What is the recommended postexposure prophylaxis (PEP) regimen for nonoccupational exposure to HIV?

Updated: Jul 27, 2020
  • Author: Ana Elizabeth Markelz, MD, FACP, FIDSA; Chief Editor: John Bartlett, MD  more...
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Answer

Answer

The 2016 guidelines for antiretroviral postexposure prophylaxis for nonoccupational exposure to HIV recommend either raltegravir (RAL) 400 mg twice daily or dolutegravir (DTG) 50 mg daily in combination with tenofovir disoproxil fumarate (TDF) 300 mg and emtricitabine (FTC) 200 mg daily as the preferred regimen in healthy adults and adolescents. [10] Dolutegravir provides a reasonable once-daily alternative to raltegravir. This ART regimen is not in the 2013 postoccupational exposure to HIV guidelines since it was FDA-approved after the PEP guidelines were written but is favored by most authorities.

In May 2018, the CDC and FDA issued guidance to avoid dolutegravir (DTG) based on data from surveillance studies suggesting an increased risk of neural tube defects associated with exposure to dolutegravir (DTG) at conception. [11] Since then, additional data have demonstrated less risk than previously thought. The Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission removed restrictions on the use of DTG in women who are trying to conceive and during the first trimester of pregnancy based on data as of August 2019. [12] In addition, DTG was selected as a preferred antiretroviral medication during pregnancy and as an alternative antiretroviral medication for women trying to conceive. [12] The surveillance data from Botswana revealed a higher prevalence of neural tube defects in infants born to women taking dolutegravir (0.3%; 95% CI, 0.12-0.69) compared with other antiretroviral regimens (0.1%; 95% CI, 0.06-0.17). [13] In contrast, the same group did not identify any birth defects among 280 infants born to women who initiated DTG after 4 weeks of conception or among 729 infants born to women who initiated DTG in the second or third trimester. [14]

The CDC has not updated their guidance. The CDC still recommends that healthcare providers avoid DTG for PEP in the following patients: [11]

  • Nonpregnant women of childbearing potential who are not on an effective birth control method who are sexually active or who have been sexually assaulted
  • Pregnant women who are early in their pregnancy (within the first 28 days)

In these situations, according to CDC guidance, the preferred PEP regimen is raltegravir, tenofovir, and emtricitabine. For situations of intolerability or unavailability of the medications, the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline) should be contacted at 888-448-4911 daily from 9 am to 2 am EST (6 am to 11 pm PST) for alternative PEP options. The Antiretroviral Pregnancy Registry can be contacted at 800-258-4263. [11]

All women of childbearing potential should have undergo pregnancy testing prior to initiation of PEP. A nonpregnant woman of childbearing potential who is prescribed dolutegravir should be counseled to use an effective birth control method until she completes the PEP regimen. Pregnant women exposed to DTG should be monitored for neural tube defects, especially if the exposure occurred during the first trimester. [11]

A 2016 randomized prospective noninferiority study of ritonavir-boosted darunavir (DRV/r) versus the standard of care (SOC) for HIV PEP concluded that DRV/r should be included as a standard component of recommended regimens in PEP guidelines. The recommendation was based on the tolerability and safety profile of DRV/r. [15]

Table 2. Information on HIV PEP Medications [2] (Open Table in a new window)

Drug name

Drug class

Dosing (dosage form)

Advantages

Disadvantages

Abacavir (Ziagen; ABC)

NRTI

ABC: 300 mg daily; available as 300-mg tablet

Also available as component of fixed-dose combination Epzicom, dosed daily (300 mg of 3TC + 600 mg of ABC)

Trizivir, dosed twice daily (150 mg of 3TC + 300 mg of ABC + 300 mg of AZT)

Take without regard for food

Potential for life-threatening ABC hypersensitivity reaction (rash, fever, nausea, vomiting, diarrhea, abdominal pain, malaise, respiratory symptoms) in patients with HLA-B*5701; requires patient testing prior to use, which may not be available or practical prior to initiating PEP

Atazanavir (Reyataz; ATV)

PI

ATV: 300 mg + RTV: 100 mg once daily (preferred dosing for PEPa)

ATV: 400 mg once daily without RTV (alternative dosing—may not be used in combination with TDF)

Available as 100-, 150-, 200-, and 300-mg capsules

Well tolerated

Indirect hyperbilirubinemia and jaundice common

Rash

Nephrolithiasis

Potential for serious or life-threatening drug interactions that may affect dosing

Absorption depends on low pH; caution when coadministered with H2 antagonists, antacids, and proton pump inhibitors

PR interval prolongation

Caution in patients with underlying conduction defects or on concomitant medications that can cause PR prolongation

Must be given with food

Darunavir (Prezista; DRV)

PI

DRV: 800 mg once daily + RTV: 100 mg once daily (preferred dosing for PEPa )

DRV: 600 mg twice daily + RTV: 100 mg twice daily (alternative dosing)

Available as 75-, 150-, 400-, and 600-mg tablets

Well tolerated

Rash (DRV has sulfonamide moiety)

Diarrhea, nausea, headache

Hepatotoxicity

Potential for serious or life-threatening drug interactions that may affect dosing

Must be given with food and with RTV

Dolutegravir

(Tivicay; DTG)

INSTI 50 mg daily; available as a 50-mg tablet

Once daily

Well tolerated

Take without regard for food

Do not use during pregnancy, especially during first trimester; associated with neural tube defects.

Dose adjustment to 50 mg twice daily required if coadministered with rifampin, fosamprenavir/ritonavir, tipranavir/ritonavir or efavirenz. Do not administer with polyvalent cations.

Insomnia, nausea, fatigue, headache, and severe skin and hypersensitivity reactions have been reported.

Efavirenz (Sustiva; EFV)

NNRTI

EFV: 600 mg daily; available as 50- and 200-mg capsules and 600-mg tablets

Also available as component of fixed-dose combination Atripla, dosed daily (200 mg of FTC + 300 mg of TDF + 600 mg of EFV)

Available as a complete regimen dosed once per day

Rash

Neuropsychiatric side effects (eg, dizziness, somnolence, insomnia, abnormal dreