The Association Between Comorbidities and Coronavirus Disease 2019 Hospitalization Among People With HIV Differs by age

Caitlin A. Moran; Nora T. Oliver; Brittany Szabo; Lauren F. Collins; Minh Ly T. Nguyen; N. Sarita Shah; Abeer Moanna; Jonathan A. Colasanti; Valeria D. Cantos; Wendy S. Armstrong; Anandi N. Sheth; Ighovwerha Ofotokun; Colleen F. Kelley; Vincent C. Marconi; Cecile D. Lahiri

Disclosures

AIDS. 2023;37(1):71-81.

Abstract and Introduction

Abstract

Objectives: To determine whether factors associated with coronavirus disease 2019 (COVID-19) hospitalization among people with HIV (PWH) differ by age stratum.

Design: Retrospective cohort study.

Methods: All adult PWH with a positive SARS-CoV-2 PCR in a public safety-net health system between 1 March 2020 and 28 February 2021 and a Veterans Affairs Medical Center between 1 1 March 2020 and 15 November 2020 in Atlanta, Georgia were included. We performed multivariable logistic regression to determine demographic and clinical factors associated with COVID-19 hospitalization overall and stratified by age less than 50 and at least 50 years.

Results: Three hundred and sixty-five PWH (mean age 49 years, 74% cisgender male, 82% black) were included. Ninety-six percent were on antiretroviral therapy (ART), 87% had CD4⁺ T-cell count at least 200 cells/μl, and 89% had HIV-1 RNA less than 200 copies/ml. Overall, age [adjusted odds ratio (aOR) 95% confidence interval (CI) 1.07 (1.04–1.10)], later date of SARS-CoV-2 infection [aOR 0.997 (0.995–1.00)], heart disease [aOR 2.27 (1.06–4.85)], and history of hepatitis C virus (HCV) [aOR 2.59 (1.13–5.89)] were associated with COVID-19 hospitalization. Age-adjusted comorbidity burden was associated with 30% increased risk of hospitalization [aOR 1.30 (1.11–1.54)]. Among 168 PWH less than 50 years old, older age [aOR 1.09 (1.01–1.18)] and no ART use [aOR 40.26 (4.12–393.62)] were associated with hospitalization; age-adjusted comorbidity burden was not (P = 0.25). Among 197 PWH at least 50, older age [aOR 1.10 (1.04–1.16)], heart disease [aOR 2.45 (1.04–5.77)], history of HCV [aOR 3.52 (1.29–9.60)], and age-adjusted comorbidity burden [aOR 1.36 (1.12–1.66)] were associated with hospitalization.

Conclusion: Comorbidity burden is more strongly associated with COVID-19 hospitalization among older, rather than younger, PWH. These findings may have important implications for risk-stratifying COVID-19 therapies and booster recommendations in PWH.

Introduction

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in late December 2019, it has been well established that advanced age, comorbidity burden, and immunosuppression are risk factors for severe COVID-19.^[1,2] However, for people with HIV (PWH), risk factors for severe COVID-19 remain unclear. PWH have been shown to be at increased risk of severe COVID-19 including hospitalization^[3,4] and death^[5–8] after controlling for age and sex, but reasons for this elevated risk are likely multifactorial. There is mounting evidence, mostly from cohorts of PWH with well controlled HIV in North America and western Europe that an increased comorbidity burden plays a large role in severe COVID-19 risk among PWH.^[9,10] Other larger studies from similar settings also implicate HIV-specific parameters including CD4⁺ T-cell count, CD4⁺/CD8⁺ ratio, HIV-1 RNA viremia, and specific antiretroviral therapy (ART) use.^[7,11–13] These data suggest that, while age and comorbidity burden are important contributors to COVID-19 severity among PWH, HIV-related factors, particularly CD4⁺ T-cell count, may also play a role.

Most of the available data do not address specific risk factors for COVID-19 hospitalization among PWH by age group. If differences by age group exist, they may have important implications for COVID-19 treatment and prevention guidelines. One cohort study conducted in the United Kingdom through June 2020 found that COVID-19 mortality was greater among PWH age less than 60 years compared with people without HIV in the same age group.^[8] Current COVID-19 treatment guidelines consider age at least 65 years to be a risk factor for severe disease,^[14] but this age cutoff may need to be reconsidered in PWH. Stratification at age 50 was chosen a priori based on evidence of increased risk for multimorbidity in PWH at that age.^[15] Previous work has shown that PWH experience accelerated aging and age-related comorbidities at earlier ages compared with the general population,^[16,17] and risk of these comorbidities appears to increase after age 50, often sooner than in the general population.^[15,16] Therefore, we sought to determine risk factors for hospitalization for COVID-19 among PWH overall and stratified by age less than 50 years and at least 50 years.

