1. PrEP Case Studies
Module 6

2. Summary recommendations…
Oral PrEP containing TDF should be offered to HIV-negative individuals at substantial ongoing risk of HIV infection
May be offered to HIV-negative partner in a serodiscordant relationship during attempts to conceive
Recommended regimen: TDF 300 mg + FTC 200 mg once daily (as a FDC)
PrEP does not eliminate risk of HIV infection, does not prevent STIs or unintended pregnancies
PrEP should only be offered after thorough assessment to establish eligibility, readiness for effective use, required follow-up, and absence of contraindications to TDF and/or FTC

3. Meet Des 40 year old truck driver Single
No past medical history of note
Sexual history
About 5 partners per month
Sex with female sex workers at truck stops
Uncomfortable when asked if he has sex with men
Condom use about “half the time”
No prior STI diagnosis
No regular GP

4. Des Symptoms On examination Think about…
Complains of severe fatigue for over one month
Two weeks of jaundice and itch
On examination
Jaundiced, not pale, not acutely unwell
No signs of chronic liver disease
Think about…
What is your differential diagnosis?
What tests would you perform?

5. The cause of his jaundice could be…
Hepatitis B infection
Hepatitis C infection
Alcoholic liver disease
All of the above

6. The cause of his jaundice could be…
Hepatitis B infection
Hepatitis C infection
Alcoholic liver disease
All of the above

7. Which tests would you do on Des?
Hepatitis serology
Liver function tests
HIV test
All of the above

8. Which tests would you do on Des?
Hepatitis serology
Liver function tests
HIV test
All of the above

9. Des: Results Liver Function Test Result Total bilirubin 58
Conjugated bilirubin 29
ALP
216
ALT
1429
AST
1706
Test
Results
Hepatitis A IgM and IgG
Negative
Hepatitis B surface antigen
Positive
Hepatitis B surface antibody
Hepatitis B E-antigen
Rapid syphilis
HIV (rapid)

10. Des: Follow up Referred to tertiary hospital liver clinic
Conservative management of viral hepatitis
Clinically well
LFTs remained elevated (ALT 42, AST 45)
Des asks about PrEP

11. Does Des need PrEP? Yes No
STI screen – State sector this means clinical assessment for an STI syndrome and also rapid syphilis. Insufficient. Consider PCR screening

12. Does Des need PrEP?
Yes - substantial ongoing risk, inconsistent condom use No
STI screen – State sector this means clinical assessment for an STI syndrome and also rapid syphilis. Insufficient. Consider PCR screening

13. To assess eligibility for PrEP, what do you check?
Creatinine clearance
HIV status
Readiness to adhere to PrEP
All of the above?

14. To assess eligibility for PrEP, what do you check?
Creatinine clearance
HIV status
Readiness to adhere to PrEP
All of the above?

15. Would you prescribe PrEP for Des?
Yes No

16. Would you prescribe PrEP for Des?
Yes - two indications for TDF/FTC; transmission risk in light of inconsistent condom use No

17. The Safety of PrEP in the Presence of Hepatitis B Infection
Most studies to date excluded HBV-positive individuals
Concern about “flares” if stop TDF/FTC
HBV is common in countries that don’t vaccinate
20% of incident infections become chronic
TDF/FTC suppresses HBV and thus acts as treatment

18. The Safety of PrEP in the Presence of Hepatitis B Infection
Substudy of HBV-positive participants in iPrEx
13/2499 (0.5%) chronic HBV
6 were in the group assigned TDF/FTC
0/6 experienced “flares” after stopping PrEP
2 participants had evidence of acute HBV and started PrEP  severe elevated LFTs (as expected in acute infection) which settled and both cleared virus and became immune

19. Back to Des… You treat his syphilis
Repeat HIV test (fourth generation rapid) is negative, as was one two weeks previously
Currently well, no symptoms of acute illness
Creatinine clearance > 60 mL/min
Liver functions are slightly elevated
Liver ultrasound normal

20. Des: Outcome You prescribe PrEP for Des
Hepatitis B viral load now undetectable
Liver function tests completely normal
Normal renal function
Good pill taking
Remains HIV-negative

21. One year later… One year later, Des has been diagnosed as diabetic
Steadily declining renal function, with proteinuria and creatinine clearance now 47 mL/min
He has remained HIV-negative, but has presented with a number of STIs

