Transcript The Role of Pre-Exposure Prophylaxis (PrEP) for the

The Role of Pre-Exposure
Prophylaxis (PrEP) for the
Prevention of HIV
Sarah Kemink, PharmD, AAHIVP
WMSHP Spring Seminar
5/05/2015
HIV
AIDS
• CD4 less than 200 +/- AIDS-defining illness
– Most common:
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Candidiasis of esophagus, bronchi, trachea, or lungs
Pneumocystis jiroveci pneumonia
Cytomegalovirus
Mycobacterium avium
Mycobacterium tuberculosis
Toxoplasmosis
Brief History of HIV
• Late 1970’s – 1996
– Fear, death, misinformation, outrage, civil
disobedience
– Focus on hospice care/treating opportunistic
infections
• 1996 – present
– Combination treatment for HIV
– Disease became chronic, manageable disease
– Focus on compliance and managing adverse effects
Global HIV Infection
• More than 34 million people worldwide living
with HIV
• Annual AIDS-related mortality
– Decreased from peak of 2.2 million in mid-2000s
to 1.7 million in 2011
– Estimated 2.5 million deaths averted since 1995
due to ART
• Only 8 million people with ART coverage
UNAIDS. World AIDS Day Report. 2011.
Global HIV Trends
UNAIDS. World AIDS Day Report. 2011.
Rates of New Infections
• Decreasing – Sub-Saharan Africa, Asia,
Oceania
• Increasing – Eastern Europe, Central Asia,
Middle East, North Africa
• Stable – Latin America, North America,
Western and Central Europe
UNAIDS. World AIDS Day Report. 2011.
Transmission
• Unprotected sex between men who have sex
with men (MSM)
• Unprotected transactional sex in commercial
sex workers (CSW)
• Sharing of contaminated needle-injecting
equipment
UNAIDS. World AIDS Day Report. 2011.
HIV in the United States
• Approximately 1.2 million people with
HIV/AIDS
– Estimated 1 in 6 are undiagnosed
– Approximately 50,000 new infections yearly
• New HIV infections
– MSM account for ~60% of new cases of HIV in US
– Heterosexuals account for ~18% of all new HIV
infections but >80% of new cases in women
CDC. HIV Surveillance Supplemental Report. 2014.
New HIV Infections
CDC. HIV Surveillance Supplemental Report. 2014.
Rates of New Infection
• Stable incidence
• Increasing among specific communities
– African Americans
– Hispanics and Latinos
– MSM
– Injection drug users (IDUs)
CDC. HIV Surveillance Supplemental Report. 2014.
HIV Transmission Risk
Risk per 10,000 Exposures
•Blood Transfusion (9,250)
•Receptive Anal Sex (138)
•Needle-sharing During IV Drug Use (63)
•Needle Stick (23)
•Insertive Anal Intercourse (11)
•Receptive Penile-Vaginal Intercourse (8)
•Insertive Penile-Vaginal Intercourse (4)
•Receptive Oral Intercourse (low)
•Insertive Oral Intercourse (low)
•Biting/Spitting (negligible)
CDC. Transmission Risk – HIV Policies and the Law. 2014.
HIV Prevention
Behavioral Interventions
• Education/Counseling
• Screening for Behavioral Risk Factors
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Number/sex of partners
HIV status of partners
Types of sexual activities
Barriers to abstinence
• Condom use
• Male Circumcision
• Screening and Treatment of STI’s
Treatment as Prevention
HTPN 052
Cohen, et al. NEJM 2011; 365: 492-505
Perinatal Prophylaxis
• Use of ART to prevent
HIV transmission from
mother-to-child
• Incidence reduced by
40%
– 570,000 in 2003
– 330,000 in 2011
UNAIDS. World AIDS Day Report. 2011.
Post Exposure Prophylaxis (PEP)
• Use of ART after exposure
– accidental needlestick
– sexual assault
• Not as effective as prevention of HIV
transmission by avoiding exposures
• Less likely to be effective if initiated >72 hours
after exposure
• Not likely to benefit persons with frequent,
repeated exposures
Kuhar, et al. Inf Control 2013; 34(9): 875-92
Pre-Exposure Prophylaxis (PrEP)
• Temporary
• Prevention of HIV during periods of high-risk
behaviors
• Limit infected cells below a theoretical
threshold under which infection cannot be
established
• Block viral replication to allow host responses
to clear infection
CDC. PrEP Guidelines. 2014.
Ideal PrEP Medication
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High potency against HIV
Simple dosing schedule
Low rates of adverse events
Low frequency of drug-induced resistance
High genital and rectal tissue
concentrations
• Active in resting CD4 cells and during preintegration phase
Derdelinckxl, et al. PLoS Med. 2006; 3(11): e454
PrEP Options
• Tenofovir (Viread)
– Available as oral tablet or 1% vaginal gel
• Tenofovir disoproxil fumarate(TDF)/
Emtricitabine (ETV) (Truvada)
– Available as oral tablet
CDC. PrEP Guidelines. 2014.