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AIDS. 2023;37(1):71-81. © 2023 Lippincott Williams & Wilkins
Lippincott Williams & Wilkins

Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Baseline characteristics of people with HIV by coronavirus disease 2019 hospitalization status for the entire cohort and by age strata.
Variable	Entire cohort (n = 365)			Age <50 (n = 168)			Age ≥50 (n = 197)
Variable	Not hospitalized (n = 258)	Hospitalized (n = 106)	P value	Not hospitalized (n = 145)	Hospitalized (n = 23)	P value	Not hospitalized (n = 113)	Hospitalized (n = 83)	P value
Demographic variables
Age [mean (SD)]	45.1 (12.9)	57.0 (11.1)	<0.001	35.6 (8.3)	40.4 (7.7)	0.01	57.1 (5.6)	61.5 (6.6)	<0.001
Gender [n (%)]			0.17			0.13			0.71
Cis-male	195 (76)	72 (68)		110 (76)	14 (61)		85 (75)	58 (70)
Cis-female	57 (22)	33 (31)		30 (21)	9 (39)		27 (24)	24 (29)
Trans-female	5 (2)	1 (1)		4 (3)	0 (0)		1 (1)	1 (1)
Race/ethnicity [n (%)]			0.84			0.66			0.82
Black	209 (81)	88 (83)		120 (83)	21 (91)		89 (79)	67 (81)
Hispanic/Latinx	27 (10)	11 (10)		17 (12)	2 (9)		10 (9)	9 (11)
White	16 (6)	6 (6)		4 (3)	0 (0)		12 (11)	6 (7)
Other	6 (2)	1 (1)		4 (3)	0 (0)		2 (2)	1 (1)
Site [n (%)]			0.003			0.02			0.13
Grady	234 (91)	84 (79)		135 (93)	18 (78)		99 (88)	66 (80)
AVAMC	24 (9)	22 (21)		10 (7)	5 (22)		14 (12)	17 (20)
Current smoker [n (%)]	71 (28)	19 (18)	0.054	39 (27)	5 (22)	0.60	32 (28)	14 (17)	0.06
Alcohol abuse [n (%)]	22 (9)	7 (7)	0.54	10 (7)	2 (9)	0.67	12 (11)	5 (6)	0.26
Illicit drug use [n (%)]	21 (8)	10 (9)	0.69	10 (7)	5 (22)	0.04	11 (10)	5 (6)	0.35
HIV-related clinical variables
CD4 ⁺ cells/μl, mean (SD)	519 (298)	507 (307)	0.73	550.3 (336.3)	500.8 (410.3)	0.53	478.7 (234.5)	508.7 (275.1)	0.41
CD4 ⁺ ≥200 cells/μl, n(%)	223 (87)	92 (87)	0.86	122 (85)	17 (74)	0.22	101 (90)	75 (90)	0.97
HIV-1 RNA <200 copies/ml [n (%)]	227 (89)	95 (90)	0.94	124 (87)	18 (78)	0.34	103 (93)	77 (93)	0.99
ART [n (%)]	250 (97)	99 (93)	0.08	142 (99)	20 (87)	0.02	108 (96)	79 (95)	1.00
TDF [n (%)]	14 (6)	6 (6)	0.94	9 (6)	1 (4)	1.00	5 (4)	5 (6)	0.75
PI [n (%)]	32 (13)	18 (17)	0.26	18 (13)	6 (26)	0.11	14 (13)	12 (15)	0.67
INSTI [n (%)]	222 (87)	85 (81)	0.11	125 (88)	17 (74)	0.10	97 (87)	68 (83)	0.48
Comorbidities
Hypertension [n (%)]	101 (39)	63 (59)	0.0004	41 (28)	7 (30)	0.83	60 (53)	56 (67)	0.04
Dyslipidemia [n (%)]	62 (24)	46 (43)	0.0002	22 (15)	6 (26)	0.19	40 (35)	40 (48)	0.07
Diabetes mellitus [n (%)]	40 (16)	39 (37)	<0.001	13 (9)	5 (22)	0.08	27 (24)	34 (41)	0.01
Heart disease [n (%)]	18 (7)	25 (24)	<0.001	6 (4)	2 (9)	0.30	12 (11)	23 (28)	0.002
Chronic lung disease [n (%)]	22 (9)	16 (15)	0.06	8 (6)	2 (9)	0.63	14 (12)	14 (17)	0.38
Obesity [n (%)]	82 (33)	43 (41)	0.15	44 (32)	9 (39)	0.48	38 (34)	34 (41)	0.29
BMI [mean (SD)]	28.5 (6.6)	28.8 (7.3)	0.75	28.3 (6.8)	29.2 (10.6)	0.71	28.7 (6.2)	28.6 (6.1)	0.92
Chronic kidney disease [n (%)]	30 (12)	26 (25)	0.002	11 (8)	2 (9)	0.69	19 (17)	24 (30)	0.08
History of HBV [n (%)]	13 (5)	1 (1)	0.06	5 (3)	0 (0)	1.00	8 (7)	1 (1)	0.052
History of HCV [n (%)]	19 (7)	18 (17)	0.006	8 (6)	1 (4)	1.00	11 (10)	17 (20)	0.03
HCV viremia [n (%)]	10 (4)	6 (6)	0.46	4 (3)	0 (0)	1.00	6 (5)	6 (7)	0.58
Malignancy [n (%)]	13 (5)	12 (11)	0.03	8 (6)	4 (17)	0.06	5 (4)	8 (10)	0.15
Solid organ transplant [n (%)]	1 (<1)	2 (2)	0.15	0 (0)	1 (4)	0.14	1 (1)	1 (1)	1.00
Comorbidity burden [median, (q1, q3)]	1 (0,2)	3 (1,4)	<0.001	1 (2,6)	2 (3,5)	0.054	2 (1,3)	3 (2,4)	<0.001

