Download Human Immunodeficiency Virus (HIV) Acquired Immunodeficiency

Recreational Drugs,
HIV, and
Antiretroviral Therapy
Modified by:
Patrick Clay, PharmD
UNT System College of Pharmacy
[email protected]
O: (817) 735-2798
Originally designed and developed by:
Frank Romanelli, Pharm.D., MPH, BCPS
Professor of Pharmacy, Medicine, & Health Sciences
Associate Dean for Education, University of Kentucky
Objectives
Define the term “club drugs.”
 List potential clinical and toxic effects of
club and recreational drugs.
 Describe potential effects of recreational
drug use upon ARV therapy.
 Discuss HIV specific adverse consequences
of recreational drug use.

ICE
m&m
“CLUB DRUGS”
‘Recreational Drugs’
*SOCIAL LUBRICANTS*
Substances used in a
recreational fashion to
enhance social experiences.
Club Drugs
Not all recreational drugs are
considered ‘Club Drugs’
 Produce dis-inhibition
 Common substances of abuse at bars,
circuit parties, raves

Rave


All night parties
involving loud
music, laser light
shows, and
marathon dancing.
Most commonly
held in large open
areas such as old
warehouses.
Circuit Party


Most commonly three
day weekend events
centered in large urban
areas.
Attendees pay one
lump sum to attend
multiple events
throughout the
weekend culminating in
one final large party.
Club Drugs





Methylenedioxymethamphetamine
(MDMA) “Ecstasy”
Gammahydroxybutyric Acid
(GHB) “G”
Ketamine
“Special K”
Amyl and Butyl Nitrites
“Poppers”
Methamphetamine
“Crystal” “Tina”
Methylenedioxymethamphetamine
Amphetamine derivative which leads to
exaggerated levels of neurotransmitters
throughout the CNS.
• Ecstasy, E, XTC
• M and M
• Hug Drug
Epidemiology




Within the US, National Drug Intelligence
Center now equates MDMA use to that of
heroin and cocaine.
MDMA estimated to be one of the fastest
growing drug of abuse in the US.
2000: 1.4 million HS seniors used MDMA.
2005: 2.5% of HS seniors reported ‘ever-use.’
Availability
Amsterdam – “Ecstasy Capitol of the
World”
 Commonly manufactured in clandestine
laboratories
 High level of impurities and contaminants
(DM, ASA, Pseudoephedrine)

What does “Hug Drug” look
like?
Audience Participation time!
A.
B.
C.
White tablet
Pink capsule
Never scored
History of Abuse
Created in 1914 for appetite control
 Used in 1970s as a means of enhancing
behavior therapy
 Entered club scene in 1980s
 Classified as a C-I
 2001, FDA approval of trial involving
post-traumatic stress disorder

Street Sales
Sold in tablet form
 Typical tablet contains 50-150mg of
active ingredient
 Cost: $20-40.00 per tablet

Pharmacology
Structurally related to the stimulant
methamphetamine and hallucinogen
mescaline
 Increases levels of all NTs within CNS
synapses
 Inhibition of MAO

Clinical Effects
Increased energy
 Talkative, open-minded
 Intimacy
 Distorted senses
 Decreased fear, aggression,
defensiveness
 Hallucinations
 Teeth grinding

Club Drug Paraphernalia
Gamma-hydroxybutyrate
Naturally occurring fatty acid derivative
of CNS neurotransmitter GABA
Liquid E
 Gib, GBH, Grievous Bodily Harm,
Georgia Home Boy, “G”
 Soap, Scoop, Salty Water
 Easy Lay

Availability
Controlled substance C-I
 Internet recipes available
 Gammabutyrolactone (GBL)
 1,4-butanediol (1,4-BD)

History of Abuse
Early 1990s - Dietary supplement
purported to increase muscle mass,
increase libido, metabolize fat
 Mid-1990’s - Popularity increased,
euphoric effects recognized
 Late 1990’s – Established club and date
rape drug, FDA ban on OTC sales

History of Abuse
2000 – C-I status in US
 Early 2000 - GBL and 1,4-BD become
popular precursor sources of GHB
 FDA issues warning letters re: GBL and
1,4-BD
 Commonly imported from Europe
 Manufactured from internet recipes and
clandestine labs