22. What now? Several issues:
From risk perspective, Des remains a candidate for PrEP (STIs)
BUT
Dual indication for TDF/FTC
Risk of HBV flare if stop PrEP (risk is unquantified)
Stop TDF/FTC with careful monitoring of LFTs
Other risk reduction strategies and prevention measures

23. Meet Anna 27 years old Previously well, no medical history of note
Recently married
Discordant couple
Husband, Joe, CD4 count is 1000 cells/mm3
She has been using condoms but her husband is not happy to continue using them

24. What HIV prevention strategies are least suitable to this couple?
Condoms and lubricants alone
PEP
PrEP as part of combination prevention
TasP

25. What HIV prevention strategies are least suitable to this couple?
Condoms and lubricants alone
PEP
PrEP as part of combination prevention
TasP

26. Anna: Follow Up
Key counseling points?

27. Anna: Follow Up Husband Anna comes to see you one month later
Advise treatment and link to care at nearest ART facility
Promote condom use
Discuss that he should wait until he is virally suppressed before planning a family
Anna comes to see you one month later
Husband has not yet attended for ART
Requests PrEP (she heard about PrEP from a friend)

28. Does Anna need PrEP?
Yes No

29. Does Anna need PrEP?
Yes - ongoing exposure (husband doesn’t like condoms and not yet on ART) No

30. What results do you need to exclude contra-indications to TDF?
Creatinine clearance > 60 mL/min
Negative HIV test
Negative pregnancy test
All of the above

31. What results do you need to exclude contra-indications to TDF?
Creatinine clearance > 60 mL/min
Negative HIV test
Negative pregnancy test
All of the above

32. Anna’s Results… HIV-negative Creatinine clearance 104 mL/min
HBsAg and STI screen negative
Pregnancy test negative – you advise contraception

33. Anna’s Follow Up All well at months 1, 3, and 6 Correct pill taking
Using condoms about 50% of the time
Started taking oral contraceptives
Husband started ART four weeks previously

34. USS scan confirms viable 20 week male foetus
Anna’s Follow Up
All well at months 1, 3, and 6
Correct pill taking
Using condoms about 50% of the time
Started taking oral contraceptives
Husband started ART four weeks previously
USS scan confirms viable 20 week male foetus

35. What now – would you stop PrEP?
Continue PrEP
Mother
Ongoing HIV risk to mom
(5% incidence in some studies)
Protects mom
Baby
Minimises risk to baby
Risk of bone abnormalities but insufficient data
“There are no adequate and well-controlled studies of TDF/FTC for PrEP in pregnant women”
“Pregnancy and breastfeeding are not contraindications to provision of PrEP. Pregnant or breastfeeding women whose sex partners are HIV-positive or are at high risk of HIV infection may benefit from PrEP as part of combination prevention of HIV infection”

36. What now – would you stop PrEP?
Continue PrEP
Mother
Ongoing HIV risk to mom
(5% incidence in some studies)
Protects mom
Baby
Minimises risk to baby
Risk of bone abnormalities but insufficient data
In SA TDF/FTC is contra-indicated for PrEP use during pregnancy/breastfeeding
Tenofovir is FDA category B risk in pregnancy
Lots of experience of use in pregnant HIV-positive mothers
Case by case decision based on risks and benefits
“There are no adequate and well-controlled studies of TDF/FTC for PrEP in pregnant women”
“Pregnancy and breastfeeding are not contraindications to provision of PrEP. Pregnant or breastfeeding women whose sex partners are HIV-positive or are at high risk of HIV infection may benefit from PrEP as part of combination prevention of HIV infection”
[Insert country specific information]

37. Anna: Outcome Elected to stop PrEP
Husband agreed to use condoms consistently as long as not permanent
 Successful normal delivery
 Baby (and Anna) remain HIV-negative
 Husband now on ART and VL LDL

38. Meet George 42 year old single gay man
First contact with clinic in Nov 2011
Unprotected sex 60 hours previously
Received PEP
Remained HIV-negative
Repeat exposures requiring PEP in 2013, 2014 and 2015
Primary sex partner is HIV-positive on ART
Enquired about PrEP in July 2015

