David Metzger, PhD
University of PennsylvaniaHIV Prevention Research Division
Department of Psychiatryand
Treatment Research Institute
Philadelphia, Pennsylvania
Addiction treatment as HIV prevention in Asia
Philadelphia
University of Pennsylvania
“From harm reduction to addiction treatment”
• HIV and injection drug use in Asia
• Evidence based responses to HIV among PWID
• Need for expanded treatment of biological and behavioral aspects of drug abuse
• Strategies for expanding treatment for substance use disorders
• NIH and China CDC collaboration: HPTN 058
截至 2013年携带 HIV的成人和儿童人数
Current global AIDS epidemiology
• Approximately 35,000,000 living with HIV/AIDS
• Over 3,000,000 IDUs living with HIV/AIDS
• Outside of sub-Saharan Africa, over 33% of all new infections are estimated to be attributable to injection drug use
• No estimates of the major role of alcohol and non-injection drug use
HIV in China: 780,000 people living with HIV
中国的 HIV 与毒品滥用情况HIV and drug abuse in China
• 780,000 living with HIV/AIDS—28% attributable to injection drug use (IDU)
• First recognized in Yunnan Province in 1989
• In 2003, 44% of all HIV infections were due to IDU
• 48,000 new infections in 2011--18% attributable to injection drug use
• No estimate of the number of infections related to non-injection drug use or alcohol use
UNAIDS, 2011
HIV prevalence among people who inject drugs, 2010-2013
Source: Prepared by www.aidsdatahub.org based on 1) Integrated Biological and Behavioural Surveys; 2) HIV Sentinel Surveillance Surveys; 3) www.aidsinfoonline.org
0
10
20
30
40
50
1.14.4
6.3 6.3 7.210.3
18.7 18.9
24.8 25.227.2
36.4
46.1
HIV
pre
va
len
ce
(%
)
* Kathmandu; ** Cebu and Mandaue
海洛因
Criminal justice responses to control drug use have not been effective
武汉的强制戒毒中心
Evidence –based HIV prevention strategies for drug using populations
• Education about HIV transmission
• HIV counseling and testing
• Increased access to sterile injection resources and condoms
• Methadone treatment
• HIV treatment
21%
13%
18%
51%
21%
39%
0%
10%
20%
30%
40%
50%
60%
B 6 12 18 24 30 36 42 48 60 72
Months
In Treatment Out of Treatment
Six year HIV infection rates by treatment status at time of enrollment
(Metzger et al. 1993)
Incidence of HBV and HCV 12 Months Following Treatment Entry
0%
2%
4%
6%
8%
10%
12%
HBV HCV
Left
Interupted
Remained
(Thiede,Hagan,and Murrill, 2000)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Any use Injection
No Tx (N=360)
Past Tx (N=74)
Current Tx (N=123)
Drug use and injection among 557 heroin users by methadone treatment status, Sichuan Province, China
(Han-Zhu Qian et al, 2008)
0%
2%
4%
6%
8%
10%
12%
14%
16%
Sharing
No Tx (N=360)
Past Tx (N=74)
Current Tx (N=123)
(Han-Zhu Qian et al, 2008)
Needle sharing among 557 heroin users by methadone treatment status, Sichuan Province, China
Proof of concept: 0ver 25 years of evidence that MMT is effective HIV prevention
Early ARV reduced transmission by 94%
Early Therapy Delayed Therapy
0
5
10
15
20
25
30
Linked infections
Linked infections
Methadone treatment increases access and adherence to HIV treatment, and likelihood of viral supression
中国的美沙酮治疗项目2003年 12月,分布在 5个省份的 8个诊所被批准成为中国的第一波社区美沙酮治疗中心。
西藏
青海
甘肃 内蒙古
黑龙江
吉林
辽宁
贵州
广西 广东
湖南江西
福建
台湾
浙江
江苏
上海
山东
陕西
山西宁夏
新疆
四川 湖北
河南
安徽
云南
河北
北京
天津
香港澳门
2011 年美沙酮的治疗情况
青海2 甘肃
17
吉林2
贵州54
GuangxiMMT=53
广东41
湖南47
江西12
福建8
浙江18
江苏11
陕西18
宁夏3
XinjiangMMT=27
四川32
湖北32
安徽
云南67
