HIV & Global Health Rounds
The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease and global public health clinicians,
physicians, and researchers. The goal of these presentations is to
provide the most current research, clinical practices, and trends in HIV,
HBV, HCV, TB, and other infectious diseases of global significance.
The slides from the HIV & Global Health Rounds presentation that you
are about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.
Making sense of the COVID-19
data in Persons with HIV
Edward Cachay MD, MAS
Professor of Clinical Medicine
University of California, San Diego
• Alert but tachypneic
• Diffuse pulmonary rales
• Hepatosplenomegaly
3
T: 101.5 BP 100/60 HR: 110 RR 32x’ O2 Sat 78% on RA wt: 160lb
A 31yo male from El SALVADOR presents with SOB and fatigue
- OFF ART for 2 years
- 1-month productive sputum, night sweats
and intermittent fevers.
- One week prior to admission SOB increased
and came to the ED
Work up
• PCR SARS CoV-2 Positive
• Urine histoplasma Ag Positive
• TB GenXprt Positive w/o resistanse
• CD4: 1
- He was an illegal immigrant from El SALVADOR to GUATEMALA.
- Admitted to the main Guatemalan Medical Center ( ‘Hospital de Roosevelt’)
Amphotericin
Ampi/sulb
Dexametasone
RIPE + B6
Day 3
High flow O2
Fever drops
O2 requirements
decrease
Day 7 Day 10
AKI 2/2 Ampho
Switch to Itraconazole
Day 20
D/c on 3L O2
Referal to
outpatient Pulm
Rehab
Day 30
Ambulatory ART
8 months
later, still
alive & off
O2!
Day 0
Courtesy of Captain Rene Arita MD
ID Fellow from El Salvador Army finishing his ID Fellowship in Guatemala
Relative to PWoH
1. Have PWH been testing at same rates?
2. Do PWH have increased susceptibility to acquiring SARS-CoV-2?
3. Do PWH have a higher risk of hospitalization?
4. If hospitalized due to COVID-19, do PWH have worse clinical outcomes?
5. Do PWH have similar antibody protection after SARS-CoV-2 infection in terms of
magnitude and duration?
Have PWH being tested for SARS-CoV2
in a similar proportion to PWoH?
Overall VA COHORT:
PWH 30,948
PWoH 76,618
Proportion TESTED
PWH 2549 (8.2%)
PWoH 4977 (6.4%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
0
10
20
30
40
50
60
70
80
90
COVID-19
testing
per
1,000
patients
OR: 1.36 (95% CI: 1.29 ̶ 1.43) PWH
PWoH
Week (from 3/1/2020)
VACS Cohort: 1 March ─ 21 June 2020
Park L et al. 23rd International AIDS Conference, abstract LBPEC23, 2020.
CIVET: Corona-Infectious-Virus epidemiology Team
5 clinic cohorts and 1 interval HIV cohort:
Midatlantic permanent group, Kayser northern CA, UNC, Vanderbilt, VACS, MACS/WIHS
P trend < 0.001
Park L et al. 24th CROI, abstract 626, 2021.
0
10
20
30
40
March 1 ̶ August 31, 2020
1 2 3 4 5 6
Proportion
Tested
(%)
Cohort
PWH
PWoH
UC Health Cohort: March 1, 2020 ─ November 30, 2020
PWH
n (%)
PWoH
n (%)
At risk patients 3,609 235,609
Total Tested 1,232 (34%) 22,483 (10%)
P < 0.00001
Tang Michael, Gaufin T, Anson R et al . 24th CROI, abstract 542, 2021.
PWH have been screened more often than
PWoH
• Access to health care
• Difference in test-seeking behavior
• Perceived patient and provider risks of COVID-19
• PWH are in general more likely investigated than PWoH
Do PWH have an increased
susceptibility to SARS-Co-V2?
1 2 3 4 5 7
6 8 9 10 11 12 13 14 15 16
Week (from 3/1/2020)
0
5
10
15
20
25
30
COVID-19
testing
per
100
patients
OR: 1.05 (95% CI: 0.89 ̶ 1.24)
% POSITIVE AMONG THOSE TESTED
PWH 253 of 2549 (9.7%)
PWoH 504 of 4977 (10.1%)
Park L et al. 23rd International AIDS Conference, abstract LBPEC23, 2020.
VACS Cohort: 1 March ─ 21 June 2020
PWoH
PWH
7.4%
7.3% 3.8%
5.0%
6.4%
8.0%
0
10
20
30
40
50
%
Detected
0
10
20
30
40
50
%
Detected
0
10
20
30
40
50
%
Detected
Cohort 1 Cohort 2 Cohort 3
4.2%
7.4%
0
10
20
30
40
50
%
Detected
Cohort 4
3.8%
5.6%
0
10
20
30
40
50
Cohort 5
0
10
20
30
40
50
3.9%
0.0%
Cohort 6
%
Detected
%
Detected
Positive COVID-19 test among the CIVET: Corona-Infectious-Virus epidemiology Team
PWH PWoH
Park L et al. 24th CROI, 2021 abstract 626, 2021.
PWH, N (%) PWoH, N (%)
At risk patients 108,062 19 345 499
Total diagnosed 2409 (2.2%) 375 260 (1.9%)
Rate per 1000 27.5 19.4
RR: 1.43 [95%CI, 1.38-1.48]
*sRR: 0.94 [95%CI, 0.91-0.97)
* controlling for age, sex, and region
Tesoriero J, et al. JAMA Netw Open. 2021;4(2):e2037069.
Data from Statewide in New York: march 1 to June 7, 2020
UC Health Cohort: March 1, 2020 ─ November 30, 2020
PWH, N (%) PWoH, N (%)
At risk patients 3,609 235,609
Total Tested 1,232 (34%) 22,483 (10%)
Diagnosed 104 (8%) 603 (3%)
Population frequency % (95 CI) 2.88 % (2.38 to 3.48 ) 0.26% (0.24 to 0.28)
Tang Michael, Gaufin T, Anson R et al . 24th CROI, abstract 542, 2021.
Overall the proportion of patients who tested positive for COVID-19 was higher among PWH than those without HIV
aOR: 3.41 (2.65─4.39)
*Adjusted Odds Ratio for age, gender, race/ethnicity, diabetes, and obesity and other
covariates via backwards model selection
0
10
20
30
40
50
PWH w/COVID-19 PWH w/o COVID-19 PWoH w/ COVID-19
Braunstein SL, et al. Clin Infect Dis. 2020 Nov 30 Epub ahead of print.
New York City: A Population-Level Analysis of Linked Surveillance Data
Black White Very high poverty (≥30% below FPL)*
Hispanic
%
* Less than 28,236$ annually for a 3-member household
N =113 907 N= 202 012
N =2410
31.6%
16.1%
25.1%
aRR, 1.59 [95%CI, 1.40-
1.81])
aRR, 2.08 [95%CI, 1.83-
2.37
March 1 to June 2, 2020
86.4% 78.6%
33%
Data from Spain: universal health care system
30.4 (26.7 ─ 34.6)
COVID-19 diagnosis rates
Per 10,000
41.7
30.0 (29.8 ─ 30.2)
S Rate: 33. 0 Excluding HCWs
PWH PWoH (General population)
Antibody/ Total (%) Crude OR (95% CI) P a OR (95% CI) P
Country of birth
Spain 7.2% Ref Ref
Latin America 14.3% 2.16 (1.36─3.42) .001 2.34 (1.42─3.85) .001
Other 4.4% 0.60 (0.21─1.68) .328 0.64 (0.22─1.88) .419
“Data from 1076 PWH regardless of symptoms”
Berenguer J, 24TH CROI , Abstract 549, 2021
Del Amo J et al. Ann Intern Med. 2020;173:536-541
Social and health disparities have a color… skin but
also passport!
Madrid a city of
contrasts!
Does the level of HIV control affect COVID-19
acquisition among PWH?
Baseline characteristic
Total
COVID-19 Case
Yesa Nob RR c 95% CI p-value
N (% of total) 15,969 582 (3.6%) 15,387 (96.4%)
Nadir CD4+ count (cells/mm3)
RR (≤350 vs. >350 cells/mm3)
<200 43.1% 44.4% 43.1%
1.17 0.99 ̶ 1.39 0.071
200-349 23.8% 26.7% 23.7%
350-499 15.4% 13.5% 15.5%
ref
500
17.7% 15.4% 17.7%
CD4+ count (cells/mm3) RR (≤350 vs. >350 cells/mm3)
<200 6.5% 6.6% 6.5%
1.04 0.84 ̶ 1.28 0.714
200-349 10.9% 10.7% 110.9%
350-499 15.8% 15.1% 15.8%
ref
500
66.9% 67.6% 66.9%
ART status 95.2% 95.4% 95.2% 1.02 0.70 ̶ 1.49 0.929
Undetectable viral load (<50
copies/mL)
(85.4%) (85.7%) (85.4%) 1.10 0.8 ̶ 1.39 0.424
Data from the CNICS Cohort
Shapiro A et al., 24th CROI 2021 abstract 543, 2021
Risk of diagnosis using population data from Statewide in
New York: March 1 – June 7, 2020
Population
size
№ Diagnosed Rate per
1000 PWH
Rate ratio (95% CI)
Unadjusted Adjusted
CD4 ≥ 500 63712 1774 27.84 1 [ Reference ] 1 [ Reference ]
CD4: 200-499 27905 843 30.21 1.08 (0.99─1.18) 1.02 (0.94─1.11)
CD4 < 200 7498 270 36.01 1.29 (1.14─1.47) 1.22 (1.07─1.38)
Other 8947 101 11.29 NA NA
Viral Suppression*
Yes 87 480 2628 30.04 1 [ Reference ] NA
No 12 027 267 22.20 0.74 (0.65─0.84) NA
Other 8555 93 10.87 NA NA
Tesoriero J, et al. JAMA Netw Open. 2021;4(2):e2037069.
