This is a training on PrEP (pre-exposure prohylaxis) for HIV prevention, designed for people who work in the HIV prevention field. The training is designed by AIDS Foundation of Chicago's Project Ready, Set, PrEP! (RSP!). For more information on PrEP, visit the project's blog at www.myprepexperience.blogspot.com.

1. Welcome!
Project RSP! training

2. Our time together
• What is Project RSP?
• What do YOU think about PrEP?
• Overview of ARV-based prevention
• Understanding PrEP
– What is PrEP?
– What is research telling us about PrEP?
– How do you use PrEP?
– How do you get PrEP?
• Talking to clients about PrEP
2

3. 3

4. • Trainings: Help Chicago providers, educators, and others
working directly with our community to understand PrEP
and what it means for us and HIV prevention.
• Community forums: Interactive and fun discussions done
“talk show” style – first is May 22, 2013 at Center on
Halsted, 6p – 9p, please join us.
• Give voice/provide facts: Platform for PrEP users to share
experiences, interested individuals to get info –
click myprepexperience.blogspot.com.
4

5. 5

6. Your primer on ARV prevention
6

7. A growing prevention toolkit
• Improved ARV therapy
• Treatment for
opportunistic infections
• Basic care/nutrition
• Prevention for positives
• Education & rights-focused
behavior change
• Therapeutic vaccines
Prior to exposure Point of transmission Treatment
•Male and female
condoms and lube
•ARV treatment to
prevent vertical
transmission (PMTCT)
•Clean injecting
equipment
•Post-exposure
prophylaxis (PEP)
•Vaginal and rectal
microbicides
•Rights-focused
behavior change
•Voluntary counseling
and testing
•STI screening and
treatment
•Male medical
circumcision
•Preventive Vaccines
•Pre-exposure
prophylaxis (PrEP)
7

8. 8

9. Prevention Paradigm 2013 and
beyond
Different Strokes for Different Folks
Method Contraception HIV Prevention
Behavior ✓ ✓
Barrier Methods ✓ ✓
Gels ✓
Rings ✓
Oral pill ✓ ✓
Injectables ✓
Implants ✓
Surgical procedures ✓ ✓
Treatment ✓

10. What is ARV-based prevention?
• Strategies that use HIV treatment
drugs (antiretrovirals or “ARVs”) to
prevent HIV infection
– TLC+ (testing, linkage to care, plus
treatment)
– ARV-based microbicides
– PEP (post-exposure prophylaxis)
– PrEP (pre-exposure prophylaxis)
10

11. Other terms in use
TLC+
• Treatment as
Prevention
(TasP)
• Test and Treat
(TnT)
• Treatment for
Prevention
(T4P)
PrEP
• Oral
Prevention
• Oral PrEP
Microbicides
• Topical PrEP
• Topical
Prevention
11

12. Pills, lubes, and more pills
PrEP
Microbicides –
rectal, vaginal
TLC+
12

13. 13

14. • Provide ARV treatment to HIV+ people
who accept it voluntarily
– Improve treatment access for HIV+
– Offer treatment earlier in the course
of the disease
– Reduce community viral load
– Reduction in onward HIV
transmissions
Testing, linkage to care, plus treatment – TLC+
14

15. What research says about TLC+
HPTN 052 trial
demonstrated 96%
reduction in sexual
transmission of HIV
between (mostly)
heterosexual
serodiscordant
couples.
www.ncbi.nlm.nih.gov/pmc/articles/PMC3486734/
Limitation – how applicable for
gay men or IDU?
15

16. ARV-based microbicides
• Substances in development that would
reduce sexual transmission of HIV
• Applied rectally or vaginally
– Gels, vaginal rings
• Future formulations could include
films, rectal enemas
• Microbicides don’t have to be ARV-
based, though most products
currently under investigation are
• Other compounds have been tested;
scientists are exploring non-ARV
formulations
16

17. Microbicides, the research says:
• CAPRISA 004 – reported 2010, first to show
efficacy
• 1% tenofovir reduced HIV in women by
39%, in South Africa
• Tested product efficacy before and after sex
• VOICE – reported 2013, no efficacy, low
adherence
– African women in Uganda, S. Africa,
Zimbabwe
– Daily use 1% tenofovir gel, tenofovir tablet,
Truvada tablet
• FACTS – confirmatory trial underway,
CAPRISA protocol, S. Africa
17

18. Rectal microbicide trial
• MTN 017– first Phase II ever, safety and
acceptability (not efficacy)
– Modified version of tenofovir gel (booty
friendly) and Truvada tablet
– Open-label, cross-over design
• Daily gel, gel w/sex, daily Truvada (8wks ea)
– 186 gay men, transgender women
– US, Peru, South Africa, Thailand
• US = Pittsburgh, Boston, San
Francisco, Puerto Rico
– Starting later this year (US sites in
June?) 18

19. 19
YouTube
http://tinyurl.com/RectalRevEnglish
http://tinyurl.com/RectalRevSpanish

20. Post-exposure prophylaxis (PEP)
Provide 3-drug regimen of ARVs after HIV
exposure to stop infection
• Typically offered to health care
providers exposed to HIV via needle
stick
• nPEP – offered for non-occupational
exposure, sexual exposure, injection
drug use
• Must be taken within 72 hours of
initial exposure, small window
• ARVs must be taken for 28 days
20

21. Accessing PEP
• Any doctor is able to prescribe
• HIV docs the best to manage PEP, most likely to
prescribe
• Available at no cost through CORE Center’s walk-in
clinic M-F 8:30am-3:30pm, 312.572.4700
• Person must come in weekly for meds and monitoring
• ERs can/do start PEP, but only provide 3 days of meds
– Necessary that person is engaged with provider for
duration of regimen for monitoring and HIV testing
21

22. What is
PrEP?*
*pre-exposure prophylaxis
22

23. Hold up, what is prophylaxis?
• Prophylaxis is simply the provision of
medications prior to germ or virus
exposure to prevent infection.
• This is not a new concept.
• This is not a new practice.
• Example: taking malaria drugs
before traveling to countries with
high malaria incidence
• What are examples of similar concepts?
23

24. So, what is PreP?
• PrEP involves an HIV-negative person taking ARVs to reduce
risk of infection BEFORE HIV exposure. It prevents HIV from
reproducing in a person’s body.
• In current approved formulation, PrEP is taken in a single pill
once a day, every day (Truvada).
• Truvada is currently the only combination of drugs approved
by the FDA for PrEP.
• Truvada is a combination of tenofovir disoproxil fumarate
(aka tenofovir or TDF) and emtricitabine.
24

25. PrEP Truvada
• PrEP will not always be only Truvada
• Researchers are currently exploring
other ARV drugs that could also be used
for PrEP
• For instance, the ARV drug Maravoric
(brand name Selzentry) is currently in
clinical trials as a potential PrEP drug
• Scientists are also researching the
possibility of intermittent use of PrEP
– May not have to be taken daily
– PrEP could be delivered via injection, and
could be longterm
25

26. Dateline: July 16, 2012
Today, the US Food and Drug Administration
approved Truvada (emtricitabine/tenofovir
disoproxil fumarate), the first drug approved
to reduce the risk of HIV infection in
uninfected individuals who are at high risk of
HIV infection and who may engage in sexual
activity with HIV-infected partners. - FDA
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312210.htm
26

27. • Truvada is approved for use as part of a comprehensive HIV
prevention strategy that includes other prevention methods, such
as safe sex practices, risk reduction counseling, and regular HIV
testing. - FDA
– Must be confirmed HIV-negative before prescription
– FDA required development of Risk Evaluation and Mitigation
Strategy (REMS) for use of Truvada as PreP to ensure safe use
• Medication guide
• Community education
• Provider training
• Implementation
Dateline: July 16, 2012
27

28. • Dear Healthcare Provider Letter
• Training Guide for Healthcare Providers
• Important Safety Information for Healthcare Providers
• Safety Information Fact Sheet
• Agreement Form
• Checklist for Prescribers
• Medication Guide
• Important Safety Information for Uninfected Individuals
• Full Prescribing Information
• www.truvadapreprems.com
28
What’s in the REMS?*
28*Risk Evaluation and Mitigation Strategy

