Estimating burden of disease among aging HIV-infected individuals in LMICs

Annette H. Sohn, MDTREAT Asia/amfAR – ThailandAIDS 2014

HIV as a Chronic Disease

• Life expectancy estimates improving with earlier ART and immune recovery1

– Low CD4 the dominant predictor across high- to low-income settings

• With constant treatment expansion in SSA – 2011: 1 in 7 PLHIV >50 years 3.1M2

– 2040: 1 in 4 PLHIV >50 years 9.1M• Prevalence in South Africa 17%3

1. Sabin CA, BMC Medicine, 2013;11:251.2. Hontelez JAC, AIDS, 2012;26:S19-30. SSA=Sub-Saharan Africa3. Hontelez JAC, AIDS, 2011;25:1665-7.

Aging and mortality, South Africa 2004-12+

• 5,00010,000 patients in 6 cohorts– 610% >50 years old at enrollment– 220% >50 year-olds in care 1

6-2

9

30

-34

35

-39

40

-44

45

-49

50

-54

55

-59

60

-64

65

+

0

0.1

0.2

0.3

0.4

Age, years

5-year cumulative mortality hazard

HIV-negative

HIV-positive

Cornell M, IeDEA Southern Africa. In submission.

How do HIV and ART modify NCD risk?

• Causes of death increasingly related to non-AIDS events– Veterans’ Aging Cohort Study (VACS): PLHIV

with increases in adjusted incidence of myocardial infarction (81%), end-stage renal disease (43%), and AIDS-related cancers (84%)*

*Althoff K, CROI 2013, #59. Cancers: Lung, liver, anal, oropharyngeal, Hodgkins lymphoma.

Inflammation↑ Monocyte activation

↑ T-cell activationDyslipidemia

Hypercoagulation

Microbial translocation

HIV-associated fatmetabolic syndromeHIV production

HIV replication

CMVExcess pathogens

Loss of regulatory cells

Co-morbiditiesAging

Slide courtesy of Steve Deeks, University of California, San Francisco.

NCDs

Cardiovascular

Stroke

Renal

BoneMetabolic

Pulmonary

Cancers

LiverMental, neurologic

Challenges in Estimating Burden of NCDs in LMICs

• Data sources frequently clinic-based, cross-sectional or short-term– Few registries linking HIV to NCDs

• Risk assessment methods frequently based on Western patient data– Framingham, D:A:D, VACS Index, eGFR

• Lack HIV-negative comparator group– Difficult to separate out impact of HIV, ART

Cardiovascular Disease

• Incomplete ascertainment of CV events and causes of death for general and HIV-positive populations in LMICs*

• Risk may decrease for some conditions and increase for others after ART– Thailand: metabolic syndrome higher among

ART-experienced (25%) vs. naive (16%) or general population (13%)**

*Hertz JT, PLoS One. 2014 May 9;9(5):e96688.**Jantarapakde J, AIDS Patient Care STDS. 2014 Jun 10. N=580, national study.>3 of: abdominal obesity, hypertriglyceridemia, low HDL, high blood pressure, high fasting plasma glucose (AHA and NHLBI criteria).

Primary Cardiovascular Diagnoses Among PLHIV, Heart of Soweto Study

Silwa K, Eur Heart J. 2012 Apr;33(7):866-74. N=518

HypertensionData period

Sample size

HTN rate Reference

KenyaHIV+ only, 66% on ART

2006-2009 12,194 11.2% men, 7.4% women

Bloomfield GS, PLoS One. 2011; 6(7):e22288.*

South AfricaHIV+ only

2004-2011 17,378 29% at ART start, 17% at 24 months

Brennan AT, CROI 2014, #759.*

Asia, regionalHIV+ only, all on ART

2010-2013 5741 21% at last BP50% at any BP

TREAT Asia-TAHOD

Uganda, General survey, 8% HIV+

2011 2278 27% men, 29% women

Chamie G, PLoS One. 2012;7(8): e43400.*

Tanzania and UgandaGeneral survey, 10-11% HIV+

2012-2013 1984 16.5% Tanzania, 25% Uganda

Kapiga SH, CROI 2014, #1016.

*HTN defined as SBP >140, DBP >90.

Yanik EL, Clin Infect Dis, 2013 Sep;57(5):756-64. CNICS=Centers for AIDS Research Network of Integrated Clinical Systems

Incidence of First Cancer after ART CNICS, 1996–2011

Age

-sta

ndar

dize

d ra

te, c

ases

per

100

,000

Incidence of KS on ARTSetting Data period Sample size Incidence per

100,000 PYReference

Caribbean, Central/South AmericaCCASAnet

2007-2009 3372;8080 PY

450 Fink VI, J Acquir Immune Defic Syndr, 2011 Apr 15;56(5):467-73.

East Africa IeDEA

2008-2011 98,024; 144,182 PY

201 in Uganda 270 in Kenya

Martin J, Infect Agent Cancer, 2012;7S1:O19.

IeDEA South Africa

2004-2010 17,516; 30,352 PY

138 Bohlius J, Int J Cancer, 2014 Apr 12.

IeDEA Southern Africa

2004-2010 173,245; 316,787 PY

173 In submission

US, CNICS 1996-2011 11,485;46,318 PY

304 Yanik EL, Clin Infect Dis, 2013 Sep;57(5):756-64.

Adapted from Semeere AS (Curr Opin Oncol 2012;24:522-30) and Rohner E (in submission).

Hepatic Decompensation and Death in HIV-HCV vs. HCV Patients

VACS-VC: Standardized cumulative incidence of decompensation higher among co-infected (7.4%) vs. mono-infected (4.8%) patients at 10 years – even if no/minimal fibrosisLo Re V 3rd, Ann Intern Med. 2014 Mar 18;160(6):369-79.

French National Hospital Database: Overall mortality higher for co-infected (7.5%) vs. monoinfected (2.8%) patients; No difference among those with HIV-HBV.Mallet V, CROI 2014, #690.

Liver Disease

• Zambia: 8.5% of patients entering HIV care with fibrosis by FIB-4 and APRI (N=35,551)1

• Thailand: 11% of HBV/HCV-negative ART patients with liver stiffness by FibroScan® (N=585)2

– 21% >50 years old; median time on ART 11 years

• TREAT Asia HCV treatment eligibility study3

– Viral load (N=184): 83% detectable HCV, median (IQR) 1,954,051 (482,000-4,332,188) IU/mL

– FibroScan® (N=120): 33% F1, 22.5% F2, 24% F3, 20% F4

1. Vinikoor MJ, CROI 2014, #790. Significant fibrosis defined as FIB-4 >3.25 or APRI >1.5.2. Avihingsanon A, CROI 2014, #786. Abnormal result >7.2kPa.3. Durier N, AIDS 2014, TU11263LB. Metavir fibrosis scores: F1-mild, 2-moderate, 3-severe, 4 cirrhosis.

Summary

• Improved diagnostic capacity and reporting systems in LMICs are needed to reliably estimate NCD burden – Service integration with HIV infrastructure?– National health surveys, regional cohort studies,

cancer registries

• Risk factor data can help distinguish HIV- and non-HIV-related outcomes and target screening recommendations– Traditional NCD and HIV-specific exposures

Acknowledgements

• Amy Justice, VA Connecticut Healthcare System• Jintanat Ananworanich, MHRP• Paolo Miotti, NIH OAR• IeDEA Southern Africa – Julia Bohlius, Morna

Cornell, Gilles Wandeler, Mary-Ann Davies, Matthias Egger

• Kirby Institute – David Boettiger, Awachana Jiamsakul, Matthew Law