CDC Guidelines on Antiretroviral Preexposure Prophylaxis to Prevent HIV in Those at Risk

SUMMARY:

The CDC has published updated guidelines on the use of PrEP – a pharmacologic approach to reduce HIV risk. Guidelines now simplify counseling recommendations to include all sexually active adolescents and adults, and higher risk groups should be routinely prescribed PrEP. PrEP medication options are also expanding with two approved daily oral antiretroviral preexposure prophylaxis (PrEP) medications and an intramuscular antiretroviral medication pending FDA approval.

CDC Guidance

General Counseling and Offering of PrEP

All sexually active adults
- Should be counseled on risks of STI, including HIV
- Should be informed about PrEP to improve general awareness
PrEP can be prescribed after options-counseling to
- All HIV negative individuals who are interested and request PrEP and
- Weigh at least 35kg (77 lb)

Higher Risk Populations

PrEP should be routinely prescribed for all persons who are HIV negative and are at on-going higher risk for transmission of HIV, defined as
- Sexually active patients (anal or vaginal sex in the past six months) AND one of the following risk factors
  - HIV-positive sexual partner (especially if partner has unknown or detectable viral load) or
  - 1 or more sexual partners with unknown HIV status without consistent use of condoms or
  - Diagnosed with bacterial STI in the past 6 months | MSM diagnosed with gonorrhea, chlamydia, or syphilis | MSW and WSM diagnosed with GC or syphilis
- Persons without HIV who have injected drugs in the past 6 months and
  - HIV+ injecting partner or
  - Sharing injection equipment
- Persons who have been prescribed PEP (post-exposure prophylaxis) and
  - report continued risk behavior or
  - have used multiple courses of PEP

USPSTF Guidance

The USPSTF addresses PrEP and concludes that there is substantial net benefit to reduce the risk of HIV in persons at increase risk fo acquiring HIV (high certainty)

The USPSTF recommends that clinicians prescribe preexposure prophylaxis using effective antiretroviral therapy to persons at increased risk of HIV acquisition to decrease the risk of acquiring HIV (A recommendation)

What is PrEP

PrEP is an anti-retroviral medication (or medications) to prevent the transmission of HIV and not recommended for the treatment of HIV

Oral Formulations

Oral pill taken daily
- Emtricitabine (F) 200 mg and tenofovir disoproxil fumarate (TDF) 300 mg (F/TDF, Truvada) to prevent HIV infection among all persons at risk through sex or injection drug use
- Emtricitabine (F) 200 mg tenofovir alafenamide (TAF) 25 mg tablet (F/TAF, Descovy) taken daily to prevent HIV infection among persons at risk through sex, excluding people at risk through receptive vaginal sex due to lack of studies for this indication
Effectiveness estimates
- Sexual transmission route: approximately 99% effective
- Injection drug use: 74 to 84% effective (based on tenofovir alone and may be higher with combination pill)
- Effectiveness strongly related to adherence to PrEP

Intramuscular Formulation

Cabotegravir (600mg) is an IM injection in the gluteal muscle recommended (conditional on FDA approval) every 2 months
- In persons concerned about side effects, can consider a 30mg daily oral cabotegravir for a 4-week lead-in prior to injections

Clinical Actions

Clinical eligibility
- HIV testing confirming negative status before starting PrEP
- No signs/symptoms of acute HIV infection
- No contraindication or allergies to medications
- Recommended laboratory testing based on oral PrEP regimen versus IM PrEP regimen
- Document pregnancy intention
- Screen/treat STIs
Recommend regular monitoring of HIV infection status, side effects, adherence, and sexual or injection risk behaviors as well as STI testing, pregnancy testing, and additional laboratory results
Reinforce the importance of adherence and HIV risk reduction, including encouraging condom use for additional protection
While on oral PrEP, requires assessment of renal function at 3 months and every 6 months after, using Cockcroft-Gault formula
- F/TDF: Approved for use in persons with eCrCl >60 ml/min
- F/TAF: Approved for use in persons with eCrCl ≥30 ml/min
While on IM PrEP, does not require assessment of renal or liver function
STI screening should be administered every 6 months even if asymptomatic
Stop PrEP if
- Patient requests to stop | Counsel regarding other preventative measures
- Patient now HIV positive | Manage or refer for treatment

Dosage

Initiation of oral PrEP

Daily oral pill of F/TDF or F/TAF prescription
Limit prescription to a 90 day corresponding to every 3 month HIV testing
Prior to prescription, laboratory assessment requirements includes renal infection, hepatitis B virus infection, and lipid profile (F/TAF)
Side effects in clinical trials were mild | early side effects include mild GI distress that resolved the first month or headache
- Serious side effects are rare however can impair renal function | Serum creatinine monitoring required
- Liver function can be adversely affected and patients should report symptoms (e.g. tea colored urine, light colored stool etc.)

