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 (June 2019)

The USPSTF recommendations do not yet reflect updated CDC guidance and currently recommends only offering PrEP to persons at high risk of HIV acquisition. This recommendation is Grade A, which means that PrEP should be offered or provided in the appropriate clinical settings (see below). In addition, the USPSTF document states that while PrEP is associated with “small harms” (e.g., kidney and GI events), overall

The USPSTF found convincing evidence that PrEP is of substantial benefit for decreasing the risk of HIV infection in persons at high risk of HIV infection, either via sexual acquisition or through injection drug use. The USPSTF also found convincing evidence that adherence to PrEP is highly correlated with its efficacy in preventing the acquisition of HIV infection.

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 because 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

Note: Newly FDA approved! (as of December 2021)

  • 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

Learn More – Primary Sources:

CDC: Pre-Exposure Prophylaxis (PrEP)

NIH: Pre-Exposure Prophylaxis (PrEP)

Preexposure Prophylaxis for the Prevention of HIV Infection: US Preventive Services Task Force Recommendation Statement (JAMA) 

USPSTF: Prevention of Human Immunodeficiency Virus (HIV) Infection: Pre-Exposure Prophylaxis (USPSTF)

ACOG Committee Opinion 595: Preexposure Prophylaxis for the Prevention of Human Immunodeficiency Virus

CDC PEP Guidelines

Screening & Treatment of Gynecologic infections in the HIV-Positive Woman

Gynecologic infections are more common, and may be more difficult to eradicate, in the HIV population.  Overall, treatment protocols remain the same, irrespective of HIV status, although there are some differences depending on the disorder.

CLINICAL ACTIONS:

  • Screen at entry to care and at least annually for the following: N. gonorrhoeae, C. trachomatis, syphilis and vaginal trichomoniasis
  • Screen for hepatitis C on entry to care
    • At-risk seronegative individuals should be screened at least annually
  • Consider type specific HSV serologic testing for those presenting for an STD evaluation
    • Approximately 70% of persons with HIV are HSV-2 seropositive | 95% are seropositive for either HSV-1 or HSV-2
    • HSV-2 infection increases the risk of HIV acquisition two- to three-fold and in coinfected patients
    • HSV-2 reactivation results in increases in HIV RNA levels in blood and genital secretions
  • Screen on entry to care for hepatitis B with HBsAg, anti-HBc and/or anti-HBs
    • Offer vaccination to seronegative individuals with hepatitis B or combined hepatitis A and B vaccine
    • Recheck immunity after vaccination complete

SYNOPSIS:

While it is critical to remain vigilant with regard to STDs and pelvic infections, women with ulcerative conditions of the genitalia, including syphilis and herpes, are at increased risk of HIV acquisition and transmission to partners, lending an urgency to prompt treatment or suppression (see separate entry on ulcerative conditions).

KEY POINTS:

  • Bacterial vaginosis is more prevalent/persistent in HIV-positive women
    • Diagnosis and treatment options are the same
  • Vulvovaginal candidiasis is more common among HIV-positive women and associated with decreased CD4+ counts
    • Treatment is the same as for HIV-negative women
    • For azole-refractory Candida glabrata vaginitis
      • Boric acid 600 mg vaginal suppository once daily for 14 days
    • Note: Severe or recurrent vaginitis should be treated with oral fluconazole (100 to 200 mg) or topical antifungals for ≥7 days
  • Treatment for gonorrhea/chlamydia is the same as for HIV-negative women
    • Retest 3 months after treatment as reinfection is common
  • Pelvic inflammatory disease is treated with the same antimicrobials for the same duration as for HIV-negative
    • There is a greater incidence of tubo-ovarian abscess among HIV-positive, but overall response to therapy is the same as for HIV-negative
  • Trichomoniasis is more prevalent among HIV-positive and should be treated with a one week course of metronidazole
  • Parasitic conditions such as scabies or pediculosis pubis are treated the same regardless of HIV status

Learn More – Primary Sources:

ACOG Practice Bulletin 167: Gynecologic Care for Women and Adolescents with Human Immunodeficiency Virus

NIH Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

CDC: Sexually Transmitted Infections Treatment Guidelines 2021

Ulcerative Genital Conditions in the HIV-Positive Woman

Genital, anal, or perianal ulcers are generally caused by syphilis or herpes.  Chancroid, lymphogranuloma venereum (LGV), and granuloma inguinale (donovaniasis) are less likely diagnoses; however, all these conditions are associated with increased HIV acquisition and transmission.  Guidelines for screening and treatment differ in some cases from those for the HIV-negative patient.

