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1. FOURTH ANNUAL USC COLLEGE OF NURSING
CLINICAL PRACTICE CONFERENCE
S A B R A S . C U S T E R , D N P, M S , F N P - B C
C L I N I C A L A S S O C I AT E P R O F E S S O R , C O L L E G E O F N U R S I N G
P R E P S L I D E S O R I G I N A L LY B Y D I V YA A H U J A , M D
A S S O C I AT E P R O F E S S O R , S C H O O L O F M E D I C I N E
PrEP and PEP for HIV: Before and
After Prevention

2. Annual HIV Incidence
 There are approximately 50,000 new infections in the US
each year
 Homosexual men (MSMs), particularly young, African-
American MSMs are disproportionately affected
 African-Americans in general are disproportionately affected
http://www.cdc.gov/hiv/statistics/overview/ataglance.html

3. HIV Prevention Efforts
Abstain, Be faithful, Condoms,
Counseling & testing
ABC
C
Diaphragms
D
E
F
G
H
I
Exposure prophylaxis
(MTCT, PEP, PrEP)
Female-controlled
microbicides
Genital tract
infection control
HSV-2 suppressive
treatment
Immunization
Ramjee G. XVI IAC, Toronto 2006, #TUPL02
Circumcision

4. PRE-EXPOSURE PROPHYLAXIS
PrEP

5. June 2013
CDC Interim Guidance:
PrEP for IDU
PrEP Timeline
November 2010
iPrEx
January 2011
CDC Interim Guidance:
PrEP for MSM
August 2012
TDF2
Partners PrEP
August 2012
CDC Interim Guidance:
PrEP for
heterosexuals
July 2012
FEM-PrEP
June 2013
Bangkok TDF Study
July 2012
FDA Approval
TDF/FTC PrEP
May 2014
US Public Health Service
Clinical Practice
Guideline for PrEP
March 2013
VOICE

7. Barriers to Use of PrEP
 Eligibility
 Adherence
 Increased risky sexual practices
 Side effects
 Reimbursement
 Patient accountability
 Provider knowledge, comfort, and willingness to
prescribe

8. PrEP Candidates
 Men who have sex with men (MSM) who:
 Have an HIV-positive sexual partner
 Have a recent bacterial STI
 Have a high number of sex partners
 Have a history of inconsistent/no condom use
 Engage in commercial sex work
 Transgender individuals who:
 Engage in high-risk sexual behaviors
http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf

9. PrEP Candidates
 Heterosexual women and men who:
 Have an HIV-positive sexual partner
 Have a recent bacterial STI
 Have a high number of sex partners
 Have a history of inconsistent/no condom use
 Engage in commercial sex work
 Live in a high-prevalence area or network
 Injection drug users (IDU) who:
 Have an HIV-positive injecting partner
 Share injection equipment
 Have been through recent drug treatment (but currently
injecting)
http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf

10. iPrEx Study
 Randomized, controlled study
 High-risk (MSM) assigned to Truvada vs placebo
 44% reduction in the incidence of HIV
 Secondary analysis of individuals on PrEP
Acquisition reduced by 92% in those with
detectable drug levels
Grant RM, Lama JR, Anderson PL, et al; iPrEx Study Team. Preexposure
chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J
Med 2010;363(27):2587-99.

11. The PROUD Study
 The PROUD study enrolled MSMs from 13 sexual health
clinics in England between 2012 and 2014
 Eligibility criteria :
 negative HIV test
 condomless anal intercourse in the previous 90 days
 545 MSM randomized 1:1 to daily TDF/FTC
 Either immediately (IMM)
 Or after a deferral (DEF) period of 12 months
 Relative reduction in HIV acquisition of 86% in the
Immediate arm (62-96%; P=0.0002).
 Confirmed STI (rectal chlamydia/gonorrhea) in
 Immediate arm-29%
 Deferred arm -27%
McCormack S, Dunn D, Desai M. (2016) Pre-exposure prophylaxis to prevent the acquisition of HIV-1
infection (PROUD)… The Lancet 387(10013),53-60.

12. PrEP Studies:
HIV transmission risk lowest when participants took PrEP consistently
STUDY OVERALL
Reduction in risk of
HIV infection
Detectable level of
medication in the
blood
Reduction in risk of
HIV infection
iPrEx 44% >90%
TDF2 62% ---
Partners PrEP 75% 90%
PROUD 86%
BTS 49% 74%
Adapted from summary of research at http://www.cdc.gov/hiv/prevention/research/prep/

13. Rule out Acute HIV Infection before PrEP
Symptoms of Acute HIV
 Fever
 Fatigue
 Myalgia
 Skin rash
 Headache
 Pharyngitis
 Cervical Lymphadenopathy
 Arthralgia
 Night sweats
 Diarrhea
Daar ES, Pilcher CD, Hecht FM. Curr Opin HIV AIDS. 2008;3(1):10-15.

14. Case Study
32 year old black female seeks pregnancy.
Tested six months ago and is HIV-negative.
Her male partner is HIV-positive and not currently on
antiretroviral treatment.
What do you recommend?