Street Sales
Oral dosage form
 Typical dose “one
capful”
 Often admixed into
water bottles
 $5.00-$10.00/dose

Pharmacology





Normally 1/1000th the concentrations of
GABA within CNS
GHB endogenous CNS chemical
Mediates: sleep cycles, temperature, memory
Gets in your head easily (lipophilic, crosses
BBB rapidly)
Impacts levels of growth hormone
Clinical Effects
Dose-related CNS depression
 Amplification with ethanol or other
CNS depressants
 Often ingested to counteract euphoric
effects of ecstasy

What rec drug was found in
the characters portrayed in the
movie, Armageddon
A.
B.
C.
D.
X
Kit Kat
Poppers
Ice
Ketamine
Derivative of phencyclidine (PCP),
introduced in the 1960s and used as a
dissociative anesthetic
Special K, “K”, Kit-Kat, Super K
 Jet, Super Acid

Availability




C-III - Injectable prescription
formulation (Ketalar®)
Use has dwindled with advent
of safer, more effective
anesthetics
Common vet agent
Difficult to manufacture and
most often acquired through
diversion of the Rx product
History of Abuse
Believed to have entered rave scene in
mid-1980s
 Originally may have been an adulterant
of MDMA tablets
 As abusers became familiar with the
effects of ketamine, its use as a sole
agent emerged

Street Sales
Injection product (IV or IM)
 Ingestion
 Smoking
 Snorting
 $80.00/gram

Pharmacology
High bioavailability by both IV or IM
route
 Oral doses not as well absorbed and
undergo first pass metabolism
 Interacts with and inhibits NMDA
channels (PCP)

Clinical Effects




Analgesic effects at lower doses, with
amnestic effects at increasing doses
Dramatic feelings of dissociation “floating
over one’s body” into “K-land” or “K-holes”
Visual hallucinations and lack of coordination
are common
Many abusers report effects dependent upon
the setting within which the drug is abused
Amyl and Butyl Nitrites
Volatile nitrite and nitrate derivatives
originally intended to produce
vasodilatory effects on patients with
coronary artery disease.

Poppers
Availability
Originally crushable, mesh
enclosed pearls
 RX product until 1960
when moved to OTC status
 1969 FDA re-instated RX
status subsequent to
reports of abuse
 Banned in 1988

Street Sales
Inhalation
 Sold in small amber glass ampoules
 Typical unit dose for sale contains 10-30
cc of drug
 Cost: $10-20 per ampoule

Clinical Effects
Feelings of a “rush”, warmth, dizziness
 Reduce anal sphincter tone
 Increased sexual intensity
 Methemeglobinemia
 Early association with HIV and KS
 Interaction with PDEs**

Methamphetamine
Crystal, Tina, glass
Speed, Meth, Crank
Historical Aspects
Worldwide
Synthesized in late 1800s and studied in the
1930s
 First epidemic occurred during and after
WWII (1945-1957)
 By 1948 - 5% of Japanese aged 16-25 were
users, restrictions enacted in 1951
 Gradual west to east movement of MA use
from Japan, to Hawaii, to the US west coast
(motorcycle gangs)

Historical Aspects
United States




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1950s: inhalational products available OTC
1960s: popular use of MA/MA derivatives for obesity
1970s: restrictions and underground production increases
1980s: shifts to college students, females, young
professionals
1990s: clandestine labs emerge
1996: Comprehensive Methamphetamine Control Act
2000s: enhanced enforcement and regulation; greater
international (Mex) trafficking – reductions in Mom &
Pop production?
Epidemiology
MA now the most widely abused
substance in world following cannabis
 35 million estimated MA abusers versus
15 million cocaine abusers
 Estimated 5% of US residents have used
MA at least once

Epidemiology
In US from 1992-2002, MA-related
admissions to treatment programs rose
from 10 to 52/100K persons
 Extent of MA abuse seems to be
concentrated in West, Midwest, and
South
 Subpopulations: MSM, homeless, rural
areas

Clandestine labs
“Meth Labs”