ART classes are not mutually exclusive. ART, antiretroviral therapy; AVAMC, Atlanta Veterans Affairs Medical Center; COVID-19, coronavirus disease 2019; HBV, hepatitis B virus; HCV, hepatitis C virus; INSTI, integrase strand transfer inhibitor; PI, protease inhibitor; PWH, people with HIV; q1,q3, first quartile, third quartile SD, standard deviation; TDF, tenofovir disoproxil fumarate.

Table 2. Outcomes of coronavirus disease 2019 among hospitalized people with HIV, overall and by age strata.
Outcome	Overall	Age <50	Age ≥50	P value
Overall mortality^a (n = 365) [n (%)]	14 (4)	2 (1)	12 (6)	0.02
In-hospital mortality (n = 106) [n (%)]	13 (12)	2 (9)	11 (13)	0.56
Maximum O2 requirement [n (%)]				0.54
Room air	47 (44)	13 (57)	34 (41)
Nasal cannula	33 (31)	5 (22)	28 (34)
HFNC/NRB	13 (12)	2 (9)	11 (13)
IMV/ECMO	13 (12)	3 (13)	10 (12)
LOS (days) [median (q1, q3)]	6 (4, 12)	6 (4, 8)	6 (4, 13)	0.17
Discharge disposition				0.68
Home	74 (80)	18 (90)	56 (77)
SNF/SAR	13 (14)	2 (10)	11 (15)
Other acute facility	2 (2)	0 (0)	2 (3)
Hospice	2 (2)	0 (0)	2 (3)
Other	2 (2)	0 (0)	2 (3)
Treatment
Clinical trial^b [n (%)]	5 (5)	0 (0)	5 (6)	0.23
ACTT1	2 (2)	0 (0)	2 (2)	0.45
ACTT2	2 (2)	0 (0)	2 (2)	0.45
ACTT4	1 (1)	0 (0)	1 (1)	0.60
Sarilumab vs. placebo	1 (1)	0 (0)	1 (1)	0.60
Remdesivir [n (%)]	42 (40)	6 (26)	36 (43)	0.13
Dexamethasone [n (%)]	45 (42)	8 (35)	37 (45)	0.40
Baricitinib [n (%)]	1 (1)	0 (0)	1 (1)	0.60
Tocilizumab [n (%)]	1 (1)	0 (0)	1 (1)	0.60
Hydroxychloroquine [n (%)]	8 (8)	4 (17)	4 (5)	0.04
Azithromycin [n (%)]	11 (10)	2 (9)	9 (11)	0.77
Monoclonal antibodies^b [n (%)]	18 (5)	4 (2)	14 (7)	0.04

ACTT, adaptive COVID-19 treatment trial; ECMO, extracorporeal membrane oxygenation; HFNC, high-flow nasal cannula; IMV, invasive mechanical ventilation; LOS, length of stay; NRB, nonrebreather; SAR, subacute rehabilitation; SNF, skilled nursing facility.
^aIncludes inpatients and outpatients.
^bACTT1, remdesivir vs. placebo; ACTT2, remdesivir + baricitinib vs. remdesivir + placebo; ACTT4, remdesivir + baricitinib vs. remdesivir + dexamethasone.