* HIV VL < 200 copies/mL
Model adjusted for age, sex, race/ethnicity, HIV
transmission risk , region of residence.
PWH and risk of being diagnosed with COVID-19
• The evidence suggest that PWH have a heterogeneous risk
of acquiring SARS-CoV-2
• Those burden by social and structural health disparities
and/or have the lowest CD4 Cell count appears to be at the
highest risk of infection with SARS-CoV-2.
Do PWH have worse clinical outcomes
after COVID-19 diagnosis?
Subsequent population-based cohort studies
have shown a signal worse outcomes
Diagnosis
Hospitalization
ICU/
Mechanical
ventilation
Mortality
Summary of 1st wave of studies: No worse outcomes
Time Region Design Setting Number Hospitalized ICU Died VL <
200
CD4<
200
Comment Reference
3/30 ─ 5/20 /20 Rhode Island,
US
Case series Inpt/outp 27 9/27 (33%) 0 1* ALL 1 19 of 27 non-white JIAC 2020,
23:e25573
2/2─ 4/16/20 Milan, Italy Case series Inpt/outp 47 13/47 (28%) 2 2** 44 of 47 0 Good outcome CID 2020;71:2276–
8
3/11─4/17/20 Munich,
Germany
Cases series Inpt/outp 33 14/33 (42%) 6 3 30 of 32 1 Infection (2020)
48:681–686
3/15─4/15/20 New York, USA Case series Inpatient 31 4 8 (25.8%) ALL 7 ¾ non-whites CID 2020 1:2294–7
2/1─ 4/30/20 Madrid, Spain Cohort Inpt/oupt 51
1.8% (95% CI 1.3–2.3)
28 6 (12%) 2 (4%) ALL 6 follow-up qualitative
RT-PCR assays
Lancet HIV.
2020;7:e554-564.
3/10─5/11/20 New York, USA Cohort Inpatient 4613
(100 HIV+)
ALL HR 1.73
[95% CI:
1.12 to 2.67]
HIV+:22%
HIV-: 24%)
81 of 90 2/3 non-white
No deaths among
PWH w/ VL > 200
JAIDS. 2021
1;86:224-230
3/4─4/3/20 New York, USA Matched
control (1:2)
Inpatient HIV+ 21
HIV- 42
ALL 6 (28.6%)
7 (16.7%)
6 (28.6%)
10 (23.8%)
20 0f 21 1 HIV+ had more non-
white
JAIDS, 2020;85:6-
10.
3/10─5/15/20 New York, USA Matched
control (1:2)
Inpatient HIV+ 30
HIV- 90
ALL HIV+ 4 (13%)
HIV-21 (23%)
HIV+ 2(7%)
HIV-14(16%)
ALL 7 ¾ non-white OFID. 2020
1;7(8):ofaa327
3/12─4/23/2 New York, USA Matched
control (1:5)
Inpatient 88 HIV+
405 HIV-
ALL HIV+ 18%
HIV- 23%
HIV+ 21%
HIV - 20%
66 7 ¾ non white CID 2020;71:2933-
2293
3/1─6/21/20 USA (VACS) Matched
control (1:2)
Inpt/outp POSITIVE
HIV+ 253
HIV- 504
HIV+ 86(35%)
HIV- 178 (35%)
HIV+ 35(14%)
HIV- 75 (25%)
HIV+ 24(10%)
HIV- 56 (11%)
More testing but no
increased positivity
Park L et al.
IAC2020
Cachay et al. In Progress
Among major shortcomings 1st wave of initial studies:
• Denominator comparison is not accurate: Focus only on those
diagnosed and with access to care.
• Missed or inaccurate case ascertainment of patients admitted to
different health care systems or dying outside care services
So let’s review the contribution of the 2nd wave of
studies…
The NC3 Cohort: characteristics of study participants
1 Jan 2020 ̶ 6 Feb 2021
- 39 centers
across USA.
- ≥ 18 years
- RT-PCR
positive.
Overall
N=509,092
PWoH/No SOT
N=501,416
PWoH only
N=2,932
SOT only
N=4,633
PWH & SOT
N=111
Age, median (IQR) 46 (31-60) 45 (30-60) 48 (35-59) 57 (46-66) 55 (44-64)
Age≥60, N (%) 135,332 (26.6) 132,579 (26.4) 700 (23.9) 2,014 (43.5) 39 (35.1)
Male sex, N(%) 230,690 (45%) 225931 (45.1) 1,942 (66.2) 2,745 (59.2) 72 (64.9)
Race/ethnicity, N (%)
Black Hispanic 825 (0.2) 800 (0.2) ≤20 ≤20 ≤20
Black non-Hispanic 83,910 (16.5) 81,310 (16.2) 1,289 (44%) 1259 (27.2) 52 (46.8)
White Hispanic 27,146 (5.3) 26,711 (5.3) 147 (5) 283 (27.2) ≤20
White non-Hispanic 279,923 (55) 276,782 (55.2) 915 (31.2) 2,192 (47.3) 34 (30.6)
Others 117,288(23) 115,813 (23.1) 566 (19.3) 889 (19.2) ≤20 (18)
Jing S et al. . 24th CROI, oral abstract 103, 2021
N3C Cohort: Risk of hospitalization according to HIV and SOT status
0
0.25
0.50
0.75
1.00
0 10 20 30 40
Nº at risk
447960
61
1904
2591
PWoH/SOT-
PWH/SOT+
PWH alone
SOT alone
411794
40
1631
1936 1829 1780 1747
1592 1557 1533
37 37 35
406789 403121 400608
Days since positive covid test
Probability
of
not
being
hospitalized
(%)
9.8%
16.8%
30.1%
39.3%
11.3%
20.1%
33.4%
45.9%
PWoH/SOT-
PWH/SOT+
PWH alone
SOT alone
Jing S et al. . 24th CROI, oral abstract 103, 2021
Hospitalization risk in the NC3 Cohort comparing PWH with SOT
and general population
Model a: adjust for age, sex, race/ethnicity, and study site
Model b: adjust for age, sex, race/ethnicity, and study site, severe liver disease, DM2, Cancer, renal disease and Nº of
comorbidities (0,1,2,≥ 3)
Immunosuppression
groups
Crude estimates Adjusted estimatesa Adjusted estimatesb
OR (95% CI) P-value OR (95% CI) P-value OR (95% CI) P-value
PWoH & No SOT
(n = 501,416)
Reference ─ Reference ─ Reference ─
PWH only
(n= 2,932)
2.14 (1.99─2.30) < 0.01 1.63 (1.5─1.76) < 0.01 1.32 (1.22─1.43) < 0.01
SOT only
(n = 4,633)
4.0 (3.77─4.25) < 0.01 3.07 (2.88─3.27) < 0.01 1.69 (1.58─1.81) < 0.01
PWH & SOT
(n= 111)
5.37 (3.57─8.06) < 0.01 3.50 (2.27─5.42) < 0.01 1.65(1.06─2.56) 0.03
Jing S et al. . 24th CROI, oral abstract 103, 2021
A large national USA Cohort: The TriNetX health
research network
Yendewa GA et al . 24th CROI, abstract LB 548, 2021
Characteristics PWH
( n =1,638)
PWoH
(N = 295,556)
P
Age (mean ± SD) 43.3 ± 13.6 46.5 ± 18.7 <0.001
Male 1137 (69%) 130866 (44%) <0.001
AA or Hispanic 1102 (67%) 100133 (34%) <0.001
CV disease 767 (47%) 77178 (26%) <0.001
Obesity 404 (25%) 43883 (15%) <0.001
- 297, 194 COVID-19 cases
> 44 healthcare organizations in US
- 1638 PWH (0.6%)
> 83% on ART
> 48% had HIV VL < 20 copes/mL
PWH vs PWoH
OR of Hospitalization:
1.26 , 95% CI: 1.04─1.53, p =0.023
Do HIV viral suppression and CD4 cell count
level impact the risk of hospitalization after
COVID-19-diagnosis?
Population
size
№ Rate per
1000 diagnoses
Rate ratio (95% CI)
Unadjusted Adjusted
HIV suppressed 87480 756 287.7 1 [Reference] NA
HIV unsuppressed 12027 105 393.3 1.37 (1.11─1.68) NA
Other 8555 35 376.3 NA NA
CD4≥500 63712 437 246.3 1 [ Reference ] 1 [ Reference ]
CD4: 200-499 27905 298 353.5 1.44 (1.24─1.66) 1.29 (1.11─1.49)
CD4<200 7498 126 466.7 1.89 (1.55─2.31) 1.69 (1.38─2.07)
Risk of hospitalization using population data from
Statewide in New York: March 1 – June 7, 2020
Tesoriero J, et al. JAMA Netw Open. 2021;4(2):e2037069.
