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

0

5

10

15

20

25

Rat

e of

Ser

ocon

vers

ion

(%)

Treatment Status

No treatmentPartial 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

effectno 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

pioi

d 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 UrinesPe

rcen

t of W

eekl

y U

rine

Tes

ts100%

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

iagnose

d

Linked to

Car

e

Retained

in C

are

Need A

RT

On ART

Adherent/U

ndetecta

ble0

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

Cum

ulat

ive

Inci

denc

e of

Mor

talit

y, %

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

uste

d 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

2.3

1.7

1.0

1.0

0.5

Location TX Received

0.7

0.7

0.3

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

5764

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 Status

Completed

6 mo. F

ollow-U

p

Urine +

for O

pioids at 6

mo.

Any Inca

rcera

tion in

Past 6 m

o.

Employed at 6

mo. F

ollow-U

p0

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)

Perc

ent

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 StatusIDUs—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