39. Is George a good candidate for PrEP?
Yes No

40. Is George a good candidate for PrEP?
Yes - ongoing risk exposure No

41. You assess George to see if he is eligible for PrEP
What tests do you do?

42. You assess George to see if he is eligible for PrEP
HIV test (fourth generation) negative previously and at this visit
Sexual history: last exposure about 10 days ago
Clinical assessment: current URTI (presumably viral)
Creatinine
HBsAg

43. George’s Results HIV rapid test negative Creatinine 98 umol/L
Creatinine clearance > 60 mL/min
HBsAg-negative
HBsAb-positive

44. Do you start PrEP?
Yes No

45. Do you start PrEP? Yes No - recent exposure and clinical presentation
Delay PrEP and review in 2-4 weeks
Counselling / condoms / lubricant
Two weeks later: HIV-negative and clinically well
Start PrEP

46. One month follow up… Correct pill taking confirmed No current STIs
Ongoing potential HIV exposures
Side effects settled after 5 days
What tests are required?
STI screening at one month is not included in the guidelines but will depend on reported sexual activity and exposure.

47. One month follow up… Creatinine 117 Cr Cl 56
Correct pill taking confirmed
No current STIs
Ongoing potential HIV exposures
Side effects settled after 5 days
What tests are required?
STI screening at one month is not included in the guidelines but will depend on reported sexual activity and exposure.
STI screen – State sector this means clinical assessment for an STI syndrome and also rapid syphilis. Insufficient. Consider PCR screening
Creatinine 117
Cr Cl 56
Confirmation of HIV-negative status
STI screening (depending on reported sexual activity)
Repeat creatinine and creatinine clearance

48. Ongoing Management PrEP stopped, BUT: Client is a doctor!
Counselled about risks and benefits
Ongoing high risk of HIV exposure
Unwilling to increase condom use
Social event with excess alcohol the day before monitoring occurred
 Chooses not to stop but to increase monitoring

49. Ongoing Management Looked for alternative causes of renal dysfunction
Not hypertensive
Normal random glucose
Total fasted cholesterol 5.3
No nephrotoxic agents (e.g. no NSAIDs)
No family history
Normal urine dipstix (no proteinuria)
Continue PrEP
Repeat renal function:
Creatinine 103
Cr Cl > 60

50. Three months later… Creatinine 135 Cr Cl 48
Correct pill taking confirmed
No current STIs
Repeat creatinine
Scripted 3 months of PrEP
Stop PrEP
Counselling/advice about HIV prevention
Creatinine 135
Cr Cl 48

51. Outcome Patient does not want to stop PrEP
Elected to continue despite medical advice with close monitoring
Renal function has improved slightly and stabilised (Cr Cl approx 55 mL/min)
Increasing comfort level that tenofovir-induced renal dysfunction may plateau
AGAINST current guidelines!

52. Mean Change in CrCL (mL/min)
Renal safety
Renal safety assessment of 2499 HIV-negative subjects in iPrEx study
Mean Change in CrCL (mL/min)
TVD
Placebo
P-value
Wk 4
-2.4
-1.1
0.02
At Stop
+0.3
+1.8
Post-stop
-0.1
0.0
0.83
A mild, non-progressive decrease in creatinine clearance (Cockcroft-Gault), that was reversible and readily managed with routine monitoring
Did not vary by race, age, or HTN history
Affected by NSAID use
-3.4 mL/min (+NSAID) vs mL/min (no NSAID), P = 0.04
Change in Creatinine Clearance from Baseline (mL/min)*
* in 1,137 subjects
Solomon M, et al. AIDS 2014

53. Decline in eGFR resolves within weeks of discontinuing TDF or FTC/TDF for PrEP
Partners PrEP: Phase 3, randomised trial of daily oral TDF PrEP vs. FTC/TDF PrEP vs. PBO among African HIV-negative men and women (N=4747) with normal baseline renal parameters
SCr was assessed quarterly while on study medication, and at 2 monthly visits after d/c
eGFR was calculated using CKD-EPIa
Mean eGFR was 2-3 mL/min lower on PrEP vs. PBO (P<0.01) at first post-study drug visit
>96% of participants had >75% eGFR reversion to baseline levels by 8 weeks of study drug discontinuation
Mean eGFR at the last on-study and first post-study drug visit
Last on-study drug visit
First post-study drug visita
Mean eGFR (mL/min/1.73m2)
TDF
FTC/TDF
Placebo n
1271
1308
1345
130
120
125
135
a Chronic Kidney Disease Epidemiology Collaboration Equation.
b Median time from the last on-study drug visit to the first post-study drug visit was 4 weeks (IQR: 3 - 5), which was similar across treatment groups.
Mugwanya, K. CROI 2015

