nora d. volkow, m.d. director. injecting drug use is also an increasing concern in east and...
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Drugs and HIV:Challenges and Strategies
Nora D. Volkow, M.D.Director
Injecting drug use is also an increasing concern in East andSouth-East Asia, with an estimated 3.9 million (range:3,043,500-4,913,000) drug users injecting mostly opioidsand, to a lesser extent, methamphetamine, while an estimated661,000 (range: 313,333-1,251,500) injecting drugusers are living with HIV, according to the ReferenceGroup to the United Nations on HIV and Injecting DrugUse.
Source: UNAIDS 2012 Global Report
HIV prevalence among sex workers HIV prevalence among MSM HIV prevalence among IDU HIV prevalence (15-49) in the general population
HIV Prevalence in Adults and Key Populations
HIV Seroconversion at 18 MonthsBy Receipt of Treatment
00
55
1010
1515
2020
2525
Rat
e of
Ser
ocon
vers
ion
(%
)
Treatment Status
No treatmentNo treatment
Partial treatmentPartial treatment
Continuous treatmentContinuous treatment
Metzger, et al. (1993). Acquired Immune Deficiency Syndromes, 6, 1049-1056.
Medications for Substance Use Disorders Are Effective in PREVENTING HIV
IDUs Receiving Methadone or BuprenorphineTx, 2009
Wolfe D et al., Lancet 2010; 376: 35-366.
Global Challenges For Treatment of IDU
Full and Partial Agonists vs Antagonists Treatment Strategies for Opioid Addiction
effect
no effect
agonist antagonist
an agonist drug has anactive site of similar shapeto the endogenous ligandso binds to the receptor
and produces the same effect
an antagonist drug is closeenough 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 bindingO
pio
id E
ffec
t
Full Agonist(Methadone)
Partial Agonist(Buprenorphine)
Antagonist(Naloxone)
Log Dose
Normal Control
Methadone Maintained Patient
Source: Kling et al., JPET, 2000.
Specific Binding [18F]cyclofoxy (m
ligand)
30-35 % receptor occupancy for methadone doses > 80 mg a day
Specific Binding [11C]carfentail (m
ligand)
27-47 % occupancy for 2mg Bup85-92% occupancy for 16 mg Bup94-98% occupancy for 32 mg Bup
Greenwald, MK et al., Neuropsychoph, 2003.
Krupitzky et al., Lancet 2011; 377: 1506-1513.
Placebo: N=124XR-NTX: N=126
IM Injectionevery 4 weeksfor 24 weeks
XR=NTX: Positive Phase 3 ResultsOpioid Dependence
Primary EndpointRates of opioid-free urine tests p=0.0002
Secondary Endpoints: XR-NTX vs. PlaceboImproved study retention during 6 mo study period p=0.004Lower opioid craving scores p<0.001Less incidence of relapse to physiologic opioid dependence p=0.017Less self-reported opioid use p=0.003
Median Percent Opioid-Negative UrinesP
erce
nt
of W
eek
ly U
rin
e T
ests
100%
80%
60%
40%
20%
0%PLACEBO XR-NTX
Few could have imagined that we’d be talking about the real possibility of an AIDS-free generation President Obama, December 1,
2011
HPTN 052: HIV Treatment as Prevention
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)
GD Kirk, N Galai1, J Astemborski, B Linas, D Celentano, SH Mehta, D VlahovMontaner et al., Lancet 2008
Poster presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI), Boston MA, February 27-March 3, 2011
HIV-In
fected
HIV-D
iagn
osed
Linked
to C
are
Retain
ed in
Car
e
Need A
RT
On ART
Adheren
t/Undete
ctable
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,10
6,40
0
874,
056
655,
542
437,
028
349,
622
262,
217
209,
773
1,17
8,35
0
941,
950
725,
302
480,
395
426,
590
328,
475
Gardner, et al. CID 2011.Cohen, et al. MMWR 2011
100%
80%
62%
40%
32%36%
28%
79%
59%
41%
24% 19%
Major Gaps in the Implementation Cascade
We have the tools: SEEK, TEST TREAT AND RETAINBut 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
Westergaard RP et al., J Int AIDS Soc 2012; 15:10.
Physicians are reluctant to treat IDU with ART owing to alleged poor compliance.
IDUs as Share of Total HIV Cases & of Patients Receiving ART, 2008
Wolfe D et al., Lancet 2010; 376: 35-366.