Model adjusted for age, sex, race/ethnicity, HIV transmission risk , region of residence
Predictors of Hospitalization among PWH:
IDSA registry of USA and international centers N =286
Characteristics OR ( 95% CI) P-value
Age, years 1.08 (1.04─1.07) 0.03
CD4 > 500 Reference ─
CD4 200-500 1.12 (1.1─12.22) 0.03
CD4 < 200 3.67 (1.64─17.1) < .01
CKD 4.08 (1.45─11.52) < .01
COPD 4.06 (1.87─8.81) < .01
HIV with No comorbidity Reference ─
1-2 comorbidities 1.13 (0.49─2.6) 0.78
≥ 3 comorbidities 3.57 (1.29─9.9 .01
Dandachi et al, Clinical Infectious disease Nov 2020 Epub Ahead of Print
Generalized Estimating Equation (GEE) adjusted models*
Model A: The model is adjusted for age, sex, race/ethnicity, years with HIV, CD4 count, HIV viral load suppression, ART regimen, HTN,
DM2, COPD, CKD, CV disease, active malignancy, and chronic liver disease
Model A
Model B
Model B: The model for the associations between hospitalization, and the comorbidity burden is adjusted for age, sex, and race/ethnicity.
Predictors of hospitalization for PWH and COVID-19- CNICS
Characteristics Not hospitalization
N = 160 (81%)
Hospitalization
N = 38 (19%)
RR ( 95% CI) P-value
Age ≥ 60 34 (21%) 14 (375) 2.0 (1.13─3.54) 0.017
Female 41 (26%) 13 (34%) 1.02 (0.55─1.88) 0.962
Black vs non-black 77 (48%) 27 (71%) 1.42 (0.69─2.91) 0.336
CD4 ≤ 350 30 (20%) 12 (32%) 1.77 (1.05─2.98) 0.032
On ART 156 (98%) 36 (95%) ─ ─
Undetectable ART 126 (80%) 32 (84%) ─ ─
HCV 20 (13%) 6 (16%) 1.05 (0.48─2.33) 0.900
DM2 33 (21%) 115 (40%) 1.49 (0.85─2.61) 0.166
eGFR < 60 17 (11%) 11 (30%) 1.76 (0.99─3.13) 0.051
BMI ≥ 30 60 (40%) 24 (69%) 1.96 (1.02─3.78) 0.044
COPD 9 (6%) 3 (8%) ─ ─
Shapiro A et al. 24th CROI 2021 abstract 543, 2021
Adjusted rate ratio (95% CI)
0.5 0.6 0.7 0.8 0.9 1 1.5 2 2.5 3.0 3.5 4
Sex female: 95% CI: 0.87─1.16
Age ≥ 60: 95% CI: 2.66─5.41
Factors associated with hospitalization among PWH─ Data from NYS
Adjusted analysis for risk of hospitalization among PWH NYS march 1 to June 7, 2020
Tesoriero J, et al. JAMA Netw Open. 2021;4(2):e2037069.
Hospitalization rates per 1000
persons
6229.87 vs 163.86
RR, 1.83 [95% CI, 1.72─1.96)
PWH PWoH
Models adjusted for age, region of residency, HIV risk factor, CD4
Viral load not included as considered mediator of CD4 and COIVD-19 outcomes
4.5 5
1.01
Black : 95% CI: 0.89─1.48
1.15
3.09
1.11
Hispanic : 95% CI: 0.87─1.43
1.13 MSM + IDU: 95% CI: 0.83─1.53
1.13 IDU: 95% CI: 0.93─1.37
1.29 CD4: 200-499: 95% CI: 1.11─1.49
CD4: <200: 95% CI: 1.38─2.07
1.69
Ref: male
Ref: white
Ref: MSM
Ref: ≥500
1.86 Age 40-59: 95% CI: 1.40─2.46
Ref: < 40
Comorbidity count of PWH diagnosed with COVID-19 according to
hospitalization status
13%
40%
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5
Hospitalized Not hospitalized
Barbera L et al. . 24th CROI, abstract 546, 2021
Comorbidity count and odds of COVID-19 hospitalization among PWH
0.2 2 20
5+
4
3
2
1
0.81
1.42
3.19
4.73
6.08
(0.29 ̶ 2.24)
(0.49 ̶ 4.09)
(1.04 ̶ 9.80)
(1.59 ̶ 14.10)
(1.93 ̶ 19.15)
Comorbidity
count
Odds Ratio (95% CI)
Barbera L et al. . 24th CROI, abstract 546, 2021
N = 180, 97% on ART of whom 91% were suppressed
Overall, the data suggest so far that:
• PWH have an increased risk (1.3 to 1.5 fold) higher risk of hospitalization
than PWoH
• The risk is strongly mediated by the number and status of medical
comorbidities
• Low CD4 cell counts seem to have an independent effect in increasing
the risk of hospitalization due to COVID-19 regardless of comorbidity
burden
• When studies control for comorbidity burden, age and BMI, neither
race/ethnicity, HIV risk factor, ART class affect the risk of hospitalization
due to COVID-19
Populations based cohort studies have shown a
signal of worse mortality in HIV patients who
acquired COVID-19 in developed and developing
countries
UK: Cumulative mortality: Feb 1 to June 22, 2020
17 282 905 adults were included, of whom 27 480 (0.16%) had HIV recorded.
14 882 COVID-19 deaths occurred during the study period, with 25 among people with HIV
HR: 2.90 (95% CI 1.96–
4.30)
The association was attenuated, but risk remained high, after
adjustment deprivation*, ethnicity, smoking and obesity.
Bhaskaran K et al. The Lancet. 2020;8(1):E24-E32. A
0
Feb 1 March 1April 1 May 1 June 1 July 1
Date (2020)
.05
.10
.15
100
Cumulative
mortality
(%)
*derived from the patient’s postcode at lower super
output area level in the UK
adjusted for age, sex only
HR: 2.59 (95% CI 1.74–
3.84)
HR: 2.30 (95% CI 1.55–3.41)
Adjustment for potentially mediating comorbidities reduced
the HR slightly
Western Cape, South Africa: 1 March-9 June 2020
Comparison of adjusted HRs and 95% CIs for associations with COVID-19 death from Cox proportional hazards model
0.7 2 5 40
1
1 2 5 40
0.7
female
male
20─39
40─49
50─59
60─69
≥ 70
No comorbidities
A1c < 7%
A1c 7─8.9%
A1c ≥9%
No A1c
HTN
CKD
COPD/Asthma
Previous TB
Current TB
HIV positive
female
male
20─39
40─49
50─59
60─69
≥ 70
No comorbidities
A1c < 7%
A1c 7─8.9%
A1c ≥9%
No A1c
HTN
CKD
COPD/Asthma
Previous TB
Current TB
HIV positive
Age
DM2
Age
DM2
A. all public-sector patients ≥20 years old with a public-sector health
visit in the previous 3 years (n = 3 460 932)
B. all adult COVID-19 cases diagnosed before 1 June 2020 (n = 15 203)
Boulle A et al, Clinical Infectious disease August 29, 2020 Epub Ahead of Print
Data from South Africa:
Comparison of adjusted HRs and 95% CIs for associations with COVID-19 death from Cox proportional hazards model
0.7 2 5 40
1
1 2 5 40
0.7
female
male
20─39
40─49
50─59
60─69
≥ 70
No comorbidities
A1c < 7%
A1c 7─8.9%
A1c ≥9%
No A1c
HTN
CKD
COPD/Asthma
Previous TB
Current TB
HIV positive
female
male
20─39
40─49
50─59
60─69
≥ 70
No comorbidities
A1c < 7%
A1c 7─8.9%
A1c ≥9%
No A1c
HTN
CKD
COPD/Asthma
Previous TB
Current TB
HIV positive
Age
DM2
Age
DM2
B. all hospitalized COVID-19 cases (n = 2978)
A. all adult COVID-19 cases diagnosed before 1 June 2020 (n = 15 203)
After adjustment for age, BMI and comorbidities, the independent significant effect on
population mortality persisted ~ 1.4 fold
Boulle A et al, Clinical Infectious disease August 29, 2020 Epub Ahead of Print
If hospitalized due to COVID-19, do
PWH have worse clinical outcomes?
Data from cohort studies on worse clinical
outcomes and mortality: N3C NIH cohort
Immunosupression
groups
Crude estimates Adjusted estimates*
OR (95% CI) P-value OR (95% CI) P-value
PWoH & No SOT Reference ─ Reference ─
PWH only 1.93 (1.63─2.28) < 0.01 1.73 (1.45─2.06) < 0.01
SOT only 2.66 (2.40─2.96) < 0.01 2.02 (1.81─2.25) < 0.01
PWH & SOT 4.35 (2.54─7.45) < 0.01 3.92 (2.21─6.96) < 0.01
* Model is adjusted for age, sex, race/ethnicity, study site
Odds of mechanical ventilation after hospitalization
Jing S et al. . 24th CROI, oral abstract 103, 2021
Predictors of Severe outcome* among PWH:
IDSA registry of USA and international centers N =286
Characteristics OR ( 95% CI) P-value
Age, years 1.04 (1.0─1.07) 0.02
CD4 > 500 Reference ─
CD4 200-500 1.93 (0.73─5.06) 0.18
CD4 < 200 2.8 (1.02─7.67) 0.05
HTN 2.43 (1.2─4.93) 0 .01
COPD 3.37 (1.63─6.97) < .01
HIV with No comorbidity Reference ─
1-2 comorbidities 2.21 (0.42─11.7) 0.35
≥ 3 comorbidities 5.40 (1.02─28.54 0.05
Dandachi et al, Clinical Infectious disease Nov 2020 Epub Ahead of Print
Generalized Estimating Equation (GEE) adjusted models*
Model A: The model is adjusted for age, sex,
race/ethnicity, years with HIV, CD4 count, HIV viral
load suppression, ART regimen, HTN, DM2, COPD,
CKD, CV disease, active malignancy, and chronic
liver disease
Model A
Model B Model B: The model for the associations
between hospitalization, and the comorbidity
burden is adjusted for age, sex, and
race/ethnicity.
* Severe outcome is defined as a composite outcome of intensive care admission,
invasive mechanical ventilation, or death
IDSA* registry: overall ICU and survival curves by CD4 status
Overall
survival
(%)
0.0
0.2
0.4
0.6
0.8
1.0
0 5 10 15 20 25 30 35 0 5 10 15 20 25 30 35
ICU-free
survival
(%)
0.0
0.2
0.4
0.6
0.8
1.0
+ censored
Logrank p =0.036
+ censored
Logrank p =0.05
Time in days Time in days
1 38 37 36 33 33 32 32 32
2 94 92 91 89 89 85 83 81
3 116 116 114 113 112 111 111 110
1 38 29 28 27 27 27 27 27
2 94 87 82 80 79 79 78 78
3 116 108 105 104 103 102 102 102
CD4: < 200 200 ─500 <500
* Includes one site from Spain Dandachi et al, Clinical Infectious disease Nov 2020 Epub Ahead of Print
CoVIH-19 Study across 39 centers in Spain
“HIV Infection was associated with higher incidence of death”
( N = 204 ), Feb 26 ̶ Sept 21, 2020
Competing-risks regression analysis
Cumulative
incidence
0.02
0.04
0.06
0.08
0
0 10 20 30
Days after admission
subHR 3.45, 95% CI 1.47 ─8.11, p =0.0045
PWH
PWoH
The risk of death remain but less strong decreased after adjustment for
liver disease, CV and obesity aOR: 5.27 CI 1.00 ─ 27.72, p =0.049
ART: NNRTI 17%, PI: 23%, INSTI: 70%,
89% NRTI (6% TDF, 45% TAF, and 31% ABC)
Mortality among PWH was not associated with:
Current or Nadir: CD4, CD4/CD8 ratio
Detectable HIV RNA
Specific ART agent (TDF/TAF))
Blanco JL et al . 24th CROI, abstract 641, 2021.
Trends at UC San Diego Health
Outcomes
PWH,
N (%)
Non-PWH,
N (%)
Positive aOR*
(95% CI)
At risk patients 3,609a 235,609a
Hospitalization 16 (15%) 76 (13%)
ICU 6 (6%) 26 (4%) 1.33 (0.44, 3.96)
Intubation 6 (6%) 10 (2%) 2.35 (0.62, 8.96)
Death 2 (2%) 11 (2%) 3.04 (0.46, 19.94)
*Adjusted Odds Ratio for age, gender, race/ethnicity, diabetes, and obesity and other covariates via
backwards model selection
a. Percentage of all patients with established primary care at UCSD
Tang Michael, Gaufin T, Anson R et al . 24th CROI, abstract 542, 2021.
Are there special considerations for SARS-
CoV-2 immune responses in PWH?
Data from UCSF: Match 1-2 outpatients PWoH based on age (+/- 5 years) and
date of collection
IgG levels by HIV status among those
with reactive SARS-CoV-2 IgG
Relative
Fluorescent
Units
(Mean
±
1
SE;
log10
scale)
PWoH
N = 70
PWH
N = 31
Neutralizing Ab titers: 63% (95% CI: 2%─78% lower)
lower among PWH vs. PWoH with past infection
Avidity: No difference (+7.9%; 95% CI: -4%─ +20%)
Unknowns:
- Proportion of asymptomatic and hospitalized
between groups comparable
- Median CD4 of PWH
1000
300
100
45% lower
95% CI: 22%─61%
Spinelli M al. 24th CROI, abstract 627, 2021
Data from Miami CFAR: “All symptomatic outpatients”
PWH
N = 17
PWoH
N = 19
PWH
N = 17
PWoH
N = 19
“All PWH had viral load < 500 copies./mL and a median CD4: 859”
IgM PWH vs PWoH IgM PWH vs PWoH
T1 = W2
T2 = W4
T3 = W12
*Ab units based on the positive control standard
IgM
(relative
titer*)
IgG
(relative
titer*) Alcaide M et al. 24th CROI, abstract 260, 2021
20000
40000
60000
500000
1000000
1500000
2000000
Cut-off
54234
0
T0 T1 T2 T3 T3
T2
T1
T0
Cut-off
12646
T0 T1 T2 T3 T0 T1 T2 T3
0
5000
10000
15000
20000
1000000
2000000
3000000
4000000
5000000
Data from Oxford: Serology and T cell response assessment
Median range
CD4 560 (133─1360
CD4:CD8 0.87 (0.17─2.54)
All PWH had viral load < 50
copies/mL
76.6% (n=36) Mild
19.2% (n=9) moderate (hospital)
4.3% (n= 2) asymptomatic
74.2% (n=26) Mild
11.4% (n=4) moderate (hospital)
14.3% (n= 5) asymptomatic
PWH
PWH
N = 47
PWoH
N = 35
PWoH
Convalescent phase
148 (46-273)
146 (101-220)
PWH
PWoH
Days post-symptom onset
80
60
40
20
Age
(years)
0
0 100 200 300
Alrubayyi At et al. 24th CROI, abstract 262, 2021
Comparable Ab levels with neutralizing
activity among PWH and PWoH
S1
IgG
Titer
mg/mL
N
IgG
Titer
mg/mL
ID
50
neutralization
titer
Asymptomatic
Non hospitalized
Hospitalized
PWoH PWH
0.1
1
10
100
PWoH PWH
100
10
1
0.1
PWoH PWH
10
100
1000
10000
Detection Limit
Minimum ID50
Potent
Alrubayyi At et al. 24th CROI, abstract 262, 2021
SARS-Cov-2 INF-g T-cell Elispot responses
did not differ by HIV status
∆
5FU/
10
6
PBMCs
%
of
specific
T
cells
CD4 T cell cytokines preferentially reacted
with spike or membrane/nucleocapside
proteins regardless of HIV status
ns ns ns
PWoH
PWH
100
10
1000
1
*** *
PWoH PWH
0.0
0.5
1.5
1.0
CD4 CD4 CD4 CD4
CD8 CD8 CD8 CD8
Spike Spike
M/N M/N
***
**
Alrubayyi At et al. 24th CROI, abstract 262, 2021
SARS-Cov-2 specific T-cell responses correlate with
the CD4:CD8 ratio and % naïve CD4T Cells in PWH
CD4:CD8
ratio
Total
SARS-CoV-2
T
Cells
∆
5FU/
10
6
PBMCs
r =0.3820
p=0.037
r =0.5518
p=0.0143
0
1
2
3
0 200 400 600
Total SARS-COV-2 T cells ∆ 5FU/ 106 PBMCs
100
200
300
400
0
0 20 40 60 80
% of naïve CD4 T cells CCR7+ CD45RA+
Alrubayyi At et al. 24th CROI, abstract 262, 2021
Conclusions
- The risk of COVID-19 acquisition is likely influence by structural social and health disparities,
prevalent among PWH rather than a strong biological effect.
- PWH with high burden of comorbidities and/or have low CD4 cell count seem to have an
increase risk of hospitalization.
- PWH tend to have worse clinical outcomes reflected by increased frequency of ICU admission
and mechanical ventilation than PWoH
- PWH have ~ 1.3 to 1.5 increased mortality due to COVID-19 not fully explained by BMI, age,
and comorbidity burden. Unaccounted confounders? Oversimplification/correction?
- Most PWH mount a good antibody response to SARS-CoV-2 similar than PWoH, however, PWH
with low CD4:CD8 ration could have compromise immune response to SARS-CoV-2
“ Education is the most powerful tool to change
the world, and it should not be a privilege of
some but a right for all”
̶ Edward Cachay
# zerosexism #zerohate # zerodiscrimination

04.09.21 | Making Sense of the COVID-19 Data in Persons with HIV

  • 1.
    HIV & GlobalHealth Rounds The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease and global public health clinicians, physicians, and researchers. The goal of these presentations is to provide the most current research, clinical practices, and trends in HIV, HBV, HCV, TB, and other infectious diseases of global significance. The slides from the HIV & Global Health Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission.
  • 2.
    Making sense ofthe COVID-19 data in Persons with HIV Edward Cachay MD, MAS Professor of Clinical Medicine University of California, San Diego
  • 3.
    • Alert buttachypneic • Diffuse pulmonary rales • Hepatosplenomegaly 3 T: 101.5 BP 100/60 HR: 110 RR 32x’ O2 Sat 78% on RA wt: 160lb A 31yo male from El SALVADOR presents with SOB and fatigue - OFF ART for 2 years - 1-month productive sputum, night sweats and intermittent fevers. - One week prior to admission SOB increased and came to the ED
  • 4.
    Work up • PCRSARS CoV-2 Positive • Urine histoplasma Ag Positive • TB GenXprt Positive w/o resistanse • CD4: 1 - He was an illegal immigrant from El SALVADOR to GUATEMALA. - Admitted to the main Guatemalan Medical Center ( ‘Hospital de Roosevelt’)
  • 5.
    Amphotericin Ampi/sulb Dexametasone RIPE + B6 Day3 High flow O2 Fever drops O2 requirements decrease Day 7 Day 10 AKI 2/2 Ampho Switch to Itraconazole Day 20 D/c on 3L O2 Referal to outpatient Pulm Rehab Day 30 Ambulatory ART 8 months later, still alive & off O2! Day 0
  • 6.