29. CDC Interim Guidance on PrEP - 2011
Before Starting PrEP
• Conduct HIV antibody
test
• Test for acute HIV
infection
• Determine if women are
pregnant, planning
pregnancy, or
breastfeeding
• Confirm person is at
ongoing high risk
• If partner is poz,
determine if on
treatment
• Screen/vaccinate for hep
B
• Screen/treat STIs
• Don’t prescribe PrEP to
breastfeeding women
• Tell women that safety
of PrEP while pregnant
not fully assessed, but
no harm reported
Starting PrEP Regimen
• Prescribe one Truvada
tablet daily
• Prescribe no more that
90-day supply,
renewable only after
confirmed HIV-. Ensure
negative pregnancy test.
If pregnant, confirm
woman understands
about PrEP use during
pregnancy
• If hep B+, consider
Truvada for treatment
and HIV PrEP
• Provide risk reduction,
PrEP adherence
counseling, and
condoms
Follow-Up While on PrEP
• Test for HIV antibody
every 2-3 months
• Conduct pregnancy test
for women at each
follow-up visit; if
pregnant, discuss
continued PrEP use with
patient and prenatal
care provider
• Evaluate and support
PrEP adherence at each
visit, or more often if
needed
• Assess risk behaviors
and provide condoms
and counseling every 2-
3 months. Test for STIs
and treat, if present
Stopping PrEP
• Test for HIV to confirm
status
• If poz, test for resistance
and link to care
• If neg, link to risk
reduction services
• If hep B active when
PrEP started, consider
ongoing treatment
• If pregnant, tell prenatal
care provider of PrEP
use in early pregnancy
and coordinate care to
prevention MTC
transmission
29

30. 30

31. How did we get here? (Research!)
• All completed trials done on tenofovir & Truvada
• 3 trials = PrEP reduced risk of HIV infection
– i-PrEX (Truvada in gay men and trans women)
44% reduction overall (reported 2010)
Efficacy at 90% + with good adherence
– Partners PrEP (Truvada and tenofovir in het couples)
75% reduction Truvada (reported 2011)
– TDF2 (Truvada heterosexual men & women)
63% reduction overall (reported 2011)
31

32. How did we get here? (Research!)
• 2 trials = PrEP did not work
– FEM-PrEP (Truvada in women – stopped 2011)
– VOICE (Truvada, tenofovir – reported 2013)
• Both had very low adherence - though
self-reports were high)
• Low/undetected drug levels
• SOON - Bangkok Tenofovir Study (BTS)
– CDC study of injection drug users (2,400 +)
– Daily Tenofovir (75% chose directly-observed therapy)
– BTS results being reported in the
next couple of months
32

33. Home-grown Chicago PrEP research
• Project PrEPare
– Feasibility and acceptability trial of PrEP
– Enrolled 68 young gay/MSM
• ages 18-22
• 53% African-American, 40% Latino
– Randomized to Truvada, placebo, or no-pill
arm
– On study for 6 months
• very high retention (98.5%)
• self-reported adherence averaged 62% (range 43% - 83%);
detectable drug levels ranged from 63% - 20%
• unprotected sexual activity decreased
across all study arms
33

34. Home-grown Chicago PrEP research
• iPrEx OLE (open label extension)
– iPrEx randomized trial was diverse
worldwide, but not in the US
– Missing representation from
communities most affected
domestically
– Asked Chicago’s Project PrEPare
participants if they would like to join
iPrEx; 46 of 68 agreed
– Data coming!
34

35. Home-grown Chicago PrEP research
• Project PrEPare II
– Open label demonstration project AND
safety study of PrEP in young gay/MSM
ages 15-22
– Actively enrolling 300 youth in 13 US
sites, including Chicago
– Research questions:
1. How safe is PrEP use is among HIV-
uninfected young gay/MSM?
35

36. Home-grown Chicago PrEP research
• Project PrEPare II
2. What is acceptability, patterns of use, rates of
adherence and measured levels of drug exposure
when YMSM are provided PrEP and info re: safety
and efficacy of PrEP?
3. When YMSM are provided behavioral intervention
as well as PrEP and info re: the safety and efficacy of
PrEP, what are the patterns of risk?
4. Is implementing an efficacious group level or
brief individual level sexual risk reduction
intervention prior to provision of PrEP
acceptable and feasible?
36

37. Home-grown Chicago PrEP research
• Project PrEPare II
5. Is implementing a text messaging adherence
reminder intervention for youth whose adherence is
less than 80% acceptable, feasible?
6 . Are there demographic and/or behavioral
differences between youth who stay on PrEP
compared to those who discontinue?
7. Are there demographic and/or behavioral
differences between youth who interested in
participating in a PrEP study versus those who are
not?
37

38. Key research findings/Truvada
• Adherence! Adherence! Adherence!
• High adherence achieved 90%+ reduction in risk
• There appears to be a general “start-up
syndrome” w/Truvada that includes
nausea, diarrhea, abdominal pain and
headaches.
• Nausea most common (under 10%) and
resolved in 4 to 6 weeks
38

39. Key research findings/Truvada
• None of the Truvada PrEP trials to date have
shown increases in sexual risk behavior among
participants
• Across all PrEP studies of Truvada, there have
been no serious safety problems
• Very little drug resistance has been seen, only
among those with unidentified HIV infection
when they started the study
39

40. 40
The research continues

41. 41

42. 42

43. The research continues43

44. 44
Relative efficacy of TLC+, PrEP, other strategies
HPTN 052 (ARV treatment as prevention)1
Medical male circumcision1
STD treatment1
Partners PrEP (FTC/TDF) in discordant couples1
Subjects with detectable drug levels3
TDF2 (FTC/TDF) in men & women1
iPrEx (FTC/TDF) in MSM1
Subjects with detectable drug levels2
CAPRISA 004 (1% TFV vaginal gel) in
women1
FEM-PrEP (FTC/TDF) in women6, VOICE (FTC/TDF, TDF, TFV vaginal gel) in women7,
HIV vaccine (RV144)1
96%
75%
90%
62%
54%
94%
42%
39%
0 10 20 30 40 50 60 70 80 90 100
Efficacy (%)
Study
Reduction in HIV
Transmission
Not Significant
Condoms in heterosexuals4
Condoms in US MSM5
80%
70%
44%
1. Adapted from Abdool Karim S and QA. Lancet 2011;S0140-6736:1136-7
2. Amico R, et al. IAC 2012. Washington DC. #TUPE310
3. Baeten J, et al. NEJM 2012;367:399-410
4. Weller S, et al. Cochrane Database Syst Rev 2002:CD003255
5. Smith DK, et al. CROI 2013; Atlanta, GA. Oral #32
6. van Damme L, et al. NEJM 2012;367:411-422
7. Marrazzo JM, et al. CROI 2013; Atlanta, GA. Oral #26LB

45. 45
Condom Efficacy By Consistency of Use Among
Men Who Have Sex with Men (MSM) in the US
Condoms offer substantial but partial protection against HIV infection1
Reported sexual behavior and condom use
in 6-month interval
Receptive or Insertive Anal Intercourse
Efficacy
Always use vs. Never use 69.7 %
Sometime vs. Never use 4.4 %
1. Smith DK, et al. CROI 2013; Atlanta, GA. Oral #32
2. Weller S, et al. Cochrane Database Syst Rev 2002:CD003255
Analyzed efficacy of condoms in reducing HIV transmission in
HIV-uninfected MSM who had anal sex with at least 1 HIV-infected partner from 2 US
studies (N=3490): VaxGen 004 and Project Explore1

46. What PrEP does not do
• PrEP does not
– Guarantee a 100% protection from HIV (nothing does)
– Protect a person against other STIs like chlamydia,
syphilis, herpes, or gonorrhoea
– Prevent pregnancy
• Male and female condoms are still necessary to protect
against STIs and unplanned pregnancy
– Cure HIV
– Function as a treatment regimen for someone already
living with HIV
46

47. Why PrEP does not work for treatment
• People with HIV require taking
at least three ARVs together
• The two drugs in Truvada are
not sufficient to control the
virus
• A HIV+ person taking Truvada
on its own runs the risk of
developing resistance to the
drug, which will limit drugs
s/he can take for treatment
47

48. CDC – Clinical Practice Guidelines
• For clinicians – not “all purpose”
• Being drafted – expect to publish second half 2013
– Now – peer review, public engagement draft guidelines
– Next step to HHS for approval – then publish
• Includes info on evidence, guidelines for screening,
providing PrEP to gay men and heterosexuals,
discontinuing PrEP, clinical considerations, improving
adherence, reducing risk behaviors, info on financial case
management, fact sheets, risk index, counseling info, and
quality measures
48