Table 3. Unadjusted and adjusted odds of coronavirus disease 2019 hospitalization for people with HIV in the entire cohort.
Variable	OR (95% CI)	P value	aOR (95% CI)	P value
Demographic variables
Age	1.09 (1.06–1.11)	<0.001	1.07 (1.04–1.10)	<0.001
Gender		0.18
Cisgender male	Referent
Cisgender female	1.57 (0.95–2.60)
Transgender female	0.54 (0.06–4.72)
Race/ethnicity		0.86
White	Referent
Black	1.12 (0.43–2.96)
Hispanic/Latinx	1.09 (0.34–3.51)
Other	0.44 (0.04–4.50)
Date of SARS-CoV-2	0.997 (0.995–0.999)	0.02	0.997 (0.995–1.00)	0.049
Site at AVAMC	2.55 (1.36–4.80)	0.004	1.54 (0.71–3.34)	0.28
Current smoking	0.58 (0.33–1.01)	0.056
Alcohol abuse	0.76 (0.31–1.83)	0.54
Illicit drug use	1.17 (0.53–2.59)	0.69
HIV-related clinical variables
CD4⁺ count <200 cells/μl	1.06 (0.54–2.08)	0.86
HIV-1 RNA ≥200 copies/ml	0.97 (0.46–2.04)	0.94
ART (no vs. yes)	2.53 (0.86–7.38)	0.09
TDF	1.04 (0.39–2.78)	0.94
Protease inhibitor	1.44 (0.77–2.69)	0.26
INSTI	0.61 (0.33–1.13)	0.12
Comorbidities
Hypertension	2.28 (1.44–3.61)	<0.001	0.93 (0.51–1.69)	0.82
Dyslipidaemia	2.42 (1.50–3.91)	<0.001	1.00 (0.53–1.89)	>0.99
Diabetes mellitus	3.17 (1.89–5.33)	<0.001	1.90 (0.99–3.64)	0.052
Heart disease	4.12 (2.14–7.93)	<0.001	2.27 (1.06–4.85)	0.03
Chronic lung disease	1.91 (0.96–3.80)	0.07
Obesity	1.42 (0.89–2.26)	0.15
BMI	1.01 (0.97–1.04)	0.75
Chronic kidney disease	2.47 (1.38–4.43)	0.002	1.36 (0.68–2.72)	0.39
History of HBV	0.18 (0.02–1.39)	0.10
History of HCV	2.56 (1.29–5.11)	0.008	2.59 (1.13–5.89)	0.02
HCV viremia	1.48 (0.53–4.19)	0.46
Malignancy	2.41 (1.06–5.46)	0.04	2.26 (0.85–5.99)	0.10
Solid organ transplant	4.94 (0.44–55.09)	0.19
Comorbidity burden^a	1.58 (1.36–1.83)	<0.001	1.31 (1.11–1.54)	0.001

Multivariable model adjusted for age, date of SARS-CoV-2 infection, site, hypertension, dyslipidaemia, diabetes mellitus, heart disease, chronic kidney disease, chronic HCV, and malignancy. aOR, adjusted odds ratio; ART, antiretroviral therapy; AVAMC, Atlanta Veterans Affairs Medical Center; CI, confidence interval; HBV, hepatitis B virus; HCV, hepatitis C virus; INSTI, integrase strand transfer inhibitor; OR, odds ratio; PWH, people with HIV; TDF, tenofovir disoproxil fumarate.
^aAdjusted for age only.