    Courtesy of CaptainRene Arita MD ID Fellow from El Salvador Army finishing his ID Fellowship in Guatemala
  • 7.
    Relative to PWoH 1.Have PWH been testing at same rates? 2. Do PWH have increased susceptibility to acquiring SARS-CoV-2? 3. Do PWH have a higher risk of hospitalization? 4. If hospitalized due to COVID-19, do PWH have worse clinical outcomes? 5. Do PWH have similar antibody protection after SARS-CoV-2 infection in terms of magnitude and duration?
  • 8.
    Have PWH beingtested for SARS-CoV2 in a similar proportion to PWoH?
  • 9.
    Overall VA COHORT: PWH30,948 PWoH 76,618 Proportion TESTED PWH 2549 (8.2%) PWoH 4977 (6.4%) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 0 10 20 30 40 50 60 70 80 90 COVID-19 testing per 1,000 patients OR: 1.36 (95% CI: 1.29 ̶ 1.43) PWH PWoH Week (from 3/1/2020) VACS Cohort: 1 March ─ 21 June 2020 Park L et al. 23rd International AIDS Conference, abstract LBPEC23, 2020.
  • 10.
    CIVET: Corona-Infectious-Virus epidemiologyTeam 5 clinic cohorts and 1 interval HIV cohort: Midatlantic permanent group, Kayser northern CA, UNC, Vanderbilt, VACS, MACS/WIHS P trend < 0.001 Park L et al. 24th CROI, abstract 626, 2021. 0 10 20 30 40 March 1 ̶ August 31, 2020 1 2 3 4 5 6 Proportion Tested (%) Cohort PWH PWoH
  • 11.
    UC Health Cohort:March 1, 2020 ─ November 30, 2020 PWH n (%) PWoH n (%) At risk patients 3,609 235,609 Total Tested 1,232 (34%) 22,483 (10%) P < 0.00001 Tang Michael, Gaufin T, Anson R et al . 24th CROI, abstract 542, 2021.
  • 12.
    PWH have beenscreened more often than PWoH • Access to health care • Difference in test-seeking behavior • Perceived patient and provider risks of COVID-19 • PWH are in general more likely investigated than PWoH
  • 13.
    Do PWH havean increased susceptibility to SARS-Co-V2?
  • 14.
    1 2 34 5 7 6 8 9 10 11 12 13 14 15 16 Week (from 3/1/2020) 0 5 10 15 20 25 30 COVID-19 testing per 100 patients OR: 1.05 (95% CI: 0.89 ̶ 1.24) % POSITIVE AMONG THOSE TESTED PWH 253 of 2549 (9.7%) PWoH 504 of 4977 (10.1%) Park L et al. 23rd International AIDS Conference, abstract LBPEC23, 2020. VACS Cohort: 1 March ─ 21 June 2020 PWoH PWH
  • 15.
    7.4% 7.3% 3.8% 5.0% 6.4% 8.0% 0 10 20 30 40 50 % Detected 0 10 20 30 40 50 % Detected 0 10 20 30 40 50 % Detected Cohort 1Cohort 2 Cohort 3 4.2% 7.4% 0 10 20 30 40 50 % Detected Cohort 4 3.8% 5.6% 0 10 20 30 40 50 Cohort 5 0 10 20 30 40 50 3.9% 0.0% Cohort 6 % Detected % Detected Positive COVID-19 test among the CIVET: Corona-Infectious-Virus epidemiology Team PWH PWoH Park L et al. 24th CROI, 2021 abstract 626, 2021.
  • 16.
    PWH, N (%)PWoH, N (%) At risk patients 108,062 19 345 499 Total diagnosed 2409 (2.2%) 375 260 (1.9%) Rate per 1000 27.5 19.4 RR: 1.43 [95%CI, 1.38-1.48] *sRR: 0.94 [95%CI, 0.91-0.97) * controlling for age, sex, and region Tesoriero J, et al. JAMA Netw Open. 2021;4(2):e2037069. Data from Statewide in New York: march 1 to June 7, 2020
  • 17.
    UC Health Cohort:March 1, 2020 ─ November 30, 2020 PWH, N (%) PWoH, N (%) At risk patients 3,609 235,609 Total Tested 1,232 (34%) 22,483 (10%) Diagnosed 104 (8%) 603 (3%) Population frequency % (95 CI) 2.88 % (2.38 to 3.48 ) 0.26% (0.24 to 0.28) Tang Michael, Gaufin T, Anson R et al . 24th CROI, abstract 542, 2021. Overall the proportion of patients who tested positive for COVID-19 was higher among PWH than those without HIV aOR: 3.41 (2.65─4.39) *Adjusted Odds Ratio for age, gender, race/ethnicity, diabetes, and obesity and other covariates via backwards model selection
  • 18.
    0 10 20 30 40 50 PWH w/COVID-19 PWHw/o COVID-19 PWoH w/ COVID-19 Braunstein SL, et al. Clin Infect Dis. 2020 Nov 30 Epub ahead of print. New York City: A Population-Level Analysis of Linked Surveillance Data Black White Very high poverty (≥30% below FPL)* Hispanic % * Less than 28,236$ annually for a 3-member household N =113 907 N= 202 012 N =2410 31.6% 16.1% 25.1% aRR, 1.59 [95%CI, 1.40- 1.81]) aRR, 2.08 [95%CI, 1.83- 2.37 March 1 to June 2, 2020 86.4% 78.6% 33%
  • 19.
    Data from Spain:universal health care system 30.4 (26.7 ─ 34.6) COVID-19 diagnosis rates Per 10,000 41.7 30.0 (29.8 ─ 30.2) S Rate: 33. 0 Excluding HCWs PWH PWoH (General population) Antibody/ Total (%) Crude OR (95% CI) P a OR (95% CI) P Country of birth Spain 7.2% Ref Ref Latin America 14.3% 2.16 (1.36─3.42) .001 2.34 (1.42─3.85) .001 Other 4.4% 0.60 (0.21─1.68) .328 0.64 (0.22─1.88) .419 “Data from 1076 PWH regardless of symptoms” Berenguer J, 24TH CROI , Abstract 549, 2021 Del Amo J et al. Ann Intern Med. 2020;173:536-541
  • 20.
    Social and healthdisparities have a color… skin but also passport! Madrid a city of contrasts!
  • 21.
    Does the levelof HIV control affect COVID-19 acquisition among PWH?
  • 22.
    Baseline characteristic Total COVID-19 Case YesaNob RR c 95% CI p-value N (% of total) 15,969 582 (3.6%) 15,387 (96.4%) Nadir CD4+ count (cells/mm3) RR (≤350 vs. >350 cells/mm3) <200 43.1% 44.4% 43.1% 1.17 0.99 ̶ 1.39 0.071 200-349 23.8% 26.7% 23.7% 350-499 15.4% 13.5% 15.5% ref 500 17.7% 15.4% 17.7% CD4+ count (cells/mm3) RR (≤350 vs. >350 cells/mm3) <200 6.5% 6.6% 6.5% 1.04 0.84 ̶ 1.28 0.714 200-349 10.9% 10.7% 110.9% 350-499 15.8% 15.1% 15.8% ref 500 66.9% 67.6% 66.9% ART status 95.2% 95.4% 95.2% 1.02 0.70 ̶ 1.49 0.929 Undetectable viral load (<50 copies/mL) (85.4%) (85.7%) (85.4%) 1.10 0.8 ̶ 1.39 0.424 Data from the CNICS Cohort Shapiro A et al., 24th CROI 2021 abstract 543, 2021
  • 23.
    Risk of diagnosisusing population data from Statewide in New York: March 1 – June 7, 2020 Population size № Diagnosed Rate per 1000 PWH Rate ratio (95% CI) Unadjusted Adjusted CD4 ≥ 500 63712 1774 27.84 1 [ Reference ] 1 [ Reference ] CD4: 200-499 27905 843 30.21 1.08 (0.99─1.18) 1.02 (0.94─1.11) CD4 < 200 7498 270 36.01 1.29 (1.14─1.47) 1.22 (1.07─1.38) Other 8947 101 11.29 NA NA Viral Suppression* Yes 87 480 2628 30.04 1 [ Reference ] NA No 12 027 267 22.20 0.74 (0.65─0.84) NA Other 8555 93 10.87 NA NA Tesoriero J, et al. JAMA Netw Open. 2021;4(2):e2037069. * HIV VL < 200 copies/mL Model adjusted for age, sex, race/ethnicity, HIV transmission risk , region of residence.
  • 24.
    PWH and riskof being diagnosed with COVID-19 • The evidence suggest that PWH have a heterogeneous risk of acquiring SARS-CoV-2 • Those burden by social and structural health disparities and/or have the lowest CD4 Cell count appears to be at the highest risk of infection with SARS-CoV-2.
  • 25.
    Do PWH haveworse clinical outcomes after COVID-19 diagnosis?
  • 26.
    Subsequent population-based cohortstudies have shown a signal worse outcomes Diagnosis Hospitalization ICU/ Mechanical ventilation Mortality
  • 27.
    Summary of 1stwave of studies: No worse outcomes Time Region Design Setting Number Hospitalized ICU Died VL < 200 CD4< 200 Comment Reference 3/30 ─ 5/20 /20 Rhode Island, US Case series Inpt/outp 27 9/27 (33%) 0 1* ALL 1 19 of 27 non-white JIAC 2020, 23:e25573 2/2─ 4/16/20 Milan, Italy Case series Inpt/outp 47 13/47 (28%) 2 2** 44 of 47 0 Good outcome CID 2020;71:2276– 8 3/11─4/17/20 Munich, Germany Cases series Inpt/outp 33 14/33 (42%) 6 3 30 of 32 1 Infection (2020) 48:681–686 3/15─4/15/20 New York, USA Case series Inpatient 31 4 8 (25.8%) ALL 7 ¾ non-whites CID 2020 1:2294–7 2/1─ 4/30/20 Madrid, Spain Cohort Inpt/oupt 51 1.8% (95% CI 1.3–2.3) 28 6 (12%) 2 (4%) ALL 6 follow-up qualitative RT-PCR assays Lancet HIV. 2020;7:e554-564. 3/10─5/11/20 New York, USA Cohort Inpatient 4613 (100 HIV+) ALL HR 1.73 [95% CI: 1.12 to 2.67] HIV+:22% HIV-: 24%) 81 of 90 2/3 non-white No deaths among PWH w/ VL > 200 JAIDS. 2021 1;86:224-230 3/4─4/3/20 New York, USA Matched control (1:2) Inpatient HIV+ 21 HIV- 42 ALL 6 (28.6%) 7 (16.7%) 6 (28.6%) 10 (23.8%) 20 0f 21 1 HIV+ had more non- white JAIDS, 2020;85:6- 10. 3/10─5/15/20 New York, USA Matched control (1:2) Inpatient HIV+ 30 HIV- 90 ALL HIV+ 4 (13%) HIV-21 (23%) HIV+ 2(7%) HIV-14(16%) ALL 7 ¾ non-white OFID. 2020 1;7(8):ofaa327 3/12─4/23/2 New York, USA Matched control (1:5) Inpatient 88 HIV+ 405 HIV- ALL HIV+ 18% HIV- 23% HIV+ 21% HIV - 20% 66 7 ¾ non white CID 2020;71:2933- 2293 3/1─6/21/20 USA (VACS) Matched control (1:2) Inpt/outp POSITIVE HIV+ 253 HIV- 504 HIV+ 86(35%) HIV- 178 (35%) HIV+ 35(14%) HIV- 75 (25%) HIV+ 24(10%) HIV- 56 (11%) More testing but no increased positivity Park L et al. IAC2020 Cachay et al. In Progress
  • 28.
    Among major shortcomings1st wave of initial studies: • Denominator comparison is not accurate: Focus only on those diagnosed and with access to care. • Missed or inaccurate case ascertainment of patients admitted to different health care systems or dying outside care services So let’s review the contribution of the 2nd wave of studies…
  • 29.
    The NC3 Cohort:characteristics of study participants 1 Jan 2020 ̶ 6 Feb 2021 - 39 centers across USA. - ≥ 18 years - RT-PCR positive. Overall N=509,092 PWoH/No SOT N=501,416 PWoH only N=2,932 SOT only N=4,633 PWH & SOT N=111 Age, median (IQR) 46 (31-60) 45 (30-60) 48 (35-59) 57 (46-66) 55 (44-64) Age≥60, N (%) 135,332 (26.6) 132,579 (26.4) 700 (23.9) 2,014 (43.5) 39 (35.1) Male sex, N(%) 230,690 (45%) 225931 (45.1) 1,942 (66.2) 2,745 (59.2) 72 (64.9) Race/ethnicity, N (%) Black Hispanic 825 (0.2) 800 (0.2) ≤20 ≤20 ≤20 Black non-Hispanic 83,910 (16.5) 81,310 (16.2) 1,289 (44%) 1259 (27.2) 52 (46.8) White Hispanic 27,146 (5.3) 26,711 (5.3) 147 (5) 283 (27.2) ≤20 White non-Hispanic 279,923 (55) 276,782 (55.2) 915 (31.2) 2,192 (47.3) 34 (30.6) Others 117,288(23) 115,813 (23.1) 566 (19.3) 889 (19.2) ≤20 (18) Jing S et al. . 24th CROI, oral abstract 103, 2021
  • 30.
    N3C Cohort: Riskof hospitalization according to HIV and SOT status 0 0.25 0.50 0.75 1.00 0 10 20 30 40 Nº at risk 447960 61 1904 2591 PWoH/SOT- PWH/SOT+ PWH alone SOT alone 411794 40 1631 1936 1829 1780 1747 1592 1557 1533 37 37 35 406789 403121 400608 Days since positive covid test Probability of not being hospitalized (%) 9.8% 16.8% 30.1% 39.3% 11.3% 20.1% 33.4% 45.9% PWoH/SOT- PWH/SOT+ PWH alone SOT alone Jing S et al. . 24th CROI, oral abstract 103, 2021
  • 31.
    Hospitalization risk inthe NC3 Cohort comparing PWH with SOT and general population Model a: adjust for age, sex, race/ethnicity, and study site Model b: adjust for age, sex, race/ethnicity, and study site, severe liver disease, DM2, Cancer, renal disease and Nº of comorbidities (0,1,2,≥ 3) Immunosuppression groups Crude estimates Adjusted estimatesa Adjusted estimatesb OR (95% CI) P-value OR (95% CI) P-value OR (95% CI) P-value PWoH & No SOT (n = 501,416) Reference ─ Reference ─ Reference ─ PWH only (n= 2,932) 2.14 (1.99─2.30) < 0.01 1.63 (1.5─1.76) < 0.01 1.32 (1.22─1.43) < 0.01 SOT only (n = 4,633) 4.0 (3.77─4.25) < 0.01 3.07 (2.88─3.27) < 0.01 1.69 (1.58─1.81) < 0.01 PWH & SOT (n= 111) 5.37 (3.57─8.06) < 0.01 3.50 (2.27─5.42) < 0.01 1.65(1.06─2.56) 0.03 Jing S et al. . 24th CROI, oral abstract 103, 2021
  • 32.
    A large nationalUSA Cohort: The TriNetX health research network Yendewa GA et al . 24th CROI, abstract LB 548, 2021 Characteristics PWH ( n =1,638) PWoH (N = 295,556) P Age (mean ± SD) 43.3 ± 13.6 46.5 ± 18.7 <0.001 Male 1137 (69%) 130866 (44%) <0.001 AA or Hispanic 1102 (67%) 100133 (34%) <0.001 CV disease 767 (47%) 77178 (26%) <0.001 Obesity 404 (25%) 43883 (15%) <0.001 - 297, 194 COVID-19 cases > 44 healthcare organizations in US - 1638 PWH (0.6%) > 83% on ART > 48% had HIV VL < 20 copes/mL PWH vs PWoH OR of Hospitalization: 1.26 , 95% CI: 1.04─1.53, p =0.023
  • 33.
    Do HIV viralsuppression and CD4 cell count level impact the risk of hospitalization after COVID-19-diagnosis?
  • 34.
    Population size № Rate per 1000diagnoses Rate ratio (95% CI) Unadjusted Adjusted HIV suppressed 87480 756 287.7 1 [Reference] NA HIV unsuppressed 12027 105 393.3 1.37 (1.11─1.68) NA Other 8555 35 376.3 NA NA CD4≥500 63712 437 246.3 1 [ Reference ] 1 [ Reference ] CD4: 200-499 27905 298 353.5 1.44 (1.24─1.66) 1.29 (1.11─1.49) CD4<200 7498 126 466.7 1.89 (1.55─2.31) 1.69 (1.38─2.07) Risk of hospitalization using population data from Statewide in New York: March 1 – June 7, 2020 Tesoriero J, et al. JAMA Netw Open. 2021;4(2):e2037069. Model adjusted for age, sex, race/ethnicity, HIV transmission risk , region of residence
  • 35.
    Predictors of Hospitalizationamong PWH: IDSA registry of USA and international centers N =286 Characteristics OR ( 95% CI) P-value Age, years 1.08 (1.04─1.07) 0.03 CD4 > 500 Reference ─ CD4 200-500 1.12 (1.1─12.22) 0.03 CD4 < 200 3.67 (1.64─17.1) < .01 CKD 4.08 (1.45─11.52) < .01 COPD 4.06 (1.87─8.81) < .01 HIV with No comorbidity Reference ─ 1-2 comorbidities 1.13 (0.49─2.6) 0.78 ≥ 3 comorbidities 3.57 (1.29─9.9 .01 Dandachi et al, Clinical Infectious disease Nov 2020 Epub Ahead of Print Generalized Estimating Equation (GEE) adjusted models* Model A: The model is adjusted for age, sex, race/ethnicity, years with HIV, CD4 count, HIV viral load suppression, ART regimen, HTN, DM2, COPD, CKD, CV disease, active malignancy, and chronic liver disease Model A Model B Model B: The model for the associations between hospitalization, and the comorbidity burden is adjusted for age, sex, and race/ethnicity.
  • 36.
