Download Nora D. Volkow, M.D. - USA (D101.1)

Drugs and HIV:
Challenges and Strategies
Nora D. Volkow, M.D.
Director
HIV Prevalence in Adults and Key Populations
Injecting drug use is also an increasing concern in East and
South-East Asia, with an estimated 3.9 million (range:
3,043,500-4,913,000) drug users injecting mostly opioids
and, to a lesser extent, methamphetamine, while an estimated
661,000 (range: 313,333-1,251,500) injecting drug
users are living with HIV, according to the Reference
Group to the United Nations on HIV and Injecting Drug
Use.
HIV prevalence among sex workers
HIV prevalence among MSM
HIV prevalence among IDU
HIV prevalence (15-49)
in the general population
Source: UNAIDS 2012 Global Report
Rate of Seroconversion (%)
Medications for Substance Use Disorders Are
Effective in PREVENTING HIV
HIV Seroconversion at 18 Months
By Receipt of Treatment
25
No treatment
Partial treatment
Continuous treatment
20
15
10
5
0
Treatment Status
Metzger, et al. (1993). Acquired Immune Deficiency Syndromes, 6, 1049-1056.
Global Challenges For Treatment of IDU
IDUs Receiving
Methadone or BuprenorphineTx, 2009
Wolfe D et al., Lancet 2010; 376: 35-366.
Full and Partial Agonists vs Antagonists
Treatment Strategies for Opioid Addiction
agonist
antagonist
no effect
effect
an agonist drug has an
active site of similar shape
to the endogenous ligand
so binds to the receptor
and produces the same effect
an antagonist drug is close
enough in shape to bind to the
receptor but not close enough
to produce an effect. It also
takes up receptor space and so
prevents the endogenous
ligand from binding
Opioid Effect
Full Agonist
(Methadone)
Partial Agonist
(Buprenorphine)
Antagonist
(Naloxone)
Log Dose
Specific Binding
Specific Binding
11C]carfentail (m ligand)
18
[
[ F]cyclofoxy (m ligand)
Normal Control
Methadone Maintained Patient
30-35 % receptor occupancy for
methadone doses > 80 mg a day
Source: Kling et al., JPET, 2000.
27-47 % occupancy for 2mg Bup
85-92% occupancy for 16 mg Bup
94-98% occupancy for 32 mg Bup
Greenwald, MK et al., Neuropsychoph, 2003.
XR=NTX: Positive Phase 3 Results
Opioid Dependence
Primary Endpoint
Rates of opioid-free urine tests
p=0.0002
Percent of Weekly Urine Tests
Median Percent Opioid-Negative Urines
100%
80%
Placebo: N=124
XR-NTX: N=126
60%
40%
IM Injection
every 4 weeks
for 24 weeks
20%
0%
PLACEBO
XR-NTX
Secondary Endpoints: XR-NTX vs. Placebo
Improved study retention during 6 mo study period
Lower opioid craving scores
Less incidence of relapse to physiologic opioid dependence
Less self-reported opioid use
Krupitzky et al., Lancet 2011; 377: 1506-1513.
p=0.004
p<0.001
p=0.017
p=0.003
HPTN 052:
HIV Treatment as
Prevention
Few could have imagined that we’d be
talking about the real possibility of an
AIDS-free generation
President Obama, December 1, 2011
How does HIV Treatment as
Prevention pertain to Drug Abusers?
Total cumulative cases of AIDS attributable
to IDU since the beginning of the epidemic
is 32.6%
HAART as HIV Prevention
Decline in Community Viral Load is Strongly Associated
With Declining HIV Incidence among IDUs (ALIVE)
Montaner et al., Lancet 2008
GD Kirk, N Galai1, J Astemborski, B Linas, D Celentano, SH Mehta, D Vlahov
Poster presented at the 18th Conference on Retroviruses and Opportunistic
Infections (CROI), Boston MA, February 27-March 3, 2011
Major Gaps in the Implementation Cascade
1,400,000
100%
80%
19% 28%
328,475
24%
426,590
32%
36%
209,773
40% 41%
262,217
941,950
62%
349,622
0
655,542
200,000
59%
874,056
400,000
1,178,350
600,000
1,106,400
800,000
480,395
79%
437,028
1,000,000
Gardner, et al. CID 2011.