Global Challenges For Treatment of IDU
Gil et al
90
80
70
60
Inci
denc
e/yr
Vira
l loa
d <
50/
mL
(%)
Acquired resistancefalling
Plasma viral load suppression rising
Improved Virological Outcomes in BC Concomitant with Decreasing Incidence of HIV Drug Resistance
Gill et al., CID 2010:50 HIV/AIDS
All-Cause Mortality
Wilcoxon test P = .47
Cu
mu
lati
ve I
nci
den
ce o
f M
orta
lity
, %
IDUNon-IDU
Non-IDU 2201 1984 1658 1383 1148 928 785 634IDU 915 862 752 653 546 468 392 339
No. at risk
35
30
25
20
15
10
5
00 12 24 36 48 60 72 84
Months
Mortality Rate Among 3116 Antiretroviral-Naive Patients
Initiating HAART
Wood, E. et al. JAMA 2008;300:550-554.
The incidence rate of resistance between 1997-2008 decreased >12-fold (exponential rate), concomitant with a linear increase in the suppression of viral load.
Major ChallengesSEEK, TEST TREAT AND RETAIN
1. Treating Substance Abusers with ART
2.Treating HIV+ Patients for Substance Abuse RETAIN requires treatment of SUD
Uhlmann S et al., Addiction 2010; 105(5):907-913.
Methadone Maintenance Therapy Promotes Initiation Of
Antiretroviral Therapy IDU
Antiretroviral Adherence and HIV Treatment Outcomes Among HIV/HCV
Co-Infected IDU: Role of Methadone
Adj
ust
ed O
dds
Rat
io
Palepu A et al., Drug and Alcohol Dependence 2006; 84: 188-194.
Methadone Maintenance Therapy Improves HIV Outcomes in IDU
Uhlmann S et al., Addiction 2010; 105(5):907-913.
13,688 SA treatment facilities only 1,132 (8%) prescribe OST
Less <12% of opioid dependent patients received OST
2010 NSDUH, National Findings, SAMHSA, OAS, 2011.
Self Help Group
Outpatient Rehab
Inpatient Rehab
Outpatient Mental Health Center
Hospital Inpatient
Doctor’s Office
Emergency Room
Prison or Jail
Numbers in Millions0 .5 1.0 1.5 2.0 2.5
2.32.3
1.71.7
1.01.0
1.01.0
0.50.5
Location TX Received
0.70.7
0.70.7
0.30.3
In a given year about 14% of allpeople in the US with HIV pass through a correctional facility
Of those incarcerated (total 2.3M); 70-80% need SUD treatment. In 2010 only 1600 opioid dependent on OST
Of 22.1M Americans 12 or Older Who Are Dependent On Drugs or Alcohol
Only 19% Received Treatment for SU
Minimal integration between HIV and SUD care in health care setting
C = Counseling Only C+T = Counseling & Treatment Referral C+M = Counseling & Methadone Started in Prison
11
85
35
57
64
46
80%
C C + T C + M
Days In Treatment Days Used Heroin
Source: Gordon, MS et al., Addiction 103:1333-1342, 2008.
Treatment Linkage & Days Used Heroin 6 Months Post-release
70%60%50%40%30%20%10%0%
90%
Injec
tion S
tatu
s
Complet
ed 6
mo. F
ollow-U
p
Urine +
for O
pioid
s at 6
mo.
Any Inca
rcer
ation in
Past
6 mo.
Emplo
yed a
t 6 m
o. Follo
w-Up
0
20
40
60
80
100
120
46
96
4
15
5654
3944
50
39
CompletersNoncompleters
(Received all monthly injections)(Did not receive all monthly injections)
Per
cen
t
Treatment Completion and 6 Mo. Outcomes
Coviello DV et al., Substance Abuse 2012; 33:48-59.
Multisite Pilot Study of XR-NTX for Previously Opioid-Dependent Parolees and Probationers
Marshall BDL et al., PLoS ONE 2012; 7(9): e44833.
Risk Network Structure at Model Initialization of a Representative Subsample of 1000 Agents,
Stratified by Drug Use Status
IDUs—Red, NIDUs—Blue, NUs--Green
Gwadz – New York UniversityCunningham – Albert EinsteinEl-Sadr -- Columbia
Metsch – University of Miami
Khan -- UCSF
Ann Duerr – Fred Hutchinson Cancer RC`
Lucas – `Johns Hopkins
Wechsberg – Research Triangle Institute
Kurth – New York University
Samet – Boston Medical Center
```
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 IMPLEMENTATIONSubstance abuse treatment programs Health Care (i.e., STD clinics)Criminal Justice SystemCountries where IDU is
driver of HIV epidemic
Recent International HIV AwardsNIDA 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
• 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)
International Funded Grants
Recent International AwardsNIDA Fellowship Awardees
25
• 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)
International Program FellowsIAS NIDA Fellows
HIV/AIDS in America
Carlos Del Rio
Grant Colfax
Josiah Rich
Don DesJarlais
Moupali Das
Steven Shoptaw
``Steffanie Strathdee &
Thomas Patterson