    Predictors of hospitalizationfor PWH and COVID-19- CNICS Characteristics Not hospitalization N = 160 (81%) Hospitalization N = 38 (19%) RR ( 95% CI) P-value Age ≥ 60 34 (21%) 14 (375) 2.0 (1.13─3.54) 0.017 Female 41 (26%) 13 (34%) 1.02 (0.55─1.88) 0.962 Black vs non-black 77 (48%) 27 (71%) 1.42 (0.69─2.91) 0.336 CD4 ≤ 350 30 (20%) 12 (32%) 1.77 (1.05─2.98) 0.032 On ART 156 (98%) 36 (95%) ─ ─ Undetectable ART 126 (80%) 32 (84%) ─ ─ HCV 20 (13%) 6 (16%) 1.05 (0.48─2.33) 0.900 DM2 33 (21%) 115 (40%) 1.49 (0.85─2.61) 0.166 eGFR < 60 17 (11%) 11 (30%) 1.76 (0.99─3.13) 0.051 BMI ≥ 30 60 (40%) 24 (69%) 1.96 (1.02─3.78) 0.044 COPD 9 (6%) 3 (8%) ─ ─ Shapiro A et al. 24th CROI 2021 abstract 543, 2021
  • 37.
    Adjusted rate ratio(95% CI) 0.5 0.6 0.7 0.8 0.9 1 1.5 2 2.5 3.0 3.5 4 Sex female: 95% CI: 0.87─1.16 Age ≥ 60: 95% CI: 2.66─5.41 Factors associated with hospitalization among PWH─ Data from NYS Adjusted analysis for risk of hospitalization among PWH NYS march 1 to June 7, 2020 Tesoriero J, et al. JAMA Netw Open. 2021;4(2):e2037069. Hospitalization rates per 1000 persons 6229.87 vs 163.86 RR, 1.83 [95% CI, 1.72─1.96) PWH PWoH Models adjusted for age, region of residency, HIV risk factor, CD4 Viral load not included as considered mediator of CD4 and COIVD-19 outcomes 4.5 5 1.01 Black : 95% CI: 0.89─1.48 1.15 3.09 1.11 Hispanic : 95% CI: 0.87─1.43 1.13 MSM + IDU: 95% CI: 0.83─1.53 1.13 IDU: 95% CI: 0.93─1.37 1.29 CD4: 200-499: 95% CI: 1.11─1.49 CD4: <200: 95% CI: 1.38─2.07 1.69 Ref: male Ref: white Ref: MSM Ref: ≥500 1.86 Age 40-59: 95% CI: 1.40─2.46 Ref: < 40
  • 38.
    Comorbidity count ofPWH diagnosed with COVID-19 according to hospitalization status 13% 40% 0% 20% 40% 60% 80% 100% 0 1 2 3 4 5 Hospitalized Not hospitalized Barbera L et al. . 24th CROI, abstract 546, 2021
  • 39.
    Comorbidity count andodds of COVID-19 hospitalization among PWH 0.2 2 20 5+ 4 3 2 1 0.81 1.42 3.19 4.73 6.08 (0.29 ̶ 2.24) (0.49 ̶ 4.09) (1.04 ̶ 9.80) (1.59 ̶ 14.10) (1.93 ̶ 19.15) Comorbidity count Odds Ratio (95% CI) Barbera L et al. . 24th CROI, abstract 546, 2021 N = 180, 97% on ART of whom 91% were suppressed
  • 40.
    Overall, the datasuggest so far that: • PWH have an increased risk (1.3 to 1.5 fold) higher risk of hospitalization than PWoH • The risk is strongly mediated by the number and status of medical comorbidities • Low CD4 cell counts seem to have an independent effect in increasing the risk of hospitalization due to COVID-19 regardless of comorbidity burden • When studies control for comorbidity burden, age and BMI, neither race/ethnicity, HIV risk factor, ART class affect the risk of hospitalization due to COVID-19
  • 41.
    Populations based cohortstudies have shown a signal of worse mortality in HIV patients who acquired COVID-19 in developed and developing countries
  • 42.
    UK: Cumulative mortality:Feb 1 to June 22, 2020 17 282 905 adults were included, of whom 27 480 (0.16%) had HIV recorded. 14 882 COVID-19 deaths occurred during the study period, with 25 among people with HIV HR: 2.90 (95% CI 1.96– 4.30) The association was attenuated, but risk remained high, after adjustment deprivation*, ethnicity, smoking and obesity. Bhaskaran K et al. The Lancet. 2020;8(1):E24-E32. A 0 Feb 1 March 1April 1 May 1 June 1 July 1 Date (2020) .05 .10 .15 100 Cumulative mortality (%) *derived from the patient’s postcode at lower super output area level in the UK adjusted for age, sex only HR: 2.59 (95% CI 1.74– 3.84) HR: 2.30 (95% CI 1.55–3.41) Adjustment for potentially mediating comorbidities reduced the HR slightly
  • 43.
    Western Cape, SouthAfrica: 1 March-9 June 2020 Comparison of adjusted HRs and 95% CIs for associations with COVID-19 death from Cox proportional hazards model 0.7 2 5 40 1 1 2 5 40 0.7 female male 20─39 40─49 50─59 60─69 ≥ 70 No comorbidities A1c < 7% A1c 7─8.9% A1c ≥9% No A1c HTN CKD COPD/Asthma Previous TB Current TB HIV positive female male 20─39 40─49 50─59 60─69 ≥ 70 No comorbidities A1c < 7% A1c 7─8.9% A1c ≥9% No A1c HTN CKD COPD/Asthma Previous TB Current TB HIV positive Age DM2 Age DM2 A. all public-sector patients ≥20 years old with a public-sector health visit in the previous 3 years (n = 3 460 932) B. all adult COVID-19 cases diagnosed before 1 June 2020 (n = 15 203) Boulle A et al, Clinical Infectious disease August 29, 2020 Epub Ahead of Print
  • 44.
    Data from SouthAfrica: Comparison of adjusted HRs and 95% CIs for associations with COVID-19 death from Cox proportional hazards model 0.7 2 5 40 1 1 2 5 40 0.7 female male 20─39 40─49 50─59 60─69 ≥ 70 No comorbidities A1c < 7% A1c 7─8.9% A1c ≥9% No A1c HTN CKD COPD/Asthma Previous TB Current TB HIV positive female male 20─39 40─49 50─59 60─69 ≥ 70 No comorbidities A1c < 7% A1c 7─8.9% A1c ≥9% No A1c HTN CKD COPD/Asthma Previous TB Current TB HIV positive Age DM2 Age DM2 B. all hospitalized COVID-19 cases (n = 2978) A. all adult COVID-19 cases diagnosed before 1 June 2020 (n = 15 203) After adjustment for age, BMI and comorbidities, the independent significant effect on population mortality persisted ~ 1.4 fold Boulle A et al, Clinical Infectious disease August 29, 2020 Epub Ahead of Print
  • 45.
    If hospitalized dueto COVID-19, do PWH have worse clinical outcomes?
  • 46.
    Data from cohortstudies on worse clinical outcomes and mortality: N3C NIH cohort Immunosupression groups Crude estimates Adjusted estimates* OR (95% CI) P-value OR (95% CI) P-value PWoH & No SOT Reference ─ Reference ─ PWH only 1.93 (1.63─2.28) < 0.01 1.73 (1.45─2.06) < 0.01 SOT only 2.66 (2.40─2.96) < 0.01 2.02 (1.81─2.25) < 0.01 PWH & SOT 4.35 (2.54─7.45) < 0.01 3.92 (2.21─6.96) < 0.01 * Model is adjusted for age, sex, race/ethnicity, study site Odds of mechanical ventilation after hospitalization Jing S et al. . 24th CROI, oral abstract 103, 2021
  • 47.
    Predictors of Severeoutcome* among PWH: IDSA registry of USA and international centers N =286 Characteristics OR ( 95% CI) P-value Age, years 1.04 (1.0─1.07) 0.02 CD4 > 500 Reference ─ CD4 200-500 1.93 (0.73─5.06) 0.18 CD4 < 200 2.8 (1.02─7.67) 0.05 HTN 2.43 (1.2─4.93) 0 .01 COPD 3.37 (1.63─6.97) < .01 HIV with No comorbidity Reference ─ 1-2 comorbidities 2.21 (0.42─11.7) 0.35 ≥ 3 comorbidities 5.40 (1.02─28.54 0.05 Dandachi et al, Clinical Infectious disease Nov 2020 Epub Ahead of Print Generalized Estimating Equation (GEE) adjusted models* Model A: The model is adjusted for age, sex, race/ethnicity, years with HIV, CD4 count, HIV viral load suppression, ART regimen, HTN, DM2, COPD, CKD, CV disease, active malignancy, and chronic liver disease Model A Model B Model B: The model for the associations between hospitalization, and the comorbidity burden is adjusted for age, sex, and race/ethnicity. * Severe outcome is defined as a composite outcome of intensive care admission, invasive mechanical ventilation, or death
  • 48.
    IDSA* registry: overallICU and survival curves by CD4 status Overall survival (%) 0.0 0.2 0.4 0.6 0.8 1.0 0 5 10 15 20 25 30 35 0 5 10 15 20 25 30 35 ICU-free survival (%) 0.0 0.2 0.4 0.6 0.8 1.0 + censored Logrank p =0.036 + censored Logrank p =0.05 Time in days Time in days 1 38 37 36 33 33 32 32 32 2 94 92 91 89 89 85 83 81 3 116 116 114 113 112 111 111 110 1 38 29 28 27 27 27 27 27 2 94 87 82 80 79 79 78 78 3 116 108 105 104 103 102 102 102 CD4: < 200 200 ─500 <500 * Includes one site from Spain Dandachi et al, Clinical Infectious disease Nov 2020 Epub Ahead of Print
  • 49.
