David Metzger, PhD University of Pennsylvania HIV Prevention Research Division Department of Psychiatry and Treatment Research Institute Philadelphia,

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