Intramuscular Regimen

Administration of cabotegravir 600mg via one 3mL intramuscular injection in the gluteal muscle | Initiation of cabotegravir requires a second dose 4 weeks after the first dose (one month follow up visit) and every 8 weeks after with HIV testing at visits
- Can consider trial of cabotegravir 30mg daily for four weeks prior to initiation of IM injections if patients are anxious about side effects
- Schedule is initial administration (month 0), one month after initiation (month 1), then every 8 weeks afterwards (month 3, 5, 7, etc.)
Follow-up visit one month after initial injection should include second dose and HIV Ag/Ab test and HIV-1 RNA assay with subsequent 2-month intervals
The following laboratory tests are NOT indicated before starting CAB injection or for monitoring patients during its use
- Creatinine or eCrCl
- hepatitis B serology
- lipid panels
- liver function tests
Minimal side effects were noted

PrEP Maintenance

Patients on PrEP should return to their health care provider every 3 months with oral PrEP and every 2 months for intramuscular PrEP and should include:
- HIV testing to ensure sero-negative
- Prescription refill
- Assess and counseling regarding medication adherence and risk reduction behaviors
- Laboratory testing including STIs and pregnancy
- Address any concerns, including side effects
Renal Assessment required for oral daily dosing of PrEP but not IM dosing of PrEP
- Patients <50 or with with eCrCl >90 at initiation should have renal function assessed every 12 months
- Impaired renal function should trigger evaluation every 6 months
- Thresholds | F/TDF: Approved for use in persons with a eCrCl >60 ml/min, F/TAF: Approved for use in persons with eCrCl ≥30 ml/min
- A rise in creatinine is not a reason to withhold treatment, as long as above the threshold as above

NOTE: Renal function monitoring not required with cabotegravir

Lipid panel is recommended annually in patients taking F/TAF
Hepatitis B serology testing is only recommended at initiation of PrEP
Hepatitis C testing is recommended annually for MSM, TGW, and PWID

HIV-discordant Couples and Pregnancy

Conception and pregnancy
- PrEP is one of several options to protect the partner who is HIV-negative (see related ‘ObG Topics, below) in a couple considering pregnancy
- Data on use of the PrEP medication has not shown increased risk of birth defects nor risk to breastfeeding children

Breastfeeding

The CDC states that “F/TDF as PrEP is considered generally safe for pregnant and breastfeeding women”
For F/TDF, the FDA label states

The health benefits of breastfeeding and the mother’s clinical need for PrEP should be considered along with any potential adverse effects on the breastfed child from TRUVADA balanced against the risks of HIV-1 acquisition due to nonadherence and subsequent mother to child transmission. Women should not breastfeed if acute HIV-1 infection is suspected because of the risk of HIV-1 transmission to the infant

PrEP vs PEP

PrEP is only for people who are at ongoing substantial risk of HIV infection
For a single high-risk event of potential HIV exposure (e.g., unprotected sex, needle-sharing injection drug use, or sexual assault—use postexposure prophylaxis (PEP) option, or PEP within 72 hours of exposure (see ‘Learn More – Primary Sources’ below)

KEY POINTS:

All sexually active adolescents and adults who are sexually active should be counseled on and offered PrEP regardless of risk designation

PrEP should be routinely prescribed for patients at higher risk of HIV acquisition, including:

Sexually active patients (anal or vaginal sex in the past six months) AND one of the following risk factors
- HIV-positive sexual partner (especially if partner has unknown or detectable viral load) or
- 1 or more sexual partners with unknown HIV status without consistent use of condoms or
- Diagnosed with bacterial STI in the past 6 months | MSM diagnosed with gonorrhea, chlamydia, or syphilis | MSW and WSM diagnosed with GC or syphilis
Persons without HIV who have injected drugs in the past 6 months and
- Have HIV+ injection partners or
- Share injection equipment
Persons who have been prescribed PEP (post-exposure prophylaxis) and
- report continued risk behavior or
- have used multiple courses of PEP