 per 1000; RR, 1.43 [95% CI, 1.38-1.48]) (Table 1). Similarly, elevated rates of COVID-19 were observed across age categories (except for persons aged 40-59 years), sex, and region of residence at HIV diagnosis. Standardization for these factors yielded an overall adjusted diagnosis rate ratio (sRR) of 0.94 (95% CI, 0.91-0.97), comparing persons living with diagnosed HIV with persons living without diagnosed HIV (Figure). Standardized RRs were significantly above 1.0 in regions outside of NYC but lower in NYC (eTable 1 in the Supplement).
Population-level rates of COVID-19 hospitalization were significantly elevated among persons living with diagnosed HIV (8.29 per 1000) vs persons living without diagnosed HIV (3.15 per 1000; RR, 2.61 [95% CI, 2.45-2.79]) and consistently so across age, sex, and geography (Table 1). In unadjusted analyses, relative hospitalization for persons living with diagnosed HIV vs persons living without diagnosed HIV was highest for persons younger than 40 years (RR, 3.08 [95% CI, 2.40-3.95]), women (RR, 3.19 [95% CI, 2.82-3.59]), and those living in the rest of NYS (RR, 3.51 [95% CI, 2.37-5.20]). After standardization, the disparity in hospitalization between persons living with diagnosed HIV and persons living without diagnosed HIV decreased but remained significantly elevated, per population (sRR, 1.38 [95% CI, 1.29-1.47]), and among those diagnosed with COVID-19 (sRR, 1.47 [95% CI, 1.38-1.56]).
Overall, 207 persons living with diagnosed HIV (rate, 1.92 per 1000) had a COVID-19 diagnosis and died in the hospital at a higher rate than persons living without diagnosed HIV (RR, 2.55 [95% CI, 2.22-2.93]) (Table 1). Unadjusted per-population relative mortality among persons living with diagnosed HIV vs persons living without diagnosed HIV was highest among persons younger than 40 years (RR, 5.74 [95% CI, 2.14-15.42]), women (RR, 3.74 [95% CI, 2.94-4.77]), and residents of Long Island (RR, 2.42 [95% CI, 1.40-4.17]). After adjustment, the standardized mortality ratio among persons living with diagnosed HIV vs persons living without diagnosed HIV was 1.23, per population (95% CI, 1.07-1.40), and was 1.79 (95% CI, 1.56-2.05) among those diagnosed.
The conditional rates per previous outcomes stage for persons living with diagnosed HIV vs persons living without diagnosed HIV are summarized in the Figure, alongside population-level rates, and in eTable 2 in the Supplement. Among those with a diagnosis of COVID-19, nearly one-third (299.87 per 1000) of persons living with diagnosed HIV were hospitalized, a higher rate than among persons living without diagnosed HIV (RR, 1.83 [95% CI, 1.72-1.96]). Among those hospitalized with COVID-19, no differences were seen in in-hospital death between persons living with diagnosed HIV and persons living without diagnosed HIV (RR, 0.98 [95% CI, 0.85-1.12]; sRR, 0.96 [95% CI, 0.83-1.09]). Despite the lack of significant difference in adjusted in-hospital mortality conditional on hospitalization, the higher levels of hospitalization for persons living with diagnosed HIV underpinned the significantly higher mortality rates per person and per diagnosis (case fatality rate, 69.28 per 1000 vs 38.70 per 1000; sRR, 1.30 [95% CI, 1.13-1.43]).
Among persons living with diagnosed HIV, in bivariate analyses, COVID-19 diagnosis was associated with all factors examined, except for sex (Table 2).25 In an adjusted model, persons living with diagnosed HIV of older age, not white non-Hispanic race/ethnicity, and living in the regions of metropolitan NYC were significantly more likely to receive a diagnosis of COVID-19. Among persons living with diagnosed HIV, non-Hispanic Black individuals (aRR, 1.59 [95% CI, 1.40-1.81]) and Hispanic individuals (aRR, 2.08 [95% CI, 1.83-2.37]) were more likely to receive a diagnosis of COVID-19 than White individuals, but they were not more likely to be hospitalized once they received a diagnosis or to die once hospitalized. No significant differences were observed between the main HIV transmission risk groups. After controlling for these factors, we found that having stage 3 HIV infection (vs stage 1: aRR, 1.22 [95% CI, 1.07-1.38]) was associated with increased rate of COVID-19 diagnosis.
On further examination of the risk factors for hospitalization among persons living with diagnosed HIV and with diagnosed COVID-19, in adjusted analyses, older age and region, but not race and not ethnicity or transmission risk, were associated with hospitalization (Table 2).25 Relative to stage 1 infection, there was a gradient of increased hospitalization risk across stage 2 infection (aRR, 1.29 [95% CI, 1.11-1.49]) and stage 3 infection (aRR, 1.69 [95% CI, 1.38-2.07]). Among those hospitalized, only older age was associated with in-hospital death.
To probe the role of HIV stage in increasing hospitalization risk for persons living with diagnosed HIV vs persons living without diagnosed HIV, we conducted the per-person hospitalization standardized rate analysis by stage of HIV disease. Relative to persons living without diagnosed HIV, hospitalization risk was elevated for those with HIV stage 1 infection (sRR, 1.19 [95% CI, 1.08-1.30]), stage 2 infection (sRR, 1.60 [95% CI, 1.42-1.78]), and stage 3 infection (sRR, 2.66 [95% CI, 2.20-3.13])
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