49. Taking PrEP – what does it take?
• Adherence! Taking the pill every day.
• Honest, open, and on-going discussions with a
medical provider about sexual activity, HIV risk
• HIV antibody test – before first prescription, before
each prescription renewal
• Hepatitis B testing
• Kidney function
• STI screening
• Pregnancy testing
• Doctor visits approx. every 3 mos
to conduct all the above
49

50. Who should take PrEP?
• Person indicates interest in taking PrEP
• Why would someone want to take PrEP?
• Person is HIV-negative and has HIV+ partner
50

51. Who might be a good fit for PrEP?
• Sexual activity within high prevalence area or social
network, and/or:
– Doesn’t use male or female condoms consistently
– Diagnosed with STI(s)
– Exchanges sex for money, food, shelter, drugs, etc.
– Uses illicit drugs or depends on alcohol
– Is or has been incarcerated
– Does not know partner’s HIV status and one of the above
factors is true for partner
51

52. What about…
52

54. And about condoms…
54

55. And about condoms…
• Male and female (insertive) condoms are two of the most
effective ways to reduce sexual transmission of HIV, STIs,
and unintended pregnancy
• FDA’s indication advises use of condoms while on PrEP
– Results from PrEP clinical trials reflect condom promotion,
and increased use based on self-report
– PrEP doesn’t protect against STIs or pregnancy
• However, PrEP on its own is an option for individuals
who are not always able to use condoms
55

56. Is PrEP cost-effective?
• Modeling studies show the following factors to impact the cost-
effectiveness of PrEP:1-13
– Medication cost and availability of insurance coverage
– Targeted use among men and women at high risk
– Efficacy
– Changes in risk behavior
• Several analyses show PrEP to be cost-effective, particularly
when targeted to individuals at high risk of HIV acquisition2-5
1. Smith D. National Prevention Conference 2011. Atlanta. #E04
2. Juusola JL, et al. Ann Intern Med 2012;156:541-550
3. Desai K, et al. AIDS 2008;22:1829-1839
4. Walensky R, et al. CID 2012;epub April 3
5. Anderson J, et al. EACS 2009. Cologne.
6. Buchbunder S, et al. CROI 2012. Seattle. #1066
7. Grant R, et al. IAC 2006. Toronto. #THLB0102
8. Supervie V, et al. PNAS 2010;107:12381–12386
9. Paltiel DA, et al. Clin Infect Diseases 2009;48:806-15
10. Hill A, et al. CROI 2006. Denver. #Y-127
11. Hallett T, et al. CROI 2011. Boston. #99LB
12. Pretorius C, et al. PLoS ONE 2010;5:e13646
13. Abbas U, et al. PLoS ONE 2007;2:e875
56

57. Advantages
• Minimal side effects
• Convenience
• Effectiveness
Disadvantages
• Resistance
• Behavioral
Cost
• PrEP estimated $14,400/yr (varies by source and
attendant services)
• Annual cost of ARV for POZ = $24,000 +/-
• Intervention not forever
CDPH
2011
Policy
Analysis
57

58. 58

59. Accessing PrEP— from your doctor
• Any doctor who can write a
prescription can write one for
Truvada as PrEP
• Most HIV docs are familiar
with PrEP
• CORE, John Stroger
Hospital, TPAN does
referrals, etc.
• Bring along a fact sheet if you
think your doctor may need
some PrEP ed!
59

60. Accessing PrEP—insurance
FDA approval of
Truvada enables
private ins to cover
Truvada
on
Medicaid
formulary
Some ins
companies, states
have not yet decided
to cover
ADAP
does not
cover PrEP
60

61. Accessing PrEP – Gilead
1. Visit
www.truvada.com
2. Click on the link to
access information
about Truvada for a
PrEP indication
61

62. Alternatively, you can visit
www.start.truvada.com
Accessing PrEP
62

63. • Free male and female condoms are available
through www.Truvada.com
Male and female condoms
63

64. Medication assistance
• Gilead will provide Truvada for PrEP at no cost for
individuals who qualify for the assistance program
Program
Element
Truvada PrEP Medication Assistance Program
Eligibility
Criteria
US resident, uninsured or no drug coverage, HIV-
negative, low income (200% FPL)
Drug
Fulfillment
Product dispensed by Covance Specialty
Pharmacy, labeled for individual patient use and
shipped to prescriber (30 day supply); no card or
voucher option
Recertification
Period
6 months, with 90 day status check
6464

