HIV-Associated Neurocognitive Impairment in Hispanics/Latinos in the US Maria J. Marquine 11/30/2018 UCSD HIV & Global Health Rounds

2. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
HIV-Associated Neurocognitive Impairment
among Hispanics/Latinos in the US
María J. Marquine, Ph.D.
Assistant Professor
Department of Psychiatry
University of California San Diego
HIV and Global Health Rounds
November 30th, 2018

3. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
Disclosures
§ No conflicts of interests

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Outline
§ Hispanics/Latinos in the United States
§ Hispanics and HIV
§ HIV-associated Neurocognitive Impairment
§ HIV-associated Neurocognitive Impairment among Hispanics
§ Summary/Implications
§ Ongoing Work/Future Directions

5. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
Hispanics in the U.S.

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Who is Hispanic or Latino/a?
Hispanic
Latino/a

7. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
Understanding the terms Hispanic, Latino/a, Latinx
§ Hispanic is a person who traces his/her roots to Spanish-
speaking nations from Latin America and Spain itself (but
not Portuguese-speaking Brazil).
§ Latino/a is a person from Latin America (includes Brazil).
§ Latinx is a gender neutral word for persons of Latin
American descent (related term: Latin@)

8. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
Who is Hispanic or Latino in the U.S.?
§ Who is Hispanic/Latino according to the U.S. Office of
Management and Budget?
» Persons who trace their origin or descent to Mexico, Puerto Rico,
Cuba, Spanish speaking Central and South America countries, and
other Spanish cultures.
» Origin can be considered as the heritage, nationality group,
lineage, or country of birth of the person or the person's parents or
ancestors before their arrival in the U.S.
» People who identify their origin as Hispanic or Latino may be of any
race.

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Hispanics in the U.S. by the Numbers
§ 57.5 million Hispanics in the U.S., largest ethnic/racial minority
group (17.8% of the population)
§ Hispanics by country of origin/descent
» 63% Mexican; 9% Puerto Rican; 4% Cuban
§ Language use:
» 72% of Hispanics (age 5 and older) speak Spanish at home (58% of
those also speak English)
§ Place of Birth
» 34% of Hispanics are foreign born
§ States with largest numbers of Hispanics:
» California (15.3 million), Texas (10.9 million), Florida (5.1 million)
» Other states with over 1 million: New York, Illinois, Colorado, New
Jersey, New Mexico, Arizona
U.S. Census Bureau (2017)

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Hispanics and HIV

11. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
Adults/Adolescents Living with Diagnosed HIV Infection by
Race/Ethnicity (2015—United States)
1017.8
379.4
160.3 150.9 122.6
74.8
0
200
400
600
800
1000
1200
Black Hispanic Pacific
Islander
White American
Indian
Asian
Rateper100,000
HIV Surveillance Report (2016). CDC.

12. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
HIV Disease Worse among Hispanics
§ Hispanics tend to present with reduced healthcare use and
access, and higher HIV disease burden.
» HIV+ Hispanics less access to care1.
» HIV+ Hispanics are at greater risk for delayed care and
diagnosis than Whites2, 3.
» HIV+ Hispanics lower CD4 counts, higher plasma viral loads,
more opportunistic infections4.
» Differences among subgroups of Latinos by country/region
of birth5.
1Shapiro et al. (1999) JAMA; 2Dennis et al (2011) CID; 3Chen et al. (2012) J Immigrant and Minority Health;
4Swindells et al (2002) AIDS; 5Sheehan et al (2015) Int J STD AIDS.

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HIV-Associated Neurocognitive
Impairment (NCI)

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Focus on Brain Health
§ Many changes with HIV
» Physical
» Social
» Emotional
» Neurocognitive

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HIV-Associated Neurocognitive Impairment (NCI)
1Heaton et al (2011). JNV; 2Antinori, et al (2007). Neurology; 3Heaton et al (2004). JINS
• The adverse consequences of HIV on the central nervous
system (CNS) remain prevalent in the era of antiretroviral
therapy
• ~40% of HIV+ persons show neurocognitive impairment (NCI)1
• HIV-associated NCI is typically mild2; but is associated with
poor everyday functioning3

16. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
HIV-Associated Neurocognitive Impairment (NCI)
0%
10%
20%
30%
40%
50%
60%
70%
Verbal SIP Learn Recall Attn/WM Exec Motor
PercentImpaired Pre-CART Post-CART
** ***
***
*
**
*p<.05; **p<.01; ***p<.001 Heaton et al (2011). JNV
• Although Hispanics are at increased risk for adverse health outcomes in
HIV, few studies have investigated HIV-associated NCI in this group1-4
1
Marquine et al (2017). JINS; 2
Rivera et al (2008). Cul Div Ethn Min Psych; 3
Rivera et al. (2014) Beh Med; 4
Wojna et al (2006) JNV.

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NCI in HIV+ Puerto Rican Women
§ Participants: 49 HIV+ women living in Puerto Rico with nadir CD4
counts <500 cells/mm3
(Age M=36.7, SD=6.3; Educ M=12.0, SD=2.0)
§ Neurocognitive
Battery
§ Results: 77.6% NCI
§ 33% mild (asymptomatic NCI); 16% moderate (minor cognitive motor
disturbances); 29% severe (HIV-associated dementia-HAD)
Wojna et al. (2006). JNV
Cognitive Domain Test
Psychomotor Speed Digit Symbol Modality Test
Verbal Memory Rey Auditory Verbal Learning Test
Frontal Executive Stroop; Trail Making Test B
Motor Speed Trail Making Test A
Visuoconstruction Cube

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NCI in HIV+ (Caribbean) English-Speaking Hispanics
§ Participants:
» HIV+ from Manhattan HIV Brain Bank (advanced stage of disease)
» 51 (Caribbean) English-Speaking Hispanics and 49 non-Hispanic Whites
» Age: M=44.5, SD=7.4; Education: M=12.9, SD=2.4; 78% men
§ Neurocognitive
Battery
Rivera-Mindt et al. (2008). Cultur Divers Ethnic Minor Psychol
Cognitive domain Tests
Verbal Functioning FAS
Speed of Information
Processing
WAIS-III Digit Symbol, WAIS-III
Symbol Search, TMT-A
Learning HVLT & BVMT Total Correct
Delayed Recall HVLT & BVMT Delayed Recall
Attention/Working Memory WAIS-III Letter-Number;
PASAT
Abstraction/Executive
Function
WCST – 64, TMT-B
Motor Grooved Pegboard

21. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
NCI in HIV+ (Caribbean) English-Speaking Hispanics
§ Results
» Among HIV+ Hispanics: 70% impaired (TS<40)
• 28% mild, 36% mild to moderate, 31% moderate, 6% severe
Variable Global TS
Β (p)
Learning TS
Β (p)
Att/WM TS
Β (p)
Abstraction/EF TS
Β (p)
Hispanic
Ethnicity
-.12 (.30) -.06 (.59) -.11 (.34) -.33 (.01)
SES -.18 (.11) -.06 (.54) -.08 (.47) -.21 (.08)
WRAT-3 .43 (<.001) .49 (<.001) .43 (<.001) .15 (.18)
CD4 count .08 (.41) .08 (.38) .05 (.58) .03 (.78)
Predictors of neurocognitive performance in HIV+
Rivera-Mindt et al. (2008). Cultur Divers Ethnic Minor Psychol

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HIV/aging: NCI in HIV+ (Caribbean) English-Speaking Hispanics
§ Participants
» HIV+ from NYC
» 84 Hispanic and 42 non-Hispanic
» Exclusion criteria: Notable psychiatric or medical comorbidity
§ Neurocognitive
Battery
Cognitive domain Tests
Verbal Functioning FAS; Animal Fluency
Abstraction/Executive
Function
WCST – 64, TMT-B, Iowa
Gambling Task
Speed of Information
Processing
WAIS-III Digit Symbol, WAIS-III
Symbol Search, TMT-A
Attention/Working Memory WAIS-III Letter-Number;
PASAT
Learning HVLT & BVMT Total Correct
Delayed Recall HVLT & BVMT Delayed Recall
Motor Grooved Pegboard
Rivera-Mindt et al. (2014). Behavioral Medicine