Cohen, et al. MMWR 2011
725,302
1,200,000
We have the tools: SEEK, TEST TREAT AND RETAIN
But we also have MAJOR CHALLENGES
1. Treating Substance Abusers with HAART
2. Treating HIV+ Patients for Substance Abuse
IDU HIV+ Are Much Less Likely to Receive HAART
Percentage Of Providers Who Would Defer ART By CD4+ Count
and Injection Drug Use Status
Physicians are
reluctant to
treat IDU with
ART owing to
alleged poor
compliance.
Westergaard RP et al., J Int AIDS Soc 2012; 15:10.
Global Challenges For Treatment of IDU
IDUs as Share of Total HIV Cases &
of Patients Receiving ART, 2008
Wolfe D et al., Lancet 2010; 376: 35-366.
Incidence/yr
Gill et al., CID 2010:50 HIV/AIDS
Acquired resistance
falling
Viral load
< 50/mL (%)
Gil et al
90
80
70
Plasma viral load
suppression rising
60
The incidence rate of resistance between
1997-2008 decreased >12-fold (exponential
rate), concomitant with a linear increase
in the suppression of viral load.
Mortality Rate Among 3116
Antiretroviral-Naive Patients
Initiating HAART
Cumulative Incidence of Mortality, %
Improved Virological Outcomes in
BC Concomitant with Decreasing
Incidence of HIV Drug Resistance
All-Cause Mortality
35
IDU
Non-IDU
30
25
20
15
10
5
Wilcoxon test P = .47
0
0
12
24
No. at risk
Non-IDU
IDU
36
48
60
72
84
Months
2201
915
1984
862
1658
752
1383
653
1148 928 785 634
546 468 392 339
Wood, E. et al. JAMA 2008;300:550-554.
Major Challenges
SEEK, TEST TREAT AND RETAIN
1. Treating Substance Abusers with ART
2. Treating HIV+ Patients for Substance Abuse
RETAIN requires treatment of SUD
Methadone Maintenance Therapy Improves
HIV Outcomes in IDU
Uhlmann S et al., Addiction 2010; 105(5):907-913.
Uhlmann S et al., Addiction 2010; 105(5):907-913.
Antiretroviral Adherence and HIV
Treatment Outcomes Among HIV/HCV
Co-Infected IDU: Role of Methadone
Adjusted Odds Ratio
Methadone Maintenance Therapy
Promotes Initiation Of
Antiretroviral Therapy IDU
Palepu A et al., Drug and Alcohol Dependence 2006; 84: 188-194.
Of 22.1M Americans 12 or Older Who Are
Dependent On Drugs or Alcohol
Only 19% Received Treatment for SU
13,688 SA treatment facilities only
1,132 (8%) prescribe OST
Less <12% of opioid dependent
patients received OST
Minimal integration between
HIV and SUD care in health
care setting
In a given year about 14% of all
people in the US with HIV pass
through a correctional facility
Location TX Received
2.3
Self Help Group
Outpatient Rehab
1.7
Inpatient Rehab
1.0
Outpatient Mental
Health Center
1.0
0.7
Hospital Inpatient
0.7
Doctor’s Office
0.5
Emergency Room
Prison or Jail
0.3
0
Of those incarcerated (total 2.3M);
70-80% need SUD treatment. In 2010
only 1600 opioid dependent on OST
.5
1.0
1.5
2.0
2.5
Numbers in Millions
2010 NSDUH, National Findings, SAMHSA, OAS, 2011.
Treatment Linkage & Days Used Heroin
6 Months Post-release
Days In Treatment
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Days Used Heroin
85
64
57
46
35
11
C
C+ T
C=
Counseling Only
C+T = Counseling & Treatment Referral
C+M = Counseling & Methadone Started in Prison
Source: Gordon, MS et al., Addiction 103:1333-1342, 2008.