北京8
海南19
重庆26
上海87
770 个美沙酮诊所十六万六千海洛因使用者
河南1
N=7702n=3041
N=12001n=5810
MMT:美沙酮诊所N:累积海洛因使用者n:当前海洛因使用者
New HIV Infections by risk group in China
Mathers et al., the Lancet , 2010
Clear need for more treatment options
Reported number of people who receiving opioid substitution therapy, 2012-2013
China
Mal
aysi
a
Viet N
amIn
dia
Indones
ia
Mya
nmar
Thaila
nd
Nepal
Bangla
desh
Cambodia
Mal
dives
Afghan
ista
n0
50,000
100,000
150,000
200,000
250,000
201,730
65,249
15,542 15,0005,329 4,397 4,068 494 411 252 109 71
2012
2013
Nu
mb
er
of
pe
op
le o
n O
ST
Source: Prepared by www.aidsdatahub.org based on Global AIDS Response Progress Report 2014 – Online Country Reports
Challenge: expand addiction treatment access
• Increase range of treatment options
• Integrate MAT into HIV and primary health care settings
• Improve the effectiveness of existing treatments
Biological components
生物学阐释 ( 依赖性 )
Impact and changes in central nervous system
Genetic (family history, response to addiction medications)
Behavioral components
行为学阐释(成瘾)Change behavioral patterns
Interrupt learned associations and avoid “triggers” for craving
Effective treatment requires attention to both biology and behavior--medication and counseling– Medication 对成瘾的有效控制需要同时关注两点:用药和咨询
Addiction is a chronic medical condition成瘾是一种慢性的(需要)医学(治疗)的病症
NIH (NIDA) 和中国 CDC 的合作Buprenorphine/Naloxone Treatment: HPTN 058 (2007-2012)
HPTN 058 tested buprenorphine/naloxone (Suboxone) and Behavioral Drug and Risk Counseling as HIV prevention
HPTN 058 检验丁丙诺菲( Buprenorphine ) / 纳洛酮( Naloxone ) (Suboxone) 的药效、行为治疗以及风险咨询的效果
First use of Buprenorphine-Naloxone in China and Thailand
Primary outcome: Prevention of HIV infection主要结果:预防 HIV 感染
Conducted in Chiang Mai, Thailand; Guangxi and Xinjiang, China这一研究在泰国清迈,中国的广西和新疆进行
丁丙诺啡( Buprenorphine ) / 纳洛酮( Naloxone ) (Suboxone)
Partial opiate agonist with longer half-life阿片受体部分激动剂,有更长的半衰期
Three times per week dosing is possible每周摄入三次的频率成为可能
Reduced risk of overdose降低了用药过量的风险
Less severe withdrawal降低了突然停止用药后产生的副作用
Fewer interactions with anti-retrovirals减少与抗逆转录病毒( anti-retrovirals )的相互作用
N=201N=161
N=411
N=477
1250 opiate dependent injectors were recruited from four communities in Thailand and China
HPTN 058: comparing new delivery strategies using buprenorphine/naloxone
Opiate injectorsrecruited from
communityand screened
Short-Term Medication Assisted Treatment
Suboxone detox At Bx and 6 months
plus one year counseling;Referral to
local resources
Long-Term Medication Assisted Treatment
12 months of Suboxone 3x per week and one year
counseling;Referral to
local resources
HIV testing and counseling
Every 6 months Year 02
HIV testing and counseling
Every 6 months Year 02
If not eligible, referred to local resources
行为治疗药物和风险咨询( BDRC )
Type of cognitive behavioral therapy认知行为治疗( cognitive behavioral therapy )
Focus on short term behavioral goals重点在于实现短期的行为目标
Uses behavioral contracts –”homework” 运用行为契约(治疗者和患者就短期行为目标达成的治疗契约)
Emphasis on drug use and risk behavior – breaking behavioral patterns and avoiding triggers主要用于治疗毒品滥用和其他相关问题
Relapse is view as a symptom, not a failure复吸的出现是可接受的
12 weekly sessions followed by 9 monthly sessions12 周的治疗周期,之后再进行 9 个月的周期治疗
Weekly Sessions
Monthly Sessions
Retained in Bup/Nal
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
LT-MATST-MAT
Proportion completing BDRC counseling sessions and Bup-Nal administration by study arm