Table 4. Unadjusted and adjusted odds of coronavirus disease 2019 hospitalization for people with HIV stratified by age.
Variable	Age <50 (n = 168)				Age ≥50 (n = 197)
Variable	OR (95% CI)	P value	aOR (95% CI)	P value	OR (95% CI)	P value	aOR (95% CI)	P value
Demographic variables
Age	1.08 (1.02–1.15)	0.01	1.09 (1.01–1.18)	0.04	1.12 (1.07–1.18)	<0.001	1.10 (1.04–1.16)	0.001
Cis/trans-female vs. cis-male	2.08 (0.83–5.237)	0.12			1.31 (0.70–2.47)	0.41
All other race/ethnicity vs. black	0.46 (0.10–2.08)	0.31			0.89 (0.44–1.80)	0.74
Date of SARS-CoV-2	0.995 (0.990–1.00)	0.03	0.995 (0.009–1.001)	0.12	0.997 (0.994–1.00)	0.046	0.998 (0.994–1.001)	0.16
Site at AVAMC vs. Grady	3.75 (1.15–12.22)	0.03	1.50 (0.34–6.67)	0.59	1.82 (0.84–3.95)	0.13	1.40 (0.52–3.73)	0.51
Current smoking	0.76 (0.26–2.17)	0.60			0.51 (0.25–1.04)	0.06
Alcohol abuse	1.29 (0.26–6.28)	0.76			0.54 (0.18–1.60)	0.26
Illicit drug use	3.75 (1.15–12.22)	0.03	3.86 (0.87–17.25)	0.08	0.59 (0.20–1.78)	0.35	0.45 (0.12–1.62)	0.22
HIV-related clinical variables
CD4⁺ count <200 cells/μl	2.05 (0.73–5.80)	0.18			0.98 (0.38–2.55)	0.97
HIV RNA ≥200 copies/ml	1.81 (0.60–5.46)	0.29			1.00 (0.33–3.01)	0.99
ART (no vs. yes)	10.65 (1.68–67.69)	0.01	40.26 (4.12–393.62)	0.002	1.09 (0.29–4.21)	0.90	1.25 (0.24–6.58)	0.80
TDF	0.67 (0.08–5.57)	0.71			1.39 (0.39–4.97)	0.61
Protease inhibitor	2.43 (0.85–6.98)	0.10			1.20 (0.52–2.75)	0.67
INSTI	0.39 (0.13–1.11)	0.08			0.75 (0.34–1.66)	0.48
Comorbidities
Hypertension	1.11 (0.43–2.90)	0.83	0.58 (0.15–2.25)	0.43	1.83 (1.02–3.30)	0.04	1.15 (0.58–2.30)	0.69
Dyslipidaemia	1.97 (0.70–5.58)	0.20			1.70 (0.95–3.03)	0.07
Diabetes mellitus	2.82 (0.90–8.85)	0.08	3.30 (0.79–13.88)	0.10	2.21 (1.20–4.09)	0.01	1.68 (0.82–3.44)	0.16
Heart disease	2.21 (0.42–11.66)	0.35	2.71 (0.31–23.70)	0.37	3.23 (1.50–6.95)	0.003	2.45 (1.04–5.77)	0.04
Chronic lung disease	1.63 (0.32–8.21)	0.55			1.44 (0.64–3.20)	0.38
Obesity	1.39 (0.56–3.45)	0.48			1.37 (0.76–2.46)	0.29
BMI	1.02 (0.96–1.07)	0.61			1.00 (0.95–1.05)	0.92
Chronic kidney disease	1.16 (0.24–5.60)	0.85	1.13 (0.14–8.99)	0.91	2.01 (1.02–3.99)	0.045	1.60 (0.71–3.60)	0.26
History of HBV	—	—			0.16 (0.02–1.31)	0.09
History of HCV	0.77 (0.09–6.48)	0.81	2.15 (0.18–26.34)	0.55	2.39 (1.05–5.42)	0.04	3.52 (1.29–9.60)	0.01
HCV viremia	—	—			1.39 (0.43–4.47)	0.58
Malignancy	3.61 (0.99–13.13)	0.052			2.30 (0.73–7.32)	0.16
Solid organ transplant	—	—			1.37 (0.08–22.16)	0.83
Comorbidity burden^a	1.38 (1.03–1.85)	0.03	1.21 (0.88–1.67)	0.25	1.44 (1.20–1.73)	<0.001	1.36 (1.12–1.66)	0.002

aORs adjusted for age, date of SARS-CoV-2 infection, site, illicit drug use, ART, hypertension, diabetes, chronic kidney disease, and history of HCV. aOR, adjusted odds ratio; ART, antiretroviral therapy; AVAMC, Atlanta Veterans Affairs Medical Center; CI, confidence interval; HBV, hepatitis B virus; HCV, hepatitis C virus; INSTI, integrase strand transfer inhibitor; OR, odds ratio; PWH, people with HIV; TDF, tenofovir disoproxil fumarate.
^aaOR adjusted for age only.