C+ M
Multisite Pilot Study of XR-NTX for Previously
Opioid-Dependent Parolees and Probationers
Treatment Completion and 6 Mo. Outcomes
120
Percent
Completers (Received all monthly injections)
Noncompleters (Did not receive all monthly injections)
96
100
80
60
56
54
50
46
40
44
39
20
39
15
4
0
Injection Status Completed 6 mo.
Urine + for
Any Incarceration Employed at 6
Follow-Up
Opioids at 6 mo.
in Past 6 mo.
mo. Follow-Up
Coviello DV et al., Substance Abuse 2012; 33:48-59.
Risk Network Structure at Model Initialization of a
Representative Subsample of 1000 Agents,
Stratified by Drug Use Status
IDUs—Red, NIDUs—Blue, NUs--Green
Marshall BDL et al., PLoS ONE 2012; 7(9): e44833.
What is NIDA doing?
1. NEW THERAPEUTICS for IDU
Long lasting medications to improve compliance
Medications not based on opioid substitution
Vaccines and other immunotherapies
2. STTR IMPLEMENTATION
Substance abuse treatment programs
Health Care (i.e., STD clinics)
Criminal Justice System
Countries where IDU is
driver of HIV epidemic
Khan -- UCSF
Samet – Boston Medical Center
Gwadz – New York University
Cunningham – Albert Einstein
El-Sadr -- Columbia
Metsch – University of Miami
Lucas – `Johns Hopkins
Kurth – New York University
Ann Duerr – Fred Hutchinson Cancer RC`
Wechsberg – Research Triangle Institute
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Recent International HIV Awards
NIDA Funded Grants
• ARGENTINA
• AUSTRALIA (2)
• BOTSWANA (2)
• BULGARIA
• CAMBODIA (2)
• CANADA (11)
• CHILE
• CHINA (13)
• CZECH REPUBLIC
• EL SALVADOR
• ESTONIA
• ETHIOPIA
• GEORGIA (4)
• GREECE
• HUNGARY
• INDIA (9)
• INDONESIA (2)
• KAZAKHSTAN (3)
• KENYA (2)
• MALAWI
International Funded Grants
• MALAYSIA (2)
• MEXICO (19)
• MOZAMBIQUE
• MYANMAR
• NETHERLANDS
• NICARAGUA
• PAKISTAN
• PERU (2)
• POLAND
• ROMANIA
• RUSSIA (6)
• RWANDA
• SENEGAL
• SOUTH AFRICA (12)
• TANZANIA U REP (2)
• THAILAND (2)
• UKRAINE (6)
• UNITED KINGDOM
• VIETNAM (7)
• ZAMBIA (2)
Recent International Awards
NIDA Fellowship Awardees
International Program Fellows
IAS NIDA Fellows
• Abagiu, Adrian- Romania (2011)
• Ahmed, Munir- Bangladesh (2009)
• Boci, Arian- Albania (2008)
• Chtenguelov, Victor- India (2005)
• Desai, Nimesh G.- India (2008)
• Dvoriak, Sergii- Ukraine (2006)
• Isralowitz, Richard- Israel (2005)
• Kader, Rehana- South Africa (2008)
• Kasirye, R.- Uganda (2003)
• Khin, Thanda- Burma (2010)
• Malta, Monica- Brazil (2005)
• Nurhidayat, Adhi- Indonesia (2008)
• Otiashvili, David- Georgia (2011)
• Piralishvili, Gvantsa- Georgia (2009)
• Poudyal Chhetri, Meen- Nepal (2008)
• Simoes, Anna- Brazil (2005)
• Telles–Dias, Paulo Roberto- Brazil (2011)
• Toussova, Olga- Russia (2007)
• Tsarouk, Tatiana- Russia (2006)
• Vasilev, Georgi- Bulgaria (2010)
• Zhao, Min- China (2005)
• Zubaran, Carlos- Australia (2010)
25
Josiah Rich
Moupali Das
Don DesJarlais
HIV/AIDS in America
Steven Shoptaw
Grant Colfax
Steffanie Strathdee &
Thomas Patterson
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Carlos Del Rio