Utilize readily available and inexpensive
chemical products and internet recipes to
produce MA
Meth labs carry toxic and explosive risk and
considered hazardous waste sites by
authorities = costly clean-up
Usually designed to be mobile (trailers,
automobile trunks, hotel/motel rooms)
Chemistry beakers, mason jars, coffee filters
Methamphetamine Labs
Cost
Compared to other illicit drugs:
inexpensive
 $25 per 1/4 gram
 $100 per gram
 $1,700 per ounce

Clinical Effects - Acute
“rush” or “flash”
 Flight or fight response
 Increased HR, BP, body temperature
 Euphoria, alertness, energy
 Enhanced sense of well-being/self-esteem
 Increased libido and pleasure from sexual
activity

Clinical Effects - Chronic
Pilot study
 Subjects: 65 active MA abusers (by urine
screen)
 Control: 80 non-abusers
 Poor memory (p=0.03)
 Manual manipulation of information
(p=0.001)

Cho A, et al. J Addic Dis 2002; 21:21-34.
Adverse Effects - Chronic

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Emotional liability (insomnia?)
Paranoid psychosis (insomnia?)
Memory loss (grey matter loss)
Cognitive dysfunction (grey matter loss)
Dermatologic pathology (“crank bugs”)
Burns
Poor dentition – “meth mouth”
Withdrawal/Tachyphylaxis
“meth mouth”
“crank bugs” “meth sores”
“meth-decay”
“meth decay”
HIV
Recreational Drugs
Crossroads
Recreational Drug Use (MA)
Halkitis PN, et al. J Urban Health 2005; 18-25.
450 MSM/bisexual men
 293 (65%) reported MA use in the
previous 4 month time-span
 AA men less likely to report MA use
(p<0.001)
 Mean age of MA users: 33±7.9 years

Recreational Drug Use
Mansergh G, et al. Am J Pub Health 2001.

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Cross-sectional study of 295 gay and bisexual
males in SF Bay Area who attended a circuit
party in previous year.
75% reported use of MDMA
58% reported use of Ketamine
25% reported use of GHB
49% reported having had protected anal sex
and 28% unprotected
Recreational Drug Use
Mansergh G, et al. Klitzman RL, et al. Am J Psychiatry 2000.



Pilot study of 169 gay and bisexual men at
three NYC clubs.
One-third of all respondents reported use of
MDMA at least monthly.
Use of MDMA was statistically significantly
correlated with recent and repeated
unprotected anal sex.
Recreational Drug Use
Colfax GN, et al. J Acquir Immune Defic Syndr 2001.



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Cross-sectional study of gay and bisexual
males in SF to examine prevalence of club
drug use and high risk sex practices during
circuit parties.
80% reported use of MDMA
66% reported use of Ketamine
29% reported use of GHB
21% of HIV+ and 9% of HIV- persons
reported having unprotected anal sex.
Recreational Drug Use
Mattison AM, et al. Journal of Substance Abuse 2001.



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Non-random sample of 1169 circuit party
attendees in 3 separate venues.
50% of respondents reported using MDMA
within last 30 days
Use of MDMA and ketamine were associated
with high risk sexual practices.
Most common reason for attending circuit
party was “to have uninhibited sex.”
Recreational Drug Use
Ostrow D, Plankey M, Cox C, et al. JAIDS 2009;51:349-55.
MACS cohort of HIV-seronegative
MSM 1998-2008 (n=6,972 males)
 Reporting use of both PDEs and other
recreational drugs (n=1,667)

Results
Ostrow D, Plankey M, Cox C, et al. JAIDS 2009;51:349-55.
HIV + (n=57)
HIV – (1610)
No drug use
33%
60%
2 or + URASP
21%
5%
Poppers +/- PDEs
33%
23%
Stimulants
33%
16%
Ethanol (low-mod)
60%
68%
Ethanol (mod- high)
25%
23%
Risk of seroconversion increased from:
2.99 (single drug) [95% CI 1.02-8.76]
8.45 (3 drugs (MDMA, ‘poppers’, PDEs) [95% CI 2.67-26.71]
Results
Ostrow D, Plankey M, Cox C, et al. JAIDS 2009;51:349-55.
Agent
Stimulant
‘Poppers’
PDE
3 drugs
Risk
2.99
3.89
3.44
8.45
Recreational Drug Use
Semple SJ, Strathdee sa, Zians J, et al. BMC Public Health 2010;10:1-6.