CLINICAL ACTIONS:

  • Evaluate first for herpes and syphilis first
  • Other causes such as chancroid and lymphogranuloma venereum should then be considered

Herpes Simplex (HSV)
Syphilis
Chancroid
Lymphogranuloma Venereum (LGV)
Granuloma Inguinale (donovaniasis)

Herpes Simplex lesions:

  • Caused by herpes simplex viruses (HSV)
  • Common and may be severe, painful and atypical
  • Offer HSV type-specific serologic testing on initial HIV evaluation for asymptomatic individuals
    • HSV DNA polymerase chain reaction (PCR) and viral culture are preferred methods for diagnosis of mucocutaneous HSV lesions caused by HSV
  • Consider suppression or episodic therapy to decrease clinical manifestations if HSV-2 is detected
    • Does not reduce risk for HIV transmission or HSV-2 transmission to susceptible sex partners
    • Generally higher doses/longer duration of treatment are recommended for HIV-positive women

Daily suppression

  • Acyclovir 400-800 mg BID or TID

or

  • Valacyclovir 500 mg BID

or

  • Famciclovir 500 mg BID

Episodic flares

  • Acyclovir 400 mg TID x 5-10 days

or

  • Valacyclovir 1 g BID x 5-10 days

or

  • Famcycolovir 500 mg BID x 5-10 days

Syphilis:

  • Systemic disease caused by Tremonema Pallidum
  • Primary syphilis is characterized by genital ulcers, though secondary/ tertiary/latent forms are not
  • A presumptive diagnosis of syphilis requires a treponemal test (i.e fluorescent treponemal antibody absorbed tests [FTA-ABS]) plus a nontreponemal test (i.e. Venereal Disease Research Laboratory [VDRL] or Rapid Plasma Reagin [RPR])
  • Screen for syphilis on initial HIV evaluation and annually thereafter
  • Treatment is the same regardless of HIV status
    • Penicillin G IM is the preferred treatment for all stages; the preparation (benzathine, aqueous procaine aqueous crystalline), dosage and length of treatment depend on the stage

Chancroid:

  • Painful, genital ulcers with suppurative lymphadenopathy caused by ducreyi
    • Treatment is the same regardless of HIV status
    • Close follow up is required as treatment failure is increased in the HIV positive

Treatment

  • Azithromycin 1 gm po

or

  • Ceftriaxone 250 mg IM

or

  • Ciprofloxacin 500 mg po BID x 3 days

or

  • Erythromycin 500 mg tid x 7 days

Lymphogranuloma Venereum (LGV)

  • Tender, unilateral groin/femoral lymphadenopathy with a self-limited genital ulcer/papule caused by C. trachomatis serovars L1, L2, or L3
  • Proctitis may occur
  • Diagnose by identifying C. trachomatis from the lesion by culture, direct immunofluorescence or nucleic acid detection
  • Treatment is the same regardless of HIV status

Treatment

  • Doxycycline 100 mg BID x 3 weeks

or

  • Erythromycin base 500 mg QID x 3 weeks

Granuloma Inguinale (Donovanosis):

  • Painless ulcerative disease characterized by beefy red, highly vascular lesions caused by Klebsiella granulomatis
  • Diagnose by identifying dark-staining “Donovan Bodies” on biopsy or tissue
  • Treatment is the same regardless of HIV status

Treatment  

  • Azithromycin 1 gm once/week or 500 mg/day x 3 weeks/until lesions healed

or

  • Doxycycline 100 mg BID X 3 weeks/until lesions healed

or

  • Ciprofloxacin 750 mg BID x 3 weeks/until lesions healed

or

  • Erythromycin base 500 mg QID x 3 weeks/until lesions healed

or

  • Trimethoprim-sulfamethoxazole double strength BID x 3 weeks/until healed

SYNOPSIS:

Vaginal, vulvar, and sexually transmitted infections may increase the risk of HIV transmission.  Prompt diagnosis and treatment decreases the likelihood of transmission; public health standards require providers to presumptively treat any patient, regardless of HIV status, with suspected syphilis immediately and before test results are available.  Presumptive treatment of primary herpes is also recommended as early treatment maximizes success.

KEY POINTS:

  • Genital, anal, or perianal lesions may not necessarily be infectious (e.g. trauma, carcinoma, aphthous, drug eruption, psoriasis)
  • Medical history and physical exam findings are frequently inaccurate and should be followed by tests that reflect conditions prevalent in the area
  • Consider biopsy for ulcers not responding to therapy or if the diagnosis is unclear
  • If HIV status is unknown, HIV testing should be offered to any woman with genital/anal ulcers presenting for treatment.

Diagnosis codes:

  • D28.9 benign neoplasm of female genital organs, unspecified
  • Z21 HIV infection

Learn More – Primary Sources:

2015 Sexually Transmitted Disease Treatment Guidelines

ACOG Practice Bulletin 167: Gynecologic Care for Women and Adolescents with Human Immunodeficiency Virus

NIH Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents