Transcript PrEP - WordPress.com

Elliot DeHaan, MD
Clinical Assistant Professor
Division of Infectious Diseases/S.T.A.R. Program
SUNY Downstate Medical Center
November 13, 2014
 The presenter has no significant disclosures.
 Discuss the epidemiology of new HIV infections
 Discuss evidence behind Pre-Exposure Prophylaxis (PrEP)
 Understand current guidelines (CDC, NYS DOH) for PrEP
 Review research regarding provider and patient attitudes
 Understand Payment options for PrEP
 40 states and 5 US dependent areas
25,000
Male-to-male sexual contact
Diagnoses (n)
20,000
15,000
Injection drug use
Male-to-male sexual contact
and injection drug use
10,000
Heterosexual contact*
5000
Other†
0
2006
2007
2008
Yr of Diagnosis
2009
*Heterosexual contact with a person known to have or to be at high risk for HIV infection.
†Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or identified.
Note: Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically
adjusted to account for reporting delays and missing risk-factor information but not for incomplete reporting.
CDC. HIV surveillance in men who have sex with men (MSM). 2011.
 40 states and 5 US-dependent areas
35-44
7000
Diagnoses (n)
6000
25-34
13-24
5000
45-54
4000
3000
2000
55
1000
0
2006
2007
2008
Yr of Diagnosis
2009
Note: Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically
adjusted to account for reporting delays and missing risk-factor information but not for incomplete reporting.
CDC. HIV surveillance in men who have sex with men (MSM). 2011
80%
77%
66%
89%
77%
Multiplies
to 28%
850,000 HIV+ Americans (72%) lack viral control
 A more recent MMWR report found in a survey of
421,186 adults at HIV clinics from Jan-April 2009 in the
US and Puerto Rico
 88.7% received ART
 71.6% viral load <200 copies/mL last visit
Blair JM, Fagan JL, Frazier EL et al. MMWR 2014; 63(ss05): 1-22
Total HIV-1 Transmission Events: 39
(4 in immediate arm and
35 in delayed arm; P < .0001)
Linked
Transmissions: 28
Delayed
Arm: 27
Immediate
Arm: 1
P< .001
Cohen MS, et al. N Engl J Med. 2011;365:493-505.
Unlinked or TBD
Transmissions: 11
Single transmission in patient in
immediate HAART arm believed
to have occurred close to time
therapy began and prior to
suppression of genital tract HIV

Observational study of rate of HIV
transmission in heterosexual and
MSM serodiscordant couples (N = 767
couples)
0
HT♀ Vaginal sex with ejaculation
HT♂
– HIV+ partner on suppressive ART
– Condoms not used



Risk Behaviors, %
20 40 60 80 100
Vaginal sex
Receptive anal sex
MSM
Receptive anal sex with
ejaculation
Only insertive anal sex
Analyses: 6-monthly risk behavior
questionnaire, HIV-1 RNA (HIV+
persons), HIV test (HIV-negative
persons)
Rate of Within-Couple Transmission Events Per
100 CYFU, % (95% CI)
4
0
1
2
3
HT♀
Endpoint: phylogenetically linked
transmissions
No linked transmissions recorded in
any couple during study period
Rodger A, et al. CROI 2014. Abstract 153LB.
Reproduced with permission.
HT♂
Vaginal sex with ejaculation
(CYFU = 192)
Vaginal sex (CYFU = 272)
Receptive anal sex with
ejaculation (CYFU = 93)
MSM Receptive anal sex without
ejaculation (CYFU = 157)
Insertive anal sex (CYFU = 262)
Estimated rate
95% CI
Undiagnosed HIV
Not linked to care
Not retained in care
ART not required
ART not utilized
Viremic on ART
Undetectable
HIV-1 RNA
Number of Individuals
1,200,000
1,000,000
800,000
600,000
400,000
200,000
66%
19%
22%
Current
DX
90%
34%
28%
Engage
90%
Treat
90%
21%
0
VL < 50
Dx,
in 90% Engage, Tx,
and VL < 50
in 90%
Answer: Treatment AND Prevention
Gardner EM, et al. Clin Infect Dis. 2011;52:793-800.
 Phase 3, double-blind, randomized, placebo-controlled, 11
sites in 6 countries
 Adult HIV-MSM or transgender women in the US, Peru,
Ecuador, Brazil, Thailand, South Africa
 Two study arms:
 TDF/FTC (300mg/200mg) orally once daily
 Placebo
 Primary Outcome: Prevention of HIV
Grant RM, Lama JR, Anderson PL, et al. N Engl J Med 2010;363:2587-2
Inclusion Criteria





Male sex at birth
Age 18+
HIV-seronegative
High risk for HIV acquisition
Lab inclusion criteria:
Exclusion Criteria
 Serious and active illness:
 Diabetes, TB, Cancer
 Active substance abuse
 Nephrotoxic agents
 Pathological bone fractures
 CBC, BMP, LFTs
Grant RM, Lama JR, Anderson PL, et al.N Engl J Med 2010;363:2587-2
44% reduction,
P=0.002
95% CI (15-63%)
Grant RM, Lama JR, Anderson PL, et al. N Engl J Med 2010;363:2587-2
Grant RM, Lama JR, Anderson PL, et al. N Engl J Med 2010;363:2587-2
 TDF/FTC was well tolerated
 Nausea (2% versus <1%) and weight loss >5% (2% versus
1%) were more common among those taking medication
than those on placebo
 No differences in severe (grade 3) or life-threatening
(grade 4) laboratory abnormalities were observed
between groups
 No drug resistant virus was found in the 100 participants
infected afterenrollment
Grant RM, Lama JR, Anderson PL, et al. N Engl J Med 2010;363:2587-2
Group
Drug Detection
HIV Infections
Incidence Density
Placebo
No
64
3.86
FTC/TDF
No
33
4.04
Yes
3
0.35
Relative Rate Reduction by use of FTC/TDF
Grant RM, Lama JR, Anderson PL, et al.N Engl J Med 2010;363:2587-2
91%
iPrEX OLE: 100% Adherence With Daily PrEP Not
Required to Attain Full Benefit
HIV Incidence per
100 Person-Yrs
5
HIV Incidence and Drug Concentrations
< 2 Tablets/Wk 2-3 Tablets/Wk
4-6 Tablets/Wk
7 Tablets/Wk
4
3
Off PrEP
2
1
On PrEP
0
0LLOQ
350
Follow-up,%
26
Risk Reduction,%
44
95% Cl, %
-31 to 77

500
700
1000
1250
1500
TFV-DP in fmol/punch
12
21
12
84
100
100
21 to 99
86 to 100 (combined)
TFV-DP: tenofovir diphosphate (measurable tenofovir in dried blood spots)
Grant R, et al. AIDS 2014. Abstract TUAC0105LB. Graphic used with permission.
 4758 HIV-1 serodiscordant heterosexual couples in Kenya and
Uganda
 Three study arms:
 TDF (300 mg) orally once daily
 TDF/FTC (300mg/200mg) orally once daily
 Placebo
 Primary Outcome: Prevention of HIV-1 infection in HIVnegative partner
Baeten JM, Donnell D, Ndase P et al. N Engl J Med 2012;367:399-410
Baeten JM, Donnell D, Ndase P et al. N Engl J Med 2012;367:399-410
67% efficacy TDF
75% efficacy TDF-FTC
Baeten JM, Donnell D, Ndase P et al. N Engl J Med 2012;367:399-410
Baeten JM, Donnell D, Ndase P et al. N Engl J Med 2012;367:399-410
 1219 HIV-uninfected adults
 Randomized to
 TDF-FTC
 Placebo
Thigpen MC, Kebaabetswe PM, Paxton LA, et al. New Engl J Med 2012;
367(5): 423-434
Thigpen MC, Kebaabetswe PM, Paxton LA, et al. New Engl J Med 2012; 367(5): 423-434
 Phase 3, randomized, double-blind, placebo-controlled trial
 2120 women from Tanzania, Kenya, and South Africa
 Two study arms:
 TDF/FTC (300mg/200mg) orally once daily
 Placebo
 Primary Outcome: Prevention of HIV-1 infection
 NO EFFICACY WAS OBSERVED
 Lack of difference driven by poor adherence to study drug
Damme LV, Corneli A, Ahmed K, et al. New Engl J Med 2012; 367(5): 411-422
 Randomly selected 150 participants from 3 study sites to
determine drug adherence at 4 week intervals
 Plasma tenofovir level
 Intracellular tenofovir-diphosphate
 Assigned an adherence composite score
Corneli AL, Deese J, Wang M, et al. J AIDS 2014;66(3):324-331
Corneli AL, Deese J, Wang M, et al. J AIDS 2014;66(3):324-331
Phase IIB placebo-controlled trial of > 5000 women in South Africa, Uganda, and
Zimbabwe of daily oral TDF, daily oral TDF/FTC, daily vaginal TFV 1% gel as PrEP
DSMB stopped daily oral TDF arm in September 2011 and daily vaginal gel arm in November
2011, both for lack of efficacy; daily oral TDF/FTC arm continued
334 infections seen across 5 arms; 22 infected at enrollment
Primary Efficacy Results (mITT)
TDF*
(n = 1007)
Oral
Placebo*
TDF/FTC
(n = 1003)
Oral
Placebo
TFV Gel
(n = 1007)
Gel
Placebo
Infections, n
52
35
61
60
61
70
Infections/100 PY
6.3
4.2
4.7
4.6
5.9
6.8
Protective Efficacy vs Placebo
HR (95% CI)
P value
1.49 (0.97-2.30)
1.04 (0.7-1.5)
0.85 (0.6-1.2)
.07
> .2
> .2
*Censored when sites took women off TDF and TDF placebo. N = 1009.
Marrazzo J, et al. CROI 2013. Abstract 26LB.
 Despite high self-reported
adherence, < 40% of women had
detectable plasma TFV at first
study visit
Pts With Detectable TFV* (%)
Plasma TFV Detection
in Random Cohort Sample
100
TDF/FTC
TDF
TFV 1% gel
80
 TFV detected in mean of ≤ 30%
of samples in each arm
60
40
– ≥ 50% of women in each arm
had no TFV detected in any
sample
20
0
1
n = 135
n = 147
n = 166
2
123
119
156
3
4
Quarterly Visits
111
80
107
117
56
82
*Level of TFV detection: ≥ 0.3 ng/mL.
5
6
95
28
52
61
16
30
 TFV detection less likely if
unmarried, younger than 25 yrs,
partner younger than 28 yrs
– Highest rates of HIV acquisition
in unmarried, younger than
25 yrs
Marrazzo J, et al. CROI 2013. Abstract 26LB. Graphic used with permission.
 Phase III, randomized, double-blind, placebo-controlled trial
– HIV-uninfected IDUs (N = 2413) received TDF or placebo
– DOT at drug treatment clinics between 2005 and 2010
 Significantly fewer new infections with TDF vs placebo (0.35/100
PY vs 0.68/100 PY; P = .01)
– Overall efficacy: 49%
– Detectable TDF at study end: 74%
 Higher adherence associated with greater efficacy
 Safety and tolerability similar to other TDF-containing PrEP trials
Choopanya K, et al. IAS 2013. Abstract WELBC05.
100
84
80
Efficacy (%)
68
60
49
54
72
58
40
20
0
mITT
> 67
> 75
> 90
> 95
Adherence (%)
Choopanya K, et al. IAS 2013. Abstract WELBC05. Graphic used with permission.
> 97.5
Study Name
Population
N
Results
Partners PrEP
Heterosexual
couples
4,758
TDF: 67%
efficacy
FTC/TDF: 75%
efficacy
TDF2 Study
Heterosexual
Men and Women
1,219
FTC/TDF: 62%
efficacy
iPrEx
MSM
2,499
FTC/TDF: 44%
efficacy
FEM-PrEP
Women
1,951
FTC/TDF:
futility
VOICE
Women
5,029
TDF, TDF/FTC,
Vaginal
TFV gel: futility
Thai IVDU
IVDU
2,413
TDF: 49%
efficacy
Kahle E, et al. 19th IAC; Washington, DC; July 22-27, 2012; Abst. TUAC0102
November 2010
iPrEx
August 2012
TDF2
Partners PrEP
July 2012
FEM-PrEP
January 2011
CDC Interim Guidance:
PrEP for MSM
July 2012
FDA Approval
TDF/FTC PrEP
June 2013
Bangkok TDF Study
March 2013
VOICE
June 2013
CDC Interim Guidance:
PrEP for IDU
January 2014
NYS AIDS Institute
August 2012
CDC Interim Guidance:
PrEP for
heterosexuals
Guidance for PrEP
May 2014
US Public Health Service
Clinical Practice
Slide courtesy of Katherine Marx, MS, MPH, FNP, NYNJ AETC Guideline for PrEP
 PrEP should not be offered as a sole intervention and should
include counseling and education about:
 Consistent and correct condom use
 Safer-sex practices and risk-reduction counseling
 Intravenous drug use (IVD), harm reduction methods
 Adherence to PrEP
 Importance of frequent HIV testing and screening of STIs
that can facilitate HIV transmission
 For sero-discordant couples, the importance of
suppressive ART for HIV-infected partners
http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-the-use-of-preexposure-prophylaxis-prep-to-prevent-hiv-transmission/
 PrEP is indicated for individuals who have a documented
negative HIV test and are at ongoing, high risk for HIV
infection
 Negative, HIV test result needs to be confirmed as close to
initiation of PrEP as possible
 PrEP is not meant to be used as a lifelong intervention, but
rather as a method of increasing prevention during “high risk”
periods
http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-the-use-of-preexposure-prophylaxis-prep-to-prevent-hiv-transmission/
MSM who engage in unprotected anal
intercourse 1,2
Stimulant drug use, especially
methamphetamine 4
Individuals in a sero-discordant sexual
relationship, especially during attempts to
conceive
Individuals with ≥ 1 ano-genital STI per year5
Transgendered individuals
Individuals who have been prescribed nPEP
with continued high-risk behavior or
multiple courses 6
IDUs, including injecting hormones 3
Individuals engaging in transactional sex
1. Smith DK, et al. Development of a clinical screening index predictive of incident
HIV infection among men who have sex with men in the United States. J Acquir
Immune Defic Syndr 2012;60:421-427.
2. Grov C, et al. HIV risk in group sexual encounters: An event-level analysis from
a national online survey of MSM in the U.S. J Sex Med 2013;10:2285-2294
3. Choopanya K, et al. Antiretroviral prophylaxis for HIV infection in injecting drug
users in Bangkok, Thailand.
4. Zule WA, et al. Methamphetamine use and risky sexual behaviors during heterosexual
encounters. Sex Transm Dis2007;34:689-694
5. Menza TW, et al. Prediction of HIV acquisition among men who have sex with men. Sex
Transm Dis 2009;36:547-555.
6. Heuker J, et al. High HIV incidence among MSM prescribed postexposure prophylaxis,
2000-2009: Indications for ongoing sexual risk behaviour. AIDS 2012;26:505-512
.
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


Documented HIV infection
CrCl<60 mL/min
Lack of readiness to adhere to daily regimen
NOTE: lack of condom use is NOT a
contraindication to PrEP
http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-the-useof-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
 Symptoms of Acute HIV
Infection
 Febrile, “flu”, or “mono”-like
illness in last 6 weeks
 Medication List
 Substance Use and Mental
Health Screening
 Knowledge about PrEP
 Patient understanding and
misconceptions
 Health Literacy
 Readiness and Willingness to
adhere to PrEP
 Primary Care
 Does the patient have a PCP?
 Partner Information
 Determine status of partners
 Domestic Violence Screening
 Housing Status
 Means to Pay for PrEP
 Is patient insured?
 Reproductive Plans (for
Women)
http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-the-useof-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
•
•
•
•
•
HIV Test
• Obtain 3rd or 4th generation HIV test
• Perform viral load test for HIV for:
• Patient with sxs of AHI or whose HIV AB is negative but reports
unprotected sex in last month
Basic Metabolic Panel
• Do not start PrEP if CrCl <60 mL/min
Urinalysis
• Identify pre-existing proteinuria
Serology for Hep A, B and C (Immunize for A and B if not immune)
• Screen for sexually transmitted infections, GC and chlamydia (genital, rectal,
pharyngeal)
• RPR for syphilis
• Consider vaccinations for HPV and meningococcus, if indicated
Pregnancy Test
http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidancefor-the-use-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
•The first prescription of TDF/FTC should only be for 30 days
•At the 30 day visit (after assessing adherence, tolerance and
commitment), a prescription for 60 days may be given
•Creatinine and CrCl for patients with borderline renal function or at
increased risk for kidney disease (>65 years of age, black race, HTN or
DM)
•After 3 month visit, prescriptions can be given for 90 days provided
that patient is adherent
•Patient should then return for 3-month visits for HIV testing and other
assessments:
http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-the-use-of-preexposure-prophylaxis-prep-to-prevent-hiv-transmission/
Tellalian et al. AIDS Patient Care and STDs. October 2013, 27(10): 553-559.




Survey of ID physicians (n=573)
74% supported PrEP
9% have actually prescribed PrEP
14% would not provide PrEP
Karris et al. (2014). Clin Infec Dis 58(5): 704-12.
 One survey (n=86, 56% male, 70% heterosexual) showed
that a majority (94%) of participants were willing to use
PrEP
Tripathi, et al. (2013). Southen Med J Oct;106(10):558-64
 In a survey of men visiting an online gay social
networking site (n=9,179) 1.2% reported using PrEP
Mayer, et al. (2014). Early Adopters: Correlates of
chemoprophylaxis use in an online sample of US Men who have
sex with Men. CROI 2014 Abstrat 952
 Most insurances paying for PrEP including Medicaid HMOs
 Prior authorizations
 Truvada® for PrEP Medication Assistance Program
 200% federal poverty threshold
 ICD09 codes
 V69.2 High risk sexual behavior
 V01.79 Exposure to other viral diseases
 CPT codes
 99401-99404 (Preventive Counseling 15/30/45/60 mins)
 Targeting high risk populations
 Partners of known HIV-infected persons
 Includes pregnant women
 MSM and TG women as per NYS DOH guidelines
 IVDs
 Other
 Discuss a case and possible referral?
 Elliot DeHaan, MD (718) 270-2471
 [email protected]
 PrEP as daily fixed-dose tenofovir-emtricitabine has a strong
evidence basis in multiple populations of individuals at highrisk for HIV-infection (heterosexual, MSM, IVDs)
 Needs to be prescribed as part of a comprehensive
prevention plan that includes use of condoms, harm
reduction for IVDs
 Strong consideration should be given to its use in populations
as defined by NYS DOH and the CDC
 Both providers and patients are open to the idea of its use
 Insurance plans are covering the cost of drug, though prior
authorization may be necessary