    CoVIH-19 Study across39 centers in Spain “HIV Infection was associated with higher incidence of death” ( N = 204 ), Feb 26 ̶ Sept 21, 2020 Competing-risks regression analysis Cumulative incidence 0.02 0.04 0.06 0.08 0 0 10 20 30 Days after admission subHR 3.45, 95% CI 1.47 ─8.11, p =0.0045 PWH PWoH The risk of death remain but less strong decreased after adjustment for liver disease, CV and obesity aOR: 5.27 CI 1.00 ─ 27.72, p =0.049 ART: NNRTI 17%, PI: 23%, INSTI: 70%, 89% NRTI (6% TDF, 45% TAF, and 31% ABC) Mortality among PWH was not associated with: Current or Nadir: CD4, CD4/CD8 ratio Detectable HIV RNA Specific ART agent (TDF/TAF)) Blanco JL et al . 24th CROI, abstract 641, 2021.
  • 50.
    Trends at UCSan Diego Health Outcomes PWH, N (%) Non-PWH, N (%) Positive aOR* (95% CI) At risk patients 3,609a 235,609a Hospitalization 16 (15%) 76 (13%) ICU 6 (6%) 26 (4%) 1.33 (0.44, 3.96) Intubation 6 (6%) 10 (2%) 2.35 (0.62, 8.96) Death 2 (2%) 11 (2%) 3.04 (0.46, 19.94) *Adjusted Odds Ratio for age, gender, race/ethnicity, diabetes, and obesity and other covariates via backwards model selection a. Percentage of all patients with established primary care at UCSD Tang Michael, Gaufin T, Anson R et al . 24th CROI, abstract 542, 2021.
  • 51.
    Are there specialconsiderations for SARS- CoV-2 immune responses in PWH?
  • 52.
    Data from UCSF:Match 1-2 outpatients PWoH based on age (+/- 5 years) and date of collection IgG levels by HIV status among those with reactive SARS-CoV-2 IgG Relative Fluorescent Units (Mean ± 1 SE; log10 scale) PWoH N = 70 PWH N = 31 Neutralizing Ab titers: 63% (95% CI: 2%─78% lower) lower among PWH vs. PWoH with past infection Avidity: No difference (+7.9%; 95% CI: -4%─ +20%) Unknowns: - Proportion of asymptomatic and hospitalized between groups comparable - Median CD4 of PWH 1000 300 100 45% lower 95% CI: 22%─61% Spinelli M al. 24th CROI, abstract 627, 2021
  • 53.
    Data from MiamiCFAR: “All symptomatic outpatients” PWH N = 17 PWoH N = 19 PWH N = 17 PWoH N = 19 “All PWH had viral load < 500 copies./mL and a median CD4: 859” IgM PWH vs PWoH IgM PWH vs PWoH T1 = W2 T2 = W4 T3 = W12 *Ab units based on the positive control standard IgM (relative titer*) IgG (relative titer*) Alcaide M et al. 24th CROI, abstract 260, 2021 20000 40000 60000 500000 1000000 1500000 2000000 Cut-off 54234 0 T0 T1 T2 T3 T3 T2 T1 T0 Cut-off 12646 T0 T1 T2 T3 T0 T1 T2 T3 0 5000 10000 15000 20000 1000000 2000000 3000000 4000000 5000000
  • 54.
    Data from Oxford:Serology and T cell response assessment Median range CD4 560 (133─1360 CD4:CD8 0.87 (0.17─2.54) All PWH had viral load < 50 copies/mL 76.6% (n=36) Mild 19.2% (n=9) moderate (hospital) 4.3% (n= 2) asymptomatic 74.2% (n=26) Mild 11.4% (n=4) moderate (hospital) 14.3% (n= 5) asymptomatic PWH PWH N = 47 PWoH N = 35 PWoH Convalescent phase 148 (46-273) 146 (101-220) PWH PWoH Days post-symptom onset 80 60 40 20 Age (years) 0 0 100 200 300 Alrubayyi At et al. 24th CROI, abstract 262, 2021
  • 55.
    Comparable Ab levelswith neutralizing activity among PWH and PWoH S1 IgG Titer mg/mL N IgG Titer mg/mL ID 50 neutralization titer Asymptomatic Non hospitalized Hospitalized PWoH PWH 0.1 1 10 100 PWoH PWH 100 10 1 0.1 PWoH PWH 10 100 1000 10000 Detection Limit Minimum ID50 Potent Alrubayyi At et al. 24th CROI, abstract 262, 2021
  • 56.
    SARS-Cov-2 INF-g T-cellElispot responses did not differ by HIV status ∆ 5FU/ 10 6 PBMCs % of specific T cells CD4 T cell cytokines preferentially reacted with spike or membrane/nucleocapside proteins regardless of HIV status ns ns ns PWoH PWH 100 10 1000 1 *** * PWoH PWH 0.0 0.5 1.5 1.0 CD4 CD4 CD4 CD4 CD8 CD8 CD8 CD8 Spike Spike M/N M/N *** ** Alrubayyi At et al. 24th CROI, abstract 262, 2021
  • 57.
    SARS-Cov-2 specific T-cellresponses correlate with the CD4:CD8 ratio and % naïve CD4T Cells in PWH CD4:CD8 ratio Total SARS-CoV-2 T Cells ∆ 5FU/ 10 6 PBMCs r =0.3820 p=0.037 r =0.5518 p=0.0143 0 1 2 3 0 200 400 600 Total SARS-COV-2 T cells ∆ 5FU/ 106 PBMCs 100 200 300 400 0 0 20 40 60 80 % of naïve CD4 T cells CCR7+ CD45RA+ Alrubayyi At et al. 24th CROI, abstract 262, 2021
  • 58.
    Conclusions - The riskof COVID-19 acquisition is likely influence by structural social and health disparities, prevalent among PWH rather than a strong biological effect. - PWH with high burden of comorbidities and/or have low CD4 cell count seem to have an increase risk of hospitalization. - PWH tend to have worse clinical outcomes reflected by increased frequency of ICU admission and mechanical ventilation than PWoH - PWH have ~ 1.3 to 1.5 increased mortality due to COVID-19 not fully explained by BMI, age, and comorbidity burden. Unaccounted confounders? Oversimplification/correction? - Most PWH mount a good antibody response to SARS-CoV-2 similar than PWoH, however, PWH with low CD4:CD8 ration could have compromise immune response to SARS-CoV-2
  • 59.
    “ Education isthe most powerful tool to change the world, and it should not be a privilege of some but a right for all” ̶ Edward Cachay # zerosexism #zerohate # zerodiscrimination

Editor's Notes

  • #11 55K PWoH and 5.6 million PWH
  • #19 Race/ethnicity and poverty distribution according to COVID-19 diagnosis status 1. Evidence of sginifcant disparities: Overall 86.1% of PWH with COVID-19 identified as Black or Latino/Hispanic compared with 78. of PWH without COVID-19 and 33% of all NYC COVID-19 cases
  • #20 Julia del Amo; COHORT study in 60 clinics in Spain showed that after excluding HWC positive rae was comparable in PWHa nd PWoH. Hoever they only adjusted for x and age, No data on comrobity, and other social determinants So Juan berenguer looked a serology in CORiS cohort in Spain. And showed that regardless of symptms risk as not the same in all HIV patients.
  • #24 Viral suppression is not included in multivariable models with stage of HIV infection, since viral suppression is a likely mediator of the association between HIV stage and COVID-19 outcome
  • #30 National Cohort Collaborative, is a NIH funded
  • #31 39 centers across USA. ≥ 18 years RT-PCR positive.
  • #36 Multicenter registry: The greatest percentage of patients in the USA was from the South (47.0%), followed by the, Northeast (35.4%), Midwest (5.3%), and West (4.9%); 7.4% were from international locations.
  • #38 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]).
  • #39 Study done Emory. N = 180. 91% HIV VL < 200. CD4: median 527, 92% either Black (78%0 or LAtinX (145%
  • #40 Age-adjusted OR (95% CI) for each additional comorbidity with COVID-19 hospitalization No association with hospitalization and HIV parameters when analysis was restricted to CD4 < 200 or HIV RNA ≥ 200
  • #44 Among ~ 3,5 million patients (16% HIV positive), 22,308 were diagnosed with COVID-19, of whom 625 died
  • #45 They did not observe effect on HIV viremia or CD4 count status affecting outcome The reported E-values on the study to assess whether the association between HIV and COVID-19 mortality could not rule out that it could be due to residual unmeasured confounding e.g. by socio-economic status, or unrecorded comorbidities
  • #48 Multicenter registry: The greatest percentage of patients in the USA was from the South (47.0%), followed by the, Northeast (35.4%), Midwest (5.3%), and West (4.9%); 7.4% were from international locations.
  • #50 Each case wat matched 1:1 to control (COVID-19 confirmed PWoH) matched for center, Week (+/- 5 days), age and gender 90% suppressed 14% CD4 < 20
  • #54 In-house ELISA to measure EBD of spike protein
  • #55 Step 1: assess serology response. ELISA spike protein Step 2: T cell response 2.1: SARS CO-2 T Cells ( ELiSPot) 2.2. Intracellular staining of T cells: phenotypic characterization
  • #57 Left: Most of donors have cells response against spike protein in membrane or nucleocapside. The overall response did not differ between the two groups RIGHT: At the individuals with a T Cell Elipsot response they look at the composition and polyfunctionality of T cells responses. Thye look at cytokine specific responses. CD4 T cell cytokine staining were gins Spike and Nucleopcapside were more frequent regardless of HIV status
  • #58 Incomplete immune reconstitution reflected by lower CD4:CD8 ratio or naive CD4 cell count could comprise response and immunity to SARS-CoV2