Reducing AIDS-Related Death in Asia-Pacific: What We Know and What We Need to Do Somnuek Sungkanuparph, M.D. Professor of Medicine Division of Infectious Diseases, Department of Medicine Faculty of Medicine Ramathibodi Hospital, Mahidol University Somnuek Sungkanuparph, M.D. Professor of Medicine Division of Infectious Diseases, Department of Medicine Faculty of Medicine Ramathibodi Hospital, Mahidol University What We Know and What We Need to Do Global HIV Trends, 1990-2011 Change in incidence rate among adults 15-49 years old Rank Opportunistic Infection Number % 1 Tuberculosis 79559 29.61 2 PCP 57235 21.3 3 Cryptococcosis 43339 16.14 4 Invasive candidiasis 14202 5.29 Opportunistic Infections in Thailand Total = 268,706 AIDS patients reported in 1984-2005 Source: MOPH 5 Recurrent pneumonia 10070 3.75 6 Cerebral toxoplasmosis 8006 2.98 7 Penicilliosis marneffei 6709 2.5 8 AIDS dementia complex 4155 1.55 9 MAC 2597 0.97 10 Chronic herpes simplex infection 2448 0.91 25 30 35 40 45 Percentage Causes of Death among AIDS in Thailand 0 5 10 15 20 25 TB PCP Crypto CMV MAC Toxo PML AIDS patients reported in 1984-2005 Source: MOPH Research Centre for Health Economics and Evaluation (ReCHEE)
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Reducing AIDS-Related Death in Asia-Pacific:
What We Know and What We Need to Do
Somnuek Sungkanuparph, M.D.
Professor of Medicine
Division of Infectious Diseases, Department of Medicine
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Somnuek Sungkanuparph, M.D.
Professor of Medicine
Division of Infectious Diseases, Department of Medicine
Faculty of Medicine Ramathibodi Hospital, Mahidol University
What We Know and What We Need to Do
Global HIV Trends, 1990-2011
Change in incidence rate among adults 15-49 years old
Rank Opportunistic Infection Number %
1 Tuberculosis 79559 29.61
2 PCP 57235 21.3
3 Cryptococcosis 43339 16.14
4 Invasive candidiasis 14202 5.29
Opportunistic Infections in Thailand
Total = 268,706 AIDS patients reported in 1984-2005 Source: MOPH
5 Recurrent pneumonia 10070 3.75
6 Cerebral toxoplasmosis 8006 2.98
7 Penicilliosis marneffei 6709 2.5
8 AIDS dementia complex 4155 1.55
9 MAC 2597 0.97
10 Chronic herpes simplex infection 2448 0.91
25
30
35
40
45
Percentage
Causes of Death among AIDS in Thailand
0
5
10
15
20
25
TB PCP Crypto CMV MAC Toxo PML
AIDS patients reported in 1984-2005 Source: MOPH
Research Centre for Health Economics and Evaluation (ReCHEE)
Tuberculosis
Toxoplasmosis
Survival of AIDS Patients by First Presenting Opportunistic
Infections in Ramathibodi Hospital, Thailand, 1990-1994
Cryptococcosis
PCP
Toxoplasmosis
Other OIs
Sathapatayavongs B, et al. J Infect Dis Antimicrob Agents 1999; 16:69-72.
The disability-adjusted life year (DALY) is a measure of overall disease burden, expressed as the number of years lost due to ill-
health, disability or early death.
DALY = YLL + YLD. YLL = Years of Life Lost‘. YLD = Years Lived with Disability.
Vir
al
loa
d
Immunological response
Clinical response• less illnesses
• improved weight
• better well being
Effect of Antiretroviral Therapy
Limit of detection
Time
CD
4
Virological response
• better well being
• back to work• better quality of life
Research Centre for Health Economics and Evaluation (ReCHEE)
0.6
0.8
1.0
Pro
po
rtio
n o
f pa
tie
nts
wit
ho
ut d
ea
th fr
om
cryp
toco
cco
sis
ART
no ART
received ART
no ART-censored
received ART-censored
Survival Functions
P < 0.001
Received ART
Not Received ART
Survival Rate of HIV-infected Patients
with Cryptococcosis in Thailand
0.0 10.0 20.0 30.0 40.0 50.0 60.0
Study time (months)
0.0
0.2
0.4
Pro
po
rtio
n o
f pa
tie
nts
wit
ho
ut d
ea
th fr
om
cryp
toco
cco
sis
Not Received ART
Jongwutiwes U, et al. Curr HIV Res 2007.
0.6
0.8
1.0
Pro
bab
ilit
y o
f su
rviv
al (f
ree) fr
om
rela
pse
ART
no ART
received ART
no ART-censored
received ART-censored
ART
Relapse Rate of Cryptococcosis among
HIV-infected Patients in Thailand
0.0 10.0 20.0 30.0 40.0 50.0 60.0
Study time (months)
0.0
0.2
0.4
Pro
bab
ilit
y o
f su
rviv
al (f
ree) fr
om
rela
pse
No ART
HR = 5.47, P = 0.003
Jongwutiwes U, et al. Curr HIV Res 2007.
