Edward Cachay, MD, MAS Professor of Medicine Division of Infectious Diseases & Global Public Health Department of Medicine University of California, San Diego

1. 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.

2. Making sense of the COVID-19
data in Persons with HIV
Edward Cachay MD, MAS
Professor of Clinical Medicine
University of California, San Diego

3. • 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

4. 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’)

5. 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

6. Courtesy of Captain Rene 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 being tested for SARS-CoV2
in a similar proportion to PWoH?

9. 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.

10. 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

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 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

13. Do PWH have an increased
susceptibility to SARS-Co-V2?

14. 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

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 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.

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 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%

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 health disparities have a color… skin but
also passport!
Madrid a city of
contrasts!

21. Does the level of HIV control affect COVID-19
acquisition among PWH?

22. 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

23. 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.

24. 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.

25. Do PWH have worse clinical outcomes
after COVID-19 diagnosis?

26. Subsequent population-based cohort studies
have shown a signal worse outcomes
Diagnosis
Hospitalization
ICU/
Mechanical
ventilation
Mortality

27. 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

28. 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…

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: 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

31. 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

32. 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

33. Do HIV viral suppression and CD4 cell count
level impact the risk of hospitalization after
COVID-19-diagnosis?

34. 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

35. 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.

36. 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

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 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

39. 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

40. 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

41. Populations based cohort studies 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, 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

44. 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

45. If hospitalized due to COVID-19, do
PWH have worse clinical outcomes?

46. 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

47. 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

48. 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

49. 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.

50. 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.

51. Are there special considerations 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 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

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 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

56. 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

57. 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

58. 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

59. “ 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