PEP/PrEP Flashcards
iPrEx study
- Phase 3 blinded, RCT, 2499 MSM + trans women
- Randomised to Truvada or placebo
- In those with detectable Truvada levels, 92% reduction in incidence of HIV
- In iPrEX-OLE no seroconversions seen when drug levels compatible with taking 4 or more pills a week
PROUD
- Phase 3, open label, randomised to receive daily dose Truvada immediately or after a deferral of 12 months
- At interim review it was recommended everyone get the trial drug as 20 in the deferred group Vs 2 in trial group had tested positive
IPERGAY
- Phase 3, double blind RCT in 414 mSM
- TVD on demand or placebo
- Regimen was double dose 2-24 hours before sex, daily dosing during period of sexual risk and then for 48 hours (2 doses) after
- 14 in placebo Vs 2 in treatment group tested pos
- Relative risk reduction 86%
DPMA and PrEP
- DPMA increasing risk of getting HIV
- PrEP largely overcomes this risk
- However, if a woman is at increased risk of HIV, ideally not using DMPA
Partners PREP
- Double blind placebo controlled RCT heterosexual couples Uganda + Kenya
- TDF vs TDF-FTC vs placebo
- Efficacy of TDF alone was 67% compared to placebo, and comparable to Truvada (75%)
- Therefore can give TDF alone in heterosexuals where FTC contraindicated
Baseline assessment and testing for PrEP
- HIV test (POC and 4th gen)
- Renal and UPCR
- Hepatitis screen
- STI screen
Indication of PEP following sub-optimal PrEP
- If risk through anal sex and at least 3 tablets taken in the last 7 days can restart with single dose of TVD (as will fulfil IPREX 4 doses/week)
- If fewer than 3 doses in last 7 days -> PEP
- In vaginal sex, consider PEP if more than 48 hours since last dose or fewer than 6 tablets in previous 7 days
- Short and long term side effects of PrEP
- Nausea/bloating/abdo pain/dizziness/headache usually short-lived, disappear in first month, can manage with simple analgesia or antiemetics
- Longer term bone and renal
Routinely offer PEP in the following scenarios
- Receptive anal sex (unless known and VL<20)
- Insertive anal sex (unless known and VL<20)
- Receptive vaginal sex where index HIV positive with unknown or detectable VL (consider if insertive)
- Not recommended in any situation for fellatio/splash semen/cunnilingus
- Occupational/other recommended if known HIV and VL unknown or detectable and sharps/mucosal splash, otherwise not recommended
Hep C final testing window
- Could do RNA 2 weeks post exposure if high risk
- Final testing hep C core antigen or RNA at 12 weeks or HEP C antibody at 6 months
When to discontinue due to missed doses of PEP
If more than 48 hours since last dose then discontinue
How effective is PEP?
- No RCT as not ethical
- Only been 1 case of HIV transmission in HCW when PEP has been used (the index case was highly treatment experienced)
- Sexual exposure no great evidence, one observational study in Brazil MSM saw 1 seroconversion in group taking PEP Vs 10 in group not taking
Risk of HIV transmission equation
Risk of getting HIV = risk source has HIV and has detectable VL x risk transmission per exposure
Risk of HIV transmission per exposure from an HIV positive individual who in NOT on suppressive ART
Receptive anal intercourse: 1 in 90
Receptive anal intercourse with ejaculation: 1 in 65
Receptive anal intercourse without ejaculation: 1 in 170
Insertive anal intercourse not circumcised: 1 in 161
Insertive anal intercourse circumcised: 1 in 909
Receptive vaginal intercourse: 1 in 1000
Needlestick: 1 in 333
Sharing needles: 1 in 149
Mucocutaneous: 1 in 1000
Semen splash to eye, oral sex <1 in 10,000
Hepatitis B transmission prevention if unvaccinated and higher risk source (PWID, MSM, high prevalence country)
(If HbsAb<10 at time of exposure then rapid course vaccination)
- Ultra rapid Hep B vaccination (0, 7, 21 days and 12 months)
- If source known HBsAg+ HBIG
- Check HBsAg and HBsAb at 12 weeks post exposure, if Abs<10 give booster
HIV1 and HIV2 are related to which animals viruses?