15. PrEP for Safe Conception
 Mother takes PrEP to prevent her from acquiring
HIV from male partner
 Limited data
 In the small studies, no HIV transmission to the
woman
 Among women in Antiretroviral Pregnancy Registry:
no birth defects with Truvada

16. PrEP for Serodiscordant Partners
 54 year male
 Monogamous with HIV-positive partner
 The HIV positive partner has had a undetectable
viral load for > 1 year.
 Would you give PrEP to the HIV negative partner?

17.  CDC guidelines support PrEP even when the HIV
positive partner is undetectable
 Likelihood of acquiring HIV is very low from a
virally-suppressed HIV-positive partner
 However:
 Partner may have virological blips
 Partner may become non adherent
 Patient may not be monogamous

18. 2014 PrEP Prescribing Guidelines
 Determine eligibility: negative HIV test, high risk of
infection and creatinine clearance > 60ml/min
 Assess for Hepatitis B sAg and pregnancy (female
patients)
 Prescribe : Tenofovir-emtricitabine (Truvada) one
pill once daily (90 day supply)
 Monitor: creatinine clearance, HIV status, and
pregnancy every 3 months and STI screen every 6
months; counsel on adherence and risk reduction
http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf

19. Providing PrEP
Before starting PrEP:
 Clinical eligibility
 Educate
 Side effects
 Limitations
 Daily adherence
 Symptoms of seroconversion
 Monitoring schedule
 Safety
 Criteria for discontinuation
 Partner information
 Social history: housing, substance use, mental health, domestic
violence

20. Providing PrEP
After confirmation of clinical eligibility:
 Prescribe no more than 90-day supply of PrEP
 Truvada 1 tablet PO daily
(tenofovir 300mg + emtricitabine 200mg)
 Insurance prior approval
 Truvada for PrEP Medication Assistance Program

21. Providing PrEP
3-month visit:
 HIV test
 Assess for acute infection
 Check for side effects
 Pregnancy testing
 Prescribe 90-day supply of medication
Every visit:
Assess adherence
Risk reduction counseling
Provide condoms

22. Providing PrEP
6-month
 HIV test
 STI test
 Pregnancy test
 Renal function
 90 day prescription
9-month
 HIV test
 Pregnancy test
 90 day prescription
12-month
 HIV test
 STI tests
 Pregnancy test
 Renal function
 90 day prescription
 Assess the need to
continue PrEP
Every visit:
Assess adherence
Risk reduction counseling
Provide condoms

23. Discontinuing PrEP
 Positive HIV result
 Acute HIV signs or symptoms
 Non-adherence
 Renal disease
 Changed life situation: lower HIV risk
http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf

24. On-Demand PrEP
 IPERGAY:
 randomized trial, 400 high-risk MSM
 peri-coital PrEP:
Truvada 4 tablets or placebo two 2 to 24 hours before
sex, a second dose 24 hours later, and a last one 24 hours
later
 86% reduction in HIV acquisition with on-demand PrEP

25. Future of PrEP
 Nano-formulations or long acting meds
 Cabotegravir: investigational HIV integrase inhibitor
Can be administered orally or as long-acting
subcutaneous or intramuscular injection
Single injection of long-acting version could be effective
for up to 3 months

26. Financial Issues
 Coverage for PrEP varies in US
 Most private insurers are providing coverage, with
prior authorization requirements
 Potential issue of economic disparity for
uninsured/low-income patients

27. Reimbursement for PrEP
 Follow the CDC Clinical Guidelines for PrEP
 Common ICD-10 codes for PrEP counseling:
Z20.2 “Contact with and (suspected) exposure to
infections with a predominantly sexual mode of
transmission”
Z11.4 “Encounter for screening for HIV”
Z11.3 “Encounter for screening for infections with a
predominantly sexual mode of transmission”
 Use the usual E/M charge based on
length/complexity of visit

28. Reimbursement for PrEP
 Although regular HIV screening labs are rated “A” by
USPSTF and should be covered without a “patient
due balance”, the greater frequency of labs needed
while on PrEP may generate charges
 Broad coverage by Medicaid for PrEP – prior
authorizations may be necessary
-SC Medicaid does provide Truvada for PrEP with
NO prior authorization necessary
 Broad coverage for Truvada by private insurers as
well, prior authorizations also likely necessary

29. Truvada Costs
 Out-of-pocket estimated expense: $1,300 a month
 The manufacturer of Truvada offers assistance to
uninsured individuals:
http://www.gilead.com/responsibility/us-patient-
access/truvada%20for%20prep%20medication%20a
ssistance%20programstar
 The manufacturer of Truvada also has a co-pay
assistance program applicable to some insured
individuals: https://start.truvada.com/

30. Payment Assistance Information
 Project Inform:
http://www.projectinform.org/pdf/PrEP_Flow_Chart.pdf
-explains payment assistance for insured and un-
insured
 Assessment of Medicaid Coverage of HIV/AIDS
Prevention, Screening, and Care Services: A Ten
State Review:
https://careacttarget.org/sites/default/files/supporting-
files/Assessment%20of%20Medicaid%20Coverage.pdf