54. Additional Case Studies

55. Case Study: Lebo Lebo is a 27 year old woman living in Hillbrow.
She comes into the clinic with complaints of an STI.
She works as a part-time domestic helper during the day and she also works at a bar some evenings.
She has two small children, and her husband has passed.
She is not on contraception as she does not like the side effects. She wants to take an HIV test and look at potential options for contraception with low side effects. She also wants a box of condoms, because after some conversation, she admits she has a couple of sexual partners.
Results:
Creatinine Clearance: 74
HBSAg Negative
HIV negative

56. Lebo
What are the steps you would undertake to further assess what Lebo might need in terms of contraception and HIV prevention?
What messages will you give her around risk and prevention of unwanted pregnancies, STIs, and HIV?
Do you think Lebo should consider PrEP as an HIV prevention option? Why or why not?
If you give her PrEP as an option, what will you tell her about taking the drug (e.g. side effects and adherence)?
Results:
Creatinine Clearance: 74
HBSAg Negative
HIV negative

57. Case Study: Candice Candice is an 18 year old transgender woman
Her parents have died
She engages in sex work to support her young brother.
She is worried about recurring STIs and has been to the clinic previously to start PrEP
She admits that she only started taking her PrEP after two weeks of getting the script filled and has not been very consistent in taking the pills every day
She has experienced some very minor side effects (upset stomach), and is unsure about continuing to take PrEP

58. Candice
Whose decision is it as to whether Candice should continue PrEP?
What messages will you give her around risk and adherence to PrEP?
How can you help her decide whether to continue PrEP and what strategies she could use?
What are the steps you would undertake to further assess what Candice should do in terms of preventing HIV and STIs?

59. Case Study: Jackie
Jackie is 15 and lives in an area where gangs and crime are rife.
She has been raped once, so have many of her friends.
Her mother brings her to the clinic to discuss the prevention against HIV and pregnancy.
She also suspects her daughter and her boyfriend are having sex, although Jackie denies it.
Her mother has heard about this PrEP pill and thinks this should be given to her daughter.

60. Jackie
What is your personal feeling about this? How would you handle this professionally?
Is Jackie eligible for PrEP?
What additional information do we need to confirm eligibility ?
What are her rights? What about her mother’s right to protect her?
What issues would you discuss with them?

61. Case Study: Lerato Lerato is a 16 year old adolescent
She is an orphan and has been brought up by her aunt, who sells alcohol as a means of income.
Lerato is sexually active and has a boyfriend
She also does favours for her aunt's clients so that they can keep coming back.
Her aunt is aware of that and advised Lerato to use an injection to prevent pregnancy.
Her aunt does not believe Lerato can contract HIV from her customers because they are high profile and respectable men.
Lerato is, on the other hand, thinking of making extra money for herself by doing transactional sex with some of the customers

62. Lerato Can Lerato be considered high risk for contracting HIV?
Would she be eligible for PrEP?
What prevention strategies can be recommended to Lerato other than PrEP?
What are the possible disadvantages of PrEP for girls aged 16?
Remember that the age of consensual sex in SA is 16 years. No social worker involvement here

63. References
Solomon MM, Lama JR, Glidden DV, Mulligan K, McMahan V, Liu AY, Guanira JV, Veloso VG, Mayer KH, Chariyalertsak S, Schechter M, Bekker LG, Kallás EG, Burns DN, Grant RM; iPrEx Study Team. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis. AIDS. 2014 Mar 27;28(6):851-9
Mugwanya, K. CROI 2015, Seattle, WA #981

64. Acknowledgements With thanks to:
The Southern African HIV Clinician Society (Michelle Moorhouse)
Wits Reproductive Health and HIV Institute (Robyn Eakle, Melanie Pleaner)
Anova Health Institute (Dr. Kevin Rebe, Ben Brown)
The Elton John AIDS Foundation
Health4Men
Right to Care