TDF/FTC (Truvada)
• Nucleotide/nucleoside reverse transcriptase
inhibitors (NRTI’s)
• Long intracellular half-lives
• High genital tissue concentrations
• Active in both active and resting CD4 cells
• Few drug interactions
• Both components active against Hepatitis B
Truvada® [package insert]. Foster City, CA; Gilead Sciences, Inc; 2013
TDF/FTC (Truvada)
• Common adverse events:
– GI, tiredness, headache
– Typically short-term and mild
• Rare adverse events:
– Lactic acidosis – rare case reports
– Renal dysfunction
• Acute risk = 1 – 4%
– Decrease bone mineral density
• 3-4% decline
Truvada® [package insert]. Foster City, CA; Gilead Sciences, Inc; 2013
TDF/FTC Resistance
• FTC resistance
– M184V
– Rapidly selected (within 15
days)
Hurt, et al. Clin Inf Dis 2011; 53(12): 1265-70
• TDF resistance
– K65R
– May take up to 28 days
– Less likely if taking TDF/FTC
Comparative effectiveness of current
HIV prevention strategies
Karim , et al. Lancet 2011; 378: e23-5
FEM-PrEP
• 2,120 women in Africa
• Trial stopped early for futility
• Compliance
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Self-reported adherence: 95%
Pill counts: 88%
Drug level testing: drug detected in < 40% participants
High pregnancy rates in women on oral contraceptives
• Patient motivation is crucial!
– 70% perceived themselves to be at no or low risk for
HIV infection
Van Damme, et al. NEJM 2012; 367(5): 411-22
TDF2
• 1,219 heterosexual participants in Africa
• 62% overall efficacy
– 49% in females, 80% in males
• Compliance
– Self-reported: 84%
– Significantly lower serum drug levels in infected
participants vs. noninfected
Thigpen, et al. NEJM 2012; 367(5): 423-34
Partners PrEP
• 4758 heterosexual HIV serodiscordant couples
in Africa
• 66% efficacy in women, 84% efficacy in men
• Compliance
– Pill counts: 97%
– Drug level testing:
• Infected participants: <30% had detectable levels of
TDF/FTC
• Uninfected participants: >80 % had detectable levels of
TDF/FTC
Baeten, et al. NEJM 2012; 367(5): 399-410
iPrEx
• 2,499 MSM, transgender women in 11 sites
(US, South America, Africa, Thailand)
• 44% reduction in HIV Infection Rate
• Compliance
– Pill use > 50% = risk reduction by 50%
– Pill use > 90 % = risk reduction by 73%
• Case control study
– 92% reduction with detectable levels of TDF
Grant, et al. NEJM 2010; 363(27): 2587-99
iPrEx OLE
Grant, et al. Lancet Inf Dis 2014; 14: 820-29
CDC PrEP Guidelines - 2014
CDC. PrEP Guidelines. 2014.
PrEP Eligibility
• HIV NEGATIVE patients
–Serodiscordant couples
–High Risk MSM
–High Risk Heterosexual Men/Women
–High Risk Injection Drug Users (IDU)
CDC. PrEP Guidelines. 2014.
Risk Determination
CDC. PrEP Guidelines. 2014.
Pre-Treatment Testing
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HIV negative test result
Rule out acute HIV infection
Normal renal function (serum creatinine)
Documented Hepatitis B infection or
vaccination status
• Bacterial STI testing
– Gonorrhea
– Chlamydia
– Syphillis
CDC. PrEP Guidelines. 2014.
HIV Testing
• Western Blot
– No longer recommended
• 2nd/3rd Generation Antibody
– May miss acute HIV infection
• HIV RNA (Viral Load)
– Not covered by many insurance plans unless HIV
antibody positive
• 4th Generation Antigen/Antibody Testing (p24
Antigen)
– Recommended per updated CDC guidelines in 2014
– Not widely available
CDC. PrEP Guidelines. 2014.
Action for Aids. 2014.
CDC. PrEP Guidelines. 2014.
Prescribing PrEP
• TDF/FTC (Truvada)
– One tablet daily
– 90 day prescription only
– Renew every 3 months
ONLY after negative HIV
test + compliance
assessment
CDC. PrEP Guidelines. 2014.
Patient Counseling/Education
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Sexual risk reduction counseling
Medication education
Adherence counseling
Provide condoms
CDC. PrEP Guidelines. 2014.
Baseline Compliance
Follow-up and Monitoring
• Every 3 months:
– HIV Test
– Adherence Counseling
– Behavioral Risk Reduction Support
– Adverse Event Assessment
– STI Symptom Assessment
– Pregnancy Test (if appropriate)
CDC. PrEP Guidelines. 2014.
Ongoing Compliance
• Every 3 months
– Evaluate current medication list for interactions
– Ongoing compliance assessment
Ongoing Compliance
Follow-up and Monitoring
• Every 6 months:
– Assess Renal Function
• Metabolic panel
• Urinalysis
– Test for Bacterial STI’s
CDC. PrEP Guidelines. 2014.
PrEP Barriers
• Patient Stigma
• Patient Motivation
• Lack of Access/Cost of Treatment
– Insured/Uninsured
– Copay/Deductible Cost
Stigma
• Primarily within/among/against the gay
community
• PrEP is only for people who are promiscuous
– PrEP will lead to increased risky behaviors such as
decreased condom use
Condom Use and PrEP
• 70 - 80% efficacy in preventing HIV
• CDC study in 2013 showed declining condom
use among gay men prior to PrEP (48% in
2005, 57% in 2011)
• iPrEx
– No change in condom use if patients thought they
were on placebo vs. treatment
• Both iPrEx and Partners PrEP found
DECREASING risk behavior over time
CDC. MMWR 2013; 62(47): 958-62
Grant, et al. NEJM 2010; 363(27): 2587-99
Baeten, et al. NEJM 2012; 367(5): 399-410
PrEP Barriers
• Patient Stigma
• Patient Motivation
• Lack of Access/Cost of Treatment
– Insured/Uninsured
– Copay/Deductible Cost
Patient Motivation
• Unwillingness to take pill daily
• Fear of side effects
• Lack of perceived risk
– False belief that HIV is an older generation’s issue
– Avoiding sexual partners with known HIV
PrEP Barriers
• Patient Stigma
• Patient Motivation
• Lack of Access/Cost of Treatment
– Insured/Uninsured
– Copay/Deductible Cost
PrEP Cost
• Manufacturer patient
assistance program
– Uninsured patients
• High copay cost:
– Manufacturer copay card
available
– Covers up to $300/month
for Truvada
• High deductible
– Patient Access Network
– Will cover $4,000/year for
eligible patients (500%
federal poverty level)
Important Points
• Reserved for high-risk individuals
– Serodiscordant couples, IDU, high-risk sexual
behavior
• Adherence is crucial for prevention
• Significant barriers to treatment
– Need for increased education for providers and
high-risk patients
On Demand PrEP
• ANRS IperGay:
– 2 tablets 2 - 24 hours prior to sex
– 1 tablet 24 hours after sex
– 1 tablet 48 hours after initial dose
– 86% reduction in HIV
– Median of 16 tablets taken per month
Molina, et al. CROI 2015. Abstract 23LB.
Pipeline Medications
• TAF – Tenofovir alafenamide fumarate
– Prodrug of tenofovir
– Less serum drug exposure
– Can be dosed at 1/10th dose of TDF
– Decreased renal/bone long term side effects
– Low levels in genital tissues
Horn, et al. HIV Preventative Technologies 2014; 55-82
Pipeline Medications
• Oral
– Maraviroc (monotherapy or combination) (phase
II)
• Long-Acting Injectables
– Cabotegravir (phase II)
– Rilpivirine LA (phase II)
• Vaginal Rings
– Dapivirine vaginal ring (phase III)
Horn, et al. HIV Preventative Technologies 2014; 55-82
UNAIDS “Getting to Zero”
Goals for HIV Prevention
• Sexual transmission of HIV reduced by half,
including among young people, men who have
sex with men and transmission in the context
of sex work
• Vertical transmission of HIV eliminated and
AIDS-related maternal mortality reduced by
half
• All new HIV infections prevented among
people who use drugs
UNAIDS. Getting to Zero: 2011-2015 Strategy.
Questions?
Question 1
• Which of the following patients would be
candidates for PrEP?
– 27 year old MSM with ongoing high risk sexual
behavior of unprotected anal sex
– 30 year old nurse working in an HIV clinic who
administers vaccines and other injections to HIV seropositive patients
– 35 year old HIV sero-negative man in a monogamous
relationship with his sero-positive husband (husband
has undetectable HIV viral load)
– A and C
– All of the above
Question 2
• Which of the following laboratory tests are
recommended prior to initiating PrEP with
TDF/FTC (Truvada)?
– Baseline third or fourth generation HIV test
– Serum Creatinine
– Serology for Hepatitis B and C
– STI screening
– All of the above
Question 3
• Which of the following are barriers to starting
PrEP therapy?
– Treatment coverage/cost
– Stigma
– Patient motivation
– All of the above