32. PrEP works.
Lets use it appropriately and responsibly

33. POST-EXPOSURE PROPHYLAXIS
PEP

34. PEP Categories
 oPEP –for occupational exposures
 HCWs who may experience a cut, needle stick, or
other potentially infectious body fluid exposure
“on the job”
 nPEP –for non-occupational exposures
 Persons who are potentially exposed to HIV
through consensual or forced intercourse,
accidental puncture wounds, or IVDU

35. Occupational HIV Exposures
 Definition of exposure: percutaneous injury or
contact of mucous membrane or non-intact skin
with blood, tissue, or other potentially infectious
body fluids
-potentially infectious body fluids: semen, vaginal
secretions, CSF, synovial fluid, pleural fluid,
peritoneal fluid, pericardial fluid, amniotic fluid
-only potentially infectious if visibly bloody: feces,
nasal secretions, saliva, sputum, sweat, tears, urine,
vomitus

36. Risk of Occupational HIV Transmission
 Average risk after percutaneous exposure to
HIV-infected blood: 0.3%
 Average risk after mucous membrane exposure to
HIV-infected blood: 0.09%
 Factors that increase risk of HIV transmission:
-device (needle, etc) is visibly contaminated with blood
-needle had been placed directly into a vein or artery
-deeper injuries
-amount of HIV present in the source patient’s blood

37. Non-Occupational HIV Exposures
 Sexual contact, consensual or forced
 Accidental cuts or punctures with sharp objects
 Intentional use of contaminated or shared needles
for IVDU

38. Evaluation of Non-Occupational Exposures
 HIV status of the potentially exposed person
-baseline rapid testing should be conducted to ensure they are not
already HIV-positive
 Timing and frequency of exposure
-nPEP should be initiated within 72 hours of exposure
 Risk of HIV acquisition based on type of exposure
 HIV status of the exposure source
-often difficult to obtain for non-occupational exposures

39. Risk of Non-Occupational HIV Transmission
 Receptive anal intercourse = 1.38%
 Receptive penile-vaginal intercourse = 0.08%
 Needle sharing for IVDU = 0.63%
 Needlesticks = 0.23%
 As with occupational exposures, increased amount of
HIV present in the source patient’s blood or body
fluids increases risk of transmission
 For sexual exposures, non-intact mucous
membranes increases risk of transmission

40. Other Considerations for Possible Sexual
Exposures
 Prophylaxis for bacterial STIs, trichomoniasis
 Testing for Hepatitis B and C
 Pregnancy prevention for female patients
 Counseling and other support for survivors of sexual
assault

41. Shared Principles for All Types of PEP
 Importance of quick initiation of PEP following
possible HIV exposure
 Importance of HIV tests for the potentially exposed
patient
 Use of a “complete” three-drug regimen for PEP
 Duration of treatment is 28 days
 Follow-up testing required at 6 weeks and 4 months
(with newest, 4th-generation Ag/Ab tests)

42. Time is of the Essence!
 PEP should be initiated as quickly as possible for all
types of exposures
 nPEP guidelines state effectiveness is unlikely >72
hours after exposure
 For frequent possible exposures, discuss PrEP with
the patient

43. Baseline Testing for Exposed Person
 Gold standard is the 4th generation Ag/Ab test to
establish that exposed person is currently
HIV-negative
-decreased window period compared to older tests
 Familiarity with common manifestations of acute
HIV infection could be helpful for rare instances of
very acute HIV exposed person
-can proceed based on 4th generation test results, but consult to ID
would be prudent

44. What to Prescribe?
 oPEP and nPEP guidelines recommend the same
regimen:
emtricitabine/tenofovir DF (Truvada)200/300 mg daily
+
raltegravir (Isentress) 400 mg twice daily
~For 28 days~

45. Alternative Choices
 Dolutegravir (Tivicay) 50 mg can be substituted for
raltegravir (Isentress), advantage is once-daily
dosing
 For renal dysfunction (creatinine clearance < 59
mL/min), can substitute zidovudine/lamivudine
300/150 (Combivir) or dose-adjust the individual
components
 nPEP guidelines include recommendations for
weight-adjustment for children

46. Additional Items
 Guidelines recommend checking serum creatinine at
4-6 weeks after exposure (along with first follow-up
HIV test) for patients prescribed Truvada
 Provision of ‘starter packs’ in the emergency
department setting is recommended for survivors of
sexual assault who need PEP
 Consider follow-up and broader support needs for
survivors of sexual assault

47. References
 US Public Health Service (2014). Preexposure Prophylaxis for the
Prevention of HIV Infection in the United States – 2014. Retrieved
from:
http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf
 Kuhar, D, et al (2013, Sept). Updated US Public Health Service
Guidelines for the Management of Occupational Exposures to
Human Immunodeficiency Virus and Recommendations for
Postexposure Prophylaxis. Infection Control and Hospital
Epidemiology, (34,9), pp.875-892
 CDC, US DHHS (2016). Updated Guidelines for Antiretroviral
Postexposure Prophylaxis After Sexual, Injection Drug Use, or
Other Nonoccupational Exposure to HIV – United States, 2016.
Retrieved from: https://stacks.cdc.gov/view/cdc/38856