65. Medication assistance form
65

66. • Uninsured, financial need
• Available through www.Truvada.com
• Prescribers must first complete an online
assessment of the REMS materials, and then
may register to offer free testing
Free HIV/HBV testing
66

67. Hepatitis B and PrEP
• The drugs in Truvada treat Hep B
• A person considering PrEP must be tested for Hep B
before starting PrEP
• If person is negative, he/she should get the Hep B
vaccine
• People with Hep B may still be able to take Truvada for
PrEP
– This decision must be made with the advice of clinician
– Any decision to stop should be done in conjunction with a
medical provider
67

68. www.Truvada.com – Providers
• Allows providers to:
– Access to free condoms
– Obtain lab forms for free HIV-1 and HBV testing provided
that HCP has completed the online training and registered
– Gilead Medical Affairs Contact Number for subsidized testing
for individuals who seroconvert
– Receive similar training on the indication to the REMS
website
– Access to Gilead’s Medication Assistance Program for
download
– Access to all REMS materials for download
68

69. www.Truvada.com – HIV neg people
• Allows HIV-1 uninfected individuals to:
– Common questions, safety information
– Access to free condoms
– Opt-in for reminder service regarding regular testing for HIV-1
and other STDs (coming soon)
69

70. Helping your clients
understand PrEP
70

71. Messages to emphasize to clients
• PrEP is an OPTION
– Not forever, but maybe for a “season”
• Person must test HIV-negative to initiate
and continue PrEP.
• Daily adherence to PrEP is essential to
reduce person’s risk of HIV – and can be
very effective.
• Taking PrEP does not guarantee 100%
protection from HIV (but does anything?)
71

72. Messages to emphasize to clients
• Daily use of Truvada prescription of PrEP
cannot and does not function as HIV
treatment.
• PrEP user must be engaged with regular
health care for prescription, to ensure
remaining negative, staying adherent,
kidney health, etc.
• PrEP doesn’t make male or female
condoms obsolete!
72

73. Tips for talking about PrEP
• Important you feel
comfortable and confident
talking about PrEP.
• It’s okay to not have all of
the answers and to refer
your client to additional
resources and/or promise
to have that information
next time you see him/her.
73

74. Tips for talking about PrEP
• As a provider of prevention services, you are
viewed as a trusted source of information.
• Remember any perspectives/opinions you have
about PrEP and/or people who use PrEP will
translate to your clients.
74

75. 75
“It is frustrating to hear experts say that
prescribing Truvada to someone could
give them an unrealistic sense of safety
from becoming HIV+. I'm sure that's
true for some...but judging from my
own REAL (not hypothetical)
experience, it makes me more aware of
the risks I'm taking. I am reminded of
those risks on a daily basis, every time I
open that bottle and swallow that blue
pill. I don't take them lightly. If I did, I
wouldn't go through the trouble of using
Truvada.”
– Woman with HIV+ partner who started PrEP
because they wanted to have a child

76. Adherence, Adherence, Adherence
• Adherence to PrEP regimen is critical
• PrEP works if you take it.
It doesn’t work if you don’t take it.
• Clients may need additional adherence support
• Strategies for adherence include:
– Take pill each day at same time
– What might other strategies be?
– Place pill bottle in visible place, same place
– Set cell phone alarms
76

77. • My PrEP Experience
www.myprepexperience.blogspot.com (training slides)
• RSP on FB https://www.facebook.com/ProjectRSP
• Project PrEPare www.projectprepare.net
• Truvada as PrEP www.Truvada.com
• Project Inform www.projectinform.org/prep
• AVAC www.avac.org
– Thanks to AVAC for several slides
Web resources on PrEP
77

78. Onward RSP!
• What will you do with the info you learned today?
• How will you educate your clients about PrEP?
– Your colleagues? Your friends?
• Future training?
78

79. Please stay in touch
• Sybil Hosek
sybilhosek@gmail.com
• Staci Bush
Staci.Bush@gilead.com
• Jessica Terlikowski
jterlikowski@aidschicago.org
• Jim Pickett
jpickett@aidschicago.org
• Project RSP!
myprepexperience@gmail.com
79

80. Thank you!!
80