HIV1: simian immunodeficiency virus (SIV) in chimpanzees
HIV2: an SIV in sooty mangabeys
Diagnosis of HIV 2 window period
- p24 antigen testing is specific for HIV 1 only, therefore if using a 4th generation where there is risk of HIV2, it is essentially working as a 3rd generation and window period is 90 days
If you have indeterminate serology and HIV 2 RNA not detected (best test is ROCHE qualitative RT-PCR) then what is the next test to do?
- Proviral DNA (need to send to lab quickly, white cells are separated from whole blood and HIV 2 DNA that has integrated into human lymphocytes is looked for)
- Western blot diagnostics are not performed in UK
Diagnosis of HIV 2
- Need 3x CE marked tests
- First 2 CE marked 4th gen tests for HIV 1 and 2 followed by CE marked antibody only test
(If someone with a diagnosis of HIV 1 has an undetectable HIV VL and falling CD4, consider repeating HIV 2 serology and molecular tests in order to detect possibility of dual infection)
What to do if indeterminate HIV 1 or HIV 2 serology
Investigate with HIV 2 proviral DNA
When to start ART in HIV 2
- It is suggested that all start
- It is recommended where there is dual infection, primary infection, HBV, pregnancy, detectable viraemia, CD4<500, advanced HIV, OI or symptoms
What to start ART with in HIV2
- 2 NRTIs plus a second generation INSTI )BD DTG) or darunavir/ritonavir
- Generally give BD DTG or BD DAR/rit (unless consistently aviraemic)
- TDF or TAF/FTC is preferred backbone
- No NNRTIs due to intrinsic resistance, 2 drug regimens not recommended
Monitoring in HIV2, on and off treatment:
Off treatment: CD4 3-6 monthly (could be 6 monthly if CD4>500) and VL 6 monthly
On treatment: CD4 1, 3 and 6 months after starting and then 3-6 monthly depending on nadir CD4, if pre-treatment VL was detectable then VL at 1 month then 6 monthly
Risk of mother to child transmission without ART in HIV1 and HIV2
HIV1 25-30%
HIV2 0.6-4%
Neonatal PEP in HIV2
- Low or very low risk: 2 or 4 weeks zidovudine as per HIV1
- High risk should receive zidovudine/lamivudine/raltegravir
ART considerations in women conceiving on ART
- Generally don’t change
- Raltegravir must be 400mg BD
- No cobi
- If DTG give high dose 5mg folic acid
- No PI mono therapy
When to start ART in pregnancy?
- If VL<30,000 then as soon as able to do so in 2nd trimester
- If VL 30,000-100,000 then at start of 2nd trimester
- If VL>100,000 OR cd4<200 then as soon as possible even if first trimester
- (all should have started by 24 weeks)
What ART to start in pregnancy?
- Recommended to start with TDF or ABC with 3TC or FTC, then either EFV or ATZ
- Rilpivirine 25mg OD, RAL 400mg BD or DAR/r 600/100mg are alternatives (and this could be BD especially if any resistance), DTG 50mg if after 6 weeks
- TAF after 1st trimester
- Pick something INSTI based if baseline VL>100,000 or ART failing to suppress (similarly if late presenting and VL unknown)
- In HIV2 boosted PI based regimen such as BD darunavir/r is recommended
Management of untreated woman in labour
- Stat NVP 200mg
- Commence lamivudine 150mg BD
- Zidovudine 300mg OD
- Raltegravir 400mg BD
- Commence zidovudine infusion (2mg/kg/hr loading then 1mg/kg/hr until cord clamped)
- If pre-term labour give double dose TDF to load infant
- If delivery not imminent, consider CS
What to do if woman is Hep A non immune and has been diagnosed with hepatitis B in pregnancy?