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321 participants in a safer-sex intervention
surveyed
Survey: drug use and sexual behavior
Cohort split into groups based on preferred
sexual venue: private (home); commercial
(bathhouse); public (restroom)
Recreational Drug Use
Semple SJ, Strathdee sa, Zians J, et al. BMC Public Health 2010;10:1-6.

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Commercial:
> gay, better educated, ↑ club drugs
High risk sex greatest in commercial and
public groups
Public group:
> alcohol use, heavier overall drug use, ↑
depression
Mean 4.2-7.3 gm of MA in last 30 d
Implications




Rec drugs
inc high risk sexual encounters
inc rate of STIs.
Potential for fatal interactions in HIV seropositive
patients using rec/club drugs.
Potential effects of club drug use on adherence to
antiretrovirals?
Potential deleterious disease-related effects
withstanding issues surrounding other STIs and
ARV adherence
-PEARLS


‘Respect ritonavir’
Start low and have friends nearby
Don’t neglect ethanol (ddI, ABC)

Sildenafil: 25 mg q48h
Vardenafil: 2.5 mg q72h
Tadalafil: 10 mg q 72h

Adherence to ARVs, ancillary meds, appointments, etc.
Don’t forget the needles
Patients use recreational drugs … just ask …


Why Adopt a Broad View of
Adherence?

A broad view of adherence:
– recognizes that adherence is not only about taking
one’s medications
– actively engages patients in health care and
treatment
– values the health impacts of “non-medical”
interventions, including controlled drug use,
stable housing, social supports, harm reduction,
and good nutrition
– improves patients’ self-efficacy
– provides more opportunities for success
Adherence: defined

Any action that improves, supports, or
promotes the health of a person living
with HIV with respect to HIV treatment
and care, including physical, mental,
and psychosocial well-being.
Adherence through HP
“..helping a patient who uses
drugs adhere to a complex
medical regimen can support an
upward spiral of self-esteem and
the adoption of healthier
practices.”
Why focus on adherence in
substance abusers?


There is systemic discrimination against
substance users
– Less access to care
– Less access to ART
– Slower decline in morbidity and mortality
Providers often lack training in the care of
substance users and may have negative
attitudes towards them
Poor Adherence = …
(audience participation time!)
HIV resistance:adherence
Audience poll:
A.
B.
C.
“An individual should be drug free for
one month before they can start
antiretroviral therapy.”
“An individual should be drug free for
three months before they can start
antiretroviral therapy.”
“An individual should be drug free for
six months before they can start
therapy.”
Correct answer:
Yes.
Adherence & Drug of Choice




Heroin: use may be more regimented
– Users may have an easier time w/ adherence
Cocaine/Crack: use may be more sporadic
– Intense mood swings may interfere with
adherence
Methamphetamine: unclear, but use may be more
sporadic and interfere with adherence
Alcohol: may have most negative impact on
adherence due to blackouts and memory loss
HIV, Psyche, Substance Abuse




Up to 50% to 80% of HIV-infected persons are
affected by mental illness.
Triple diagnosis of HIV, substance use, and
mental illness is common.
Up to 80% of HIV-infected patients in
methadone maintenance require psychiatric
consultation for mental illness.
Untreated depression can compromise
medication adherence and make HIV
infection more disabling.
Health Promotion I
Taking all antiretrovirals, on time
exactly as prescribed
 Taking meds to prevent opportunistic
infections
 Keeping regular medical appointments
 Eating a nutritious diet
 Exercising regularly

Health Promotion II
Participating in a drug treatment
program
 Controlling drug use or sobriety
 Practicing safer sex and drug injection
 Taking a multivitamin
 Stopping smoking
 Connecting with a support network

Take Home Points





Individualize treatment plans to each patient’s
needs.
Recognize the specific challenges of working with
HIV infected substance users.
Use knowledge and tools to overcome these
challenges and to advocate for patients.
Consider the boundaries for non-medical providers
offering HIV adherence and health promotion
counseling.
Explore opportunities to link with providers across
disciplines to strengthen adherence support.