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42.93
46.83
41.48
40.49
30
32
34
36
38
40
42
44
46
48
50
Younger Older
GlobalNeurocognition(TS)
HIV+ NH White
HIV+ Hispanic
HIV/aging: NCI in HIV+ (Caribbean) English-Speaking Hispanics
*
n=20 n=62 n=22 n=22
Rivera-Mindt et al. (2014). Behavioral Medicine
*p=.054

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26. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
NCI in HIV+ English-speaking Hispanics in the US
§ Participants
» HIV+ from CHARTER study (academic medical centers across U.S.)
» 194 English-Speaking Hispanics; 600 NH Whites
§ Neurocognitive
Battery
Cognitive domain Tests
Verbal Functioning FAS; Animal Fluency
Speed of Information
Processing
WAIS-III Digit Symbol, WAIS-III
Symbol Search, TMT-A
Learning HVLT & BVMT Total Correct
Delayed Recall HVLT & BVMT Delayed Recall
Attention/Working Memory WAIS-III Letter-Number;
PASAT
Abstraction/Executive
Function
WCST – 64, TMT-B
Motor Grooved Pegboard
Marquine et al (2017). JINS

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Study Cohort by Ethnic Group
Variable Whites (n=600) Hispanics (n=194)
Demographics
Age, M(SD) 43.07 (9.14) 41.33 (8.14)
Education, M(SD)*** 13.39 (2.69) 12.50 (2.77)
Gender (% Male)** 87.83% 78.35%
Major Genetic Ancestry (%)a ***
Europe 100% 64.57%
Africa 0% 11.81%
American Indian 0% 3.94%
East Asian 0% 0.79%
No Single Major Ancestry 0% 18.90%
a Major genetic ancestry = genetic ancestry proportion of ≥.5 for a given region (Africa,
Europe, America, East Asia, Central Asia, and Oceania), all frequencies <.5 = “no single
major ancestry”; Whites: n=419; Latinos: n=127
*p<.05; **p<.01; ***p<.001

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HIV Disease Characteristics by Ethnic Group
Variable Whites (n=600) Hispanics (n=194)
% AIDS* 51.84% 60.53%
Estimated duration of infection (years),
M(SD)
9.44 (6.72) 9.99 (6.57)
Current CD4, Median (IQR)** 471 (315, 647) 402 (258, 585)
Nadir CD4, Median (IQR)* 192 (60, 317) 150 (40, 281)
On ART 69.28% 76.09%
% detectable plasma ** 39.15% 53.62%
% detectable CSF * 9.12% 18.02%
Months exposure to ART, Median (IQR) 48.59 (6.67, 96.98) 59.33 (8.53, 97.05)
*p<.05; **p<.01; ***p<.001
Marquine et al (2017). JINS

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Comorbidities by Ethnic Group
Variable Whites (n=600) Hispanics (n=194)
VACS Index, Median (IQR) 15 (7, 24) 16 (10, 27)
Comorbidity Status (%)
Incidental 61.27% 52.63%
Contributing 26.21% 32.11%
Confounding 12.52% 15.26%
Psychiatric Characteristics
Beck Depression Inventory, M(SD) 14.93 (11.19) 14.10 (9.88)
Current Major Depressive Disorder 16.78% 16.23%
Lifetime Major Depressive Disorder * 59.30% 50.79%
Current Any Substance Use Disorder 4.19% 3.66%
Lifetime Any Substance Use Disorder 72.53% 67.02%
Intravenous drug use ever 26.67% 25.26%
Urine toxicology positive 12.75% 16.67%

30. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
NCI by Ethnic Group
42
21
40
23
44
40
26
32
54
24
51
30
54
49
40
31
0
10
20
30
40
50
60
Global Verbal
Fluency
Executive
Dysfunction
Speed of
Information
Processing
Learning Recall Working
Memory
Fine Motor
Skills
NeurocognitiveImpairment(%)
NH White (n=600)
Hispanic (n=194)** **
*
* *
**
Marquine et al (2017). JINS
• Ethnic differences in NCI (global and most domains) remained significant after adjusting for
significant covariates (HIV disease characteristics and comorbidities).
• Nadir CD4 was the only significant partial mediator of differences in global NCI.
*p<.01; **p<.001

31. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
NCI by Hispanic Subgroup
0
10
20
30
40
50
60
70
80
Global
Cognition
Verbal
Fluency
Executive
Function
Speed of
Information
Learning Memory Working
Memory
Fine Motor
Skills
NeurocognitiveImpairment(%)
Mexican (n=79) Puerto Rican (n=60)
** ** *
• Differences in domain and global NCI remained significant after adjusting for significant
covariates.
• Comorbidity status was the only significant partial mediator of differences associated with
country of origin.
Marquine et al (2017). JINS

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NCI By Hispanic Subgroup and Site
33
54
47
79
0
10
20
30
40
50
60
70
80
90
San Diego New York
PercentGlobalNCI
Study Site
NH White
HispanicMexican
PuertoRican
Logistic regression on global NCI showed:
• Significant main effects of Hispanic ethnicity (OR = 2.31, p<.001) and NY
site (OR = 2.83, p<.001), and no significant interaction (p=.35).

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In a model adjusting for characteristics that differed significantly
between groups:
Hispanic - NH White: OR=2.8, CI=1.4-5.6, p<.001
Hispanic - NH Black: OR=3.2, CI=1.6-6.3, p<.001
Neurocognitive Decline by Ethnic/Racial Group
*p<.05
19 20
40
0
5
10
15
20
25
30
35
40
45PercentNeurocognitive
Decline
Ethnic/racial group
NH White (n=185)
NH Black (n=184)
Hispanic (n=57)
Watson et al (In preparation)

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The Veterans Aging Cohort Study (VACS) Index and NCI
34.3 35.4
57.3
0
10
20
30
40
50
60
70
Low Mid High
PercentwithNCI
VACS Index
The VACS Index combines1-4:
• Age
• Traditional HIV biomarkers (current
CD4 count and HIV-1 plasma RNA)
• Non-HIV biomarkers (renal and liver
function, anemia and hepatitis C)
Marquine et al (2014). JAIDS. Marquine et al (2016). CID
1Justice (2010). Curr HIV/AIDS; 2Justice et al. (2012). CID; 3Tate et al. (2013). AIDS; 4Justice et al. (2013). JAIDS.
0 1 2 3 4 5 6
0.00.20.40.60.81.0 Years
PredictedProportionof
ParticipantswithoutNCI
VACS
Lower 25%
Middle 50%
Upper 25%

35. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
VACS Index and NCI by Ethnic/Racial Group
Marquine et al (2015). Journal of NeuroVirology

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Summary/Implications
§ HIV+ Hispanics appear to be at increased risk for NCI compared
to HIV+ non-Hispanic Whites
» Most of the work has been done in English-speaking Hispanics
» Some subgroups of Hispanics might be particularly vulnerable to NCI
(older age, Caribbean descent)
§ Given the impact of NCI on everyday functioning, particularly
important to screen for NCI among HIV+ Hispanics
§ Key factors underlying ethnic disparities in HIV-associated NCI
and predictors of NCI within HIV+ Hispanics are not well-
understood
§ Identifying predictors of NCI among Hispanics might enhance
the development of culturally-targeted interventions aimed at
reducing HIV-related ethnic disparities in NCI

38. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
Ongoing Work: Metabolic Syndrome and
HIV-associated NCI

39. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
Understanding Mechanisms Underlying Ethnic
Disparities in HIV-Associated NCI

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Acknowledgements
§ Study Volunteers and Staff
§ Research Collaborators
§ Robert Heaton, PhD; Mariana Cherner, PhD; David J. Moore,
PhD; Ron Ellis, MD, PhD; Scott Letendre, MD
§ K23 MH105297
§ R25 MH080663
§ R01 MD013502
§ CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER)
» N01 MH22005, HHSN271201000036C, HHSN271201000030C
§ HNRP Group
» P30MH062512, U24MH100928, U01MH083506, R24MH59745,
P01DA12065

41. HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGOHIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO
Thank you
for your attention
María J. Marquine, PhD
mmarquine@ucsd.edu