Received ART
Survival of HIV-infected Patients
with CMV Retinitis in Thailand
S. Sungkanuparph, et al. J Infect 2008.
Not Received ART
Research Centre for Health Economics and Evaluation (ReCHEE)
Research Centre for Health Economics and Evaluation (ReCHEE)
Time Trends of CD4 Cell Count Levels at the Initiation
of ART among Asian HIV-infected Patients
• Data from two regional cohort
observational databases (TASER-M and
TAHOD) were analyzed for
• trends in median baseline CD4 counts
• proportion of late ART initiation (CD4
< 200 cells/mm3 or prior AIDS)
• by calendar year
• 2,410 HIV-infected ART-naïve patients
from 21 sites in 13 Asian countries
Kiertiburanakul S, et al. CROI 2013. Abstract Y-117.
from 21 sites in 13 Asian countries
• Overall median (IQR) CD4 cell count at
ART initiation was 135 (43-229)
cells/mm3
• Median CD4 cell counts at ART initiation was not increased overtime,
from 170 cells/mm3 before 2007 to 136 cells/mm3 after 2009 (p for trend
0.268).
• Proportion of patients with late ART initiation decreased from 75.8%
before 2007 to 69.8% after 2009 (p for trend <0.001)
Time Trends of CD4 Cell Count Levels at the Initiation
of ART among Asian HIV-infected Patients
China 176
Hong Kong 97
India 216
Japan 268
S. Korea 279
Taiwan 240
Vietnam 211
Kiertiburanakul S, et al. CROI 2013. Abstract Y-117.
Cambodia 172
Indonesia 80
Malaysia 134 Philippines 192
Singapore 157
Taiwan 240Thailand 112
Median CD4 cell counts (cells/mm3) at antiretroviral therapy initiation
(These data are for the sites and not country representatives)
Time Trends of CD4 Cell Count Levels at the Initiation
of ART among Asian HIV-infected Patients
Kiertiburanakul S, et al. CROI 2013. Abstract Y-117.
P for trend
CD4 cell counts >200 cells/mm3 0.890
CD4 cell counts <200 cells/mm3 <0.001
Overall 0.268
Median CD4 cell counts at ART
initiation by calendar year
Time Trends of CD4 Cell Count Levels at the Initiation
of ART among Asian HIV-infected Patients
Kiertiburanakul S, et al. CROI 2013. Abstract Y-117.
Percentage of patients with late antiretroviral therapy initiation by calendar year
Research Centre for Health Economics and Evaluation (ReCHEE)
Time Trends of CD4 Cell Count Levels at the Initiation
of ART among Asian HIV-infected Patients
Univariate
Odds ratio (95% CI)p-value
Multivariate
Odds ratio (95% CI)p-value
Year of ART initiation
<2007
2007
2008
2009
ref
0.99 (0.60-1.63)
0.86 (0.57-1.31)
0.61 (0.41-0.92)
0.965
0.490
0.018
ref
1.52 (0.74-3.10)
1.58 (0.86-2.90)
1.18 (0.65-2.16)
0.252
0.141
0.582
Factors associated with late antiretroviral therapy initiation
2009
>2009
0.61 (0.41-0.92)
0.33 (0.21-0.50)
0.018
<0.001
1.18 (0.65-2.16)
0.69 (0.37-1.30)
0.582
0.249
Gender
Female
Male
ref
1.40 (1.10-1.78) 0.006
ref
1.70 (1.24-2.33) 0.001
HIV exposure category
Heterosexual
Homosexual
IDU
Other
ref
0.64 (0.49-0.85)
1.98 (1.16-3.39)
0.80 (0.52-1.22)
0.002
0.012
0.297
ref
0.58 (0.40-0.84)
1.80 (0.94-3.43)
0.86 (0.47-1.59)
0.004
0.075
0.641
Kiertiburanakul S, et al. CROI 2013. Abstract Y-117.
- 466 patients, mean age 38.8 years, 58.6% were males.
- Risks of HIV-1 infection: heterosexual (77.7%), homosexual (16.7%), and IVDU (5.6%)
- Median (IQR) CD4 = 176 (42-317) cells/mm3
- Median (IQR) HIV-1 RNA = 68,600 (19,515-220,330) copies/mL
- HIV-1 subtypes = CRF01_AE (86.9%), B (8.6), others (4.5%)
- Prevalence of primary HIV-1 drug resistance = 4.9%
- NRTI = 1.9%, NNRTI = 2.8% , and PI = 1.7%
• HIV/AIDS has been one of the leading causes of death in Asia-
Pacific particularly in resource-limited countries
• Rapidly scaling up of combination ART has led to significant
reductions in morbidity and mortality in HIV-infected patients
• However, the majority of HIV-infected patients in this region start
ART with advanced disease
• Factors significantly associated with a higher risk of disease
progression were younger age, lower BMI, and lower CD4 count
Summary
progression were younger age, lower BMI, and lower CD4 count
• In Asia, CD4 count at ART initiation does not increase over time
• ART initiation at higher CD4 cell counts remains a challenge
• HIV drug resistance can decrease treatment success and must be
prevented
• Getting to zero new AIDS-related death, strategic interventions to
increase earlier diagnosis of HIV infection and rapid access to ART
must be implemented, especially among those in resource-limited
countries in this region
Research Centre for Health Economics and Evaluation (ReCHEE)
Research Centre for Health Economics and Evaluation (ReCHEE)
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