Wait until after 1st trimester and then vaccinate against hepatitis A
- 0 and 6 months if CD4>300
- 0, 1 and 6 months if CD4<300
ART and testing considerations if diagnosed with HIV and Hepatitis B in pregnancy
- Ensure TDF or TAF (can have TAF after 1st trimester)
- Ideally FTC as shown to have slightly better anti-viral efficacy to 3TC but either ok
- Can omit FTC/3TC if clinical or genotypical evidence of resistant HBV (and do not use these drugs as the sole anti HBV drug)
- Test for Hep A, C and delta
HBV DNA, e antigen status as well as ALT/AST, Alb, INR, chronic liver disease screen and tests to determine hepatitis inflammation/fibrosis
Neonatal hepatitis B transmission prevention:
- Mode of delivery makes no difference, breastfeeding makes no difference
- All babies must be given HBV immunisation within 24 hours of delivery then follow normal infant vaccine schedule
- Give HBIG if:
-> Maternal HBV DNA>10 log 6
-> And/or woman is HBeAg positive
-> Woman Anti-HBe negative or unknown
Rate of VT of hep B if HbsAg and HbeAg positive?
70-90%
Rate of VT of hep B if HbsAg pos and HbeAg neg?
10-40%
Risk of VT of Hepatitis C and how to prevent it
- Risk is around 5% in mono infection, probably higher with HIV co-infection and if HCV viraemic
- Nothing can do to prevent it
- Ensure vaccinated against hep B and A
Recommendations for invasive antenatal testing if VL is detectable
- Start ART including raltegravir
- Stat dose NVP 2-4 hours before procedure
- Don’t do EVC if detectable
Recommended mode of delivery depending on HIV VL
- Make a decision with the 36 week VL
- VL<50 any mode of delivery supported
- VL 50-399: pre-labour CS at week 38-39 should be considered
- VL>400 PLCS recommended week 38-39
Management of spontaneous rupture of membranes
- VL<50: immediately start induction aiming for birth within 24 hours
- VL 50-399: recommend immediate CS although take other factors into account
- VL>400: immediate CS
When to use intrapartum IV zidovudine
- VL>1000 presenting in labour or with SROM admitted to PLCS
- Consider where VL 50-1000
- Untreated women (as well as the other meds)
Who is very low risk for VT
(2 weeks zidovudine mono therapy)
If all 3 of the following:
- On ART for longer than 10 weeks
- 36 week VL<50
- Two documented HIV VL<50 during pregnancy at least 4 weeks apart
Low risk for VT
(4 weeks zidovudine mono therapy)
- Criteria for very low risk are not all fulfilled but HIV VL at 36 weeks <50
- Infant born prematurely <34 weeks but most recent maternal HIV VL<50
Neonatal prep when high risk for VT (HIV VL known to be>50 on day or birth, uncertainty about maternal adherence of VL not known)
- 2 weeks Nevirapine
- 4 weeks zidovudine and lamivudine
- start as soon as possible and within 4 hours
(HIV 2 then zidovudine, lamivudine and raltegravir)
If not breastfed, how long postpartum will a HIV RNA/DNA detect 100% infections?
- 3 months
- HIV RNA or DNA similar sensitivities
- RNA requires 1 ml of blood, DNA can be done on less
- DNA is better as may get false neg RNA if maternal ART with agents that cross the placenta, but not always available, if RNA detected confirm with DNA
- Always get maternal sample same time to ensure the primers being used can detect the type of HIV
- If cannot amplify the maternal DNA despite 4 different primer sets then the 18 month antibody test is particularly important
Non breastfed testing:
- During first 48 hours and prior to discharge
- (2 weeks if high risk delivery)
- 6 weeks
- 12 weeks
- 22-24 month antibody test (engagement in care should continue until at least 18 months)
Breastfed baby testing
- During the first 48 hours and prior to discharge
- At 2 weeks
- Monthly for duration of breastfeeding
- At 4 and 8 weeks after cessation of breastfeeding
Preterm SROM management
- Management of preterm SROM at >34 weeks is same as above except that those 34-37 weeks will require group B strep prophylaxis in line with national guidelines
- When premature SROM occurs <34 weeks:
o IM steroids
o Optimise HIV VL
o MDR discussion about timing and mode of delivery
