Pre-Exposure Prophylaxis (PrEP) for HIV
/Reading:
ACOG June 2022 Practice Advisory on PrEP and ACOG CO 595 on PrEP
CDC on PrEP
Old episodes on HIV in Pregnancy and HIV and GYN Care
What is PrEP?
Pre-exposure prophylaxis specifically for prevention of HIV
Use of antiretroviral medication to individuals who do not have HIV, but are at risk for it.
Has been recommended by the CDC since 2012.
Why is PrEP needed?
HIV remains a significant public health problem in the USA and around the world.
1.2 million persons have HIV as of 2021, with 87% aware of their diagnosis.
About 36,000 people receive HIV diagnosis per year.
Heterosexual contact accounts for ~22% of all HIV diagnoses.
Injection drug use accounts for ~7% of diagnoses.
The majority of new infections occur during reproductive years – about 20k of the 36k diagnoses per year are under the age of 35.
Persons of color and trans persons are disproportionately affected – and PrEP can be part of solution to fight inequity.
PrEP is effective, but underutilized:
23% of persons who can benefit from PrEP are prescribed it – lots of room for improvement!
Discuss more on efficacy later.
As part of CDC’s End the HIV Epidemic initiative, they hope to increase PrEP coverage to 50% by 2025.
How effective is PrEP?
Very! Let’s quickly review some major trial data in heterosexual couples:
2012: TDF2 Study Group, NEJM
RCT in Botswana randomizing to daily tenofovir-emtricitabine or placebo.
Two reverse transcriptase inhibitors
Brand names: Truvada, Descovy
1219 men and women underwent randomization (45.7% women) and followed for a median of 1.1 years, but max 3.7 years.
9 persons in treatment group and 24 persons in the placebo group became infected.
Estimated efficacy: 62.2%.
Higher rates of nausea/vomiting and dizziness in treatment group, but not long enough following to determine long-term safety data.
2012: Partners PrEP Study Team, NEJM.
RCT in Kenya and Uganda for HIV-1 serodiscordant heterosexual couples, with three arms: daily tenofovir; daily combination tenofovir-emtricitabine; or placebo.
4747 couples were followed.
In 38% of couples, the seronegative partner was female.
17 infections in the tenofovir group; 13 infections in the combo drug group; and 52 infections in the placebo group.
Risk reduction of 67% with tenofovir alone, and 75% with the combo drug.
Rates of serious adverse events similar across groups.
2012: FEM-PrEP Study Group, NEJM
RCT in multiple countries in Africa
2120 HIV-negative women to tenofovir-emtricitabine or placebo daily over two years.
33 infections in combo drug group, 35 infections in placebo group.
No difference. Why?
Hypothesized that adherence was poor – while pill-count data suggested 88% of meds were taken, drug level testing suggested target plasma level was only identified in about 25% of participants tested.
Remember that a daily pill regimen can be challenging!
The CDC currently says that PrEP is:
99% effective in reducing risk of HIV acquisition from sexual activity
74% effective in reducing risk of HIV acquisition from IV drug use, when taken as prescribed.
CDC - PREP GUIDANCE
CDC - PREP GUIDANCE
Who should receive PrEP?
Patients at the highest risk are those who do not have HIV, but are known to have a male sexual partner that is infected with HIV (a “sero-discordant couple”).
Other high-risk candidates where PrEP should be prescribed:
Engage in sexual activity within high HIV-prevalence area or social network, with:
Limited or no condom use
Diagnosis of other STIs
Use of IV drugs or alcohol dependence, or both
Incarceration
Exchange of sex for commodities, such as drugs, shelter, food, or money
Otherwise – if your patient is sexually active, with a partner with unknown HIV status or if they’ve had a bacterial STI in the last six months – it’s a good idea to at least discuss PrEP!
Currently, the CDC has a very simple flowsheet for determining if PrEP prescriptions are immediately appropriate. But discuss with your sexually active patients!
Including adolescents – ACOG Practice Advisory was a limited update to encourage PrEP discussion in this population.
PrEP is OK for anyone > 35 kg / 77 lbs.
How should I prescribe PrEP?
Preparation:
Determine baseline HIV status with testing – if positive, need treatment, not PrEP
Remember – if they’ve had a potential HIV exposure or acute HIV infection symptoms in prior 4 weeks, may need re-testing before determining if they are positive.
Determine STI status for other infections such as gonorrhea, chlamydia, and syphilis.
Assess hepatitis B status
Because emtricitabine and tenofovir can be used to treat hepatitis B, it’s important to test for this – stopping the medicine suddenly in an infected person can lead to rebound hepatitis.
If HBV is found or a patient is known to be HBV positive → counsel about this risk and monitor LFTs / HBV viral loads if they discontinue PrEP.
Assess kidney function:
Oral tenofovir can cause some minor renal damage, and rarely acute renal failure.
If CrCl > 60 mL/min, OK to proceed with oral PrEP.
If CrCl > 30 mL/min, OK to proceed with injectable PrEP (more on that later!)
Assess lipid profile:
Oral PrEP may cause changes in lipid profile – baseline assessment should be performed with triglycerides.
Same day prescribing of PrEP is OK for most patients as these labs are drawn – but do not prescribe in patients where testing can’t be obtained, patients with concerning history for acute HIV infection or renal disease/associated conditions, or without confirmed means of contact for discussing lab results.
Medications and Monitoring:
Daily Oral PrEP:
Truvada or Descovy (both are combinations of emtricitabine and tenofovir)
Truvada has been approved for heterosexual women, as well as MSM and trans women.
Descovy has been approved only for MSM and trans women (not for heterosexual women).
Patients should be monitored with:
HIV testing q3 months
Syphilis, gonorrhea, chlamydia testing approximatley every 6 months
Creatinine clearance estimate every 6 months
Lipid panel yearly
Injectable PrEP:
Relatively new (Dec. 2021): injectable cabotegravir (brand name: Apretude)
FDA approved for heterosexual women, MSM, and trans women at risk of HIV infection.
Injection schedule is 2 injections x 1 month apart, followed by q2 month injection.
Patients should be monitored with recommended surveillance STI testing:
HIV testing with every injection visit
Gonorrhea, chlamydia, syphilis on an approximately every 6 month basis.
2-1-1 Oral PrEP
This is event-driven / “coitally-timed” PrEP.
This can be used by adult MSM, but is not recommended by the CDC and not FDA approved at this time.
It hasn’t been studied in heterosexual women or trans patients.
What if my patient becomes pregnant on PrEP?
Women seeking to conceive and pregnant/breastfeeding women can use oral PrEP.
Important to understand in HIV is the “undetectable, untransmissible” or U/U principle:
Women whose sexual partner has a viral load <200 copies/mL have effectively no risk of sexual acquisition.
If partner remains on maximally effective antiretroviral therapy and has undetectable VL, PrEP may not provide additional protective benefit.
PrEP may be continued if desired, and a antiretroviral pregnancy registry is available to prospectively and anonymously submit information to obtain further data (www.apregistry.com)
Further info
The CDC maintains a very extensive prescriber’s guide that is worth looking through to implement your own PrEP practice!
There is also a National Clinician Consultation Center at 855-448-7737 (855-HIV-PREP) that is available 9A to 8P ET on M-F to have clinician consultation for testing, prevention, treatment, and pre-exposure prophylaxis, and post-exposure prophylaxis resources.
The ACOG Practice Advisory also notes PrEP is widely covered with state Medicaid as preventive healthcare, and medication assistance is widely available – check out the end of the advisory for a list of resources.