Baseline week 26* week 52* week 78 week 1040
10
20
30
40
50
60
70
80
90
100
LT-MAT
ST-MAT
Percent injecting during prior 6 months by study arm
鸦片制剂尿检阳性结果
Baseline week 26 week 52 week 78 week 1040
5
10
15
20
25
30 Injected after someone else in prior 6 months
LT-MAT ST-MAT
75% reduction in needle sharing
(在最初的六个月中)使用他人使用过的注射器或针头注射毒品的患者比率
HIV infection rate has declined dramatically: HPTN 033 and HPTN 058
2003 20110
1
2
3
4
5
6
7
8
9
10
GuangxiXinjiang
JAIDS, 2015
Efficacy of behavioral drug and risk counseling (BDRC) in 5 MMT clinics in Jakarta (NIDA)
• Randomly assign 276 MMT patients to BDRC or TAU to improve:
Retention in MMTAccess to and retention in ARV
• MMT and ARV are embedded within primary health care clinics – Puskesmus
BDRC (141) TAU (135) Total
Male (%): 92% 86% 90%
Age: 31 31 31
Tx months: 21.9 21.4 21.6
HIV positive: 69% 64% 67%
Sample characteristics (N=276)
Baseline 6 Months 12months50
55
60
65
70
75
80
85
90
95
100
TAUBDRC
BDRC among MMT patients in Jakarta: Retention in MMT
Baseline 6 Months 12months0
10
20
30
40
50
60
70
TAUBDRC
BDRC among MMT patients in Jakarta: Retention in HIV Care
BDRC: factors associated with session attendance
Mean sessions attended = 9/18 (50%)
Baseline Factor OR
Take home doses 2.8Positive QOL 1.4Poly-drug use 0.15
Implementation of an Integrated Treatment for Opioid Addiction in Go Vap, Ho Chi Minh City (NIDA)
PAC Ho Chi Minh City
• Co-location of methadone and buprenorphine-naloxone within an HIV treatment setting
• Assessing acceptability and barriers
• Mixed methods observational design
• First use of Bup-Nal in Vietnam
Male (%): 96.6%
Age: 32.2 (SD=5.5)
HIV positive: 36.9%
New HIV Diagnosis: 7.3%
Sample characteristics (N=235)
Rapid enrollment in MMT
From 12/01/2013 to 09/30/2014 145 patients enrolled
– 92% of new patients started methadone at Go Vap clinic
45
MMT Retention rate
ANRS_Haiphong_15 Nov 2014 46
Retention rate = 96.6%
Retention rate = 86.3%
中国注册在案的毒品使用者 1991-2010 (x1,000)
Increasing variety of illicit drug use in China:It not just opiates
结论
Drug use is a global problem with similar and significant health and economic impact, on individuals, families, and communities
The most effective responses view drug abuse as medical condition with behavioral and biological components
Need to expand access to effective treatments for substance use disorders
Develop more delivery mechanism for behavioral interventions
Liying Ma, MD, PhDChinese AIDS Prevention and Control
China CDC
Yuyuan Liu, MSWUniversity of Pennsylvania
School of Social Policy and Practice
Peng Wang, MDDirector, Division of Substance Abuse Mental Health Center of Wuhan City
Hubei Province, China
Acknowledgements
PI: Charles O'Brien, MD, PhD - University of Pennsylvania, PA, USA Co-PI: Le Truong Giang, MD, PhD - HCMC AIDS Committee Co-PI: Jean-Pierre Daulouède, MD, Bizia/ESTHER Investigators
David Metzger, PhD, University of Pennsylvania, PA, USA
Gilles Raguin, MD, ESTHER
Lisa Huang, MD, ESTHER
Vincent Trias, ESTHER ESTHER Research staff in HCMC ESTHER Staff in Vietnam ESTHER Staff in Paris, France Go Vap Center Staff in Ho Chi Minh City PAC Ho Chi Minh City Ministry of Health of Vietnam, Hanoi VAAC, Hanoi
Complacency缺少关注
High Risk Behavior高危行为
HumanRightsAbuses
对人之权利的侵犯
Stigma-Tization
污名
Access To
Care获得治疗的
途径短缺
Sexism性别歧视
Ignorance被轻视Poverty
贫困
Discrimin-Ation歧视
Disem-poweredWomen
作为弱势群体的妇女
Prejudice偏见
Denial否定
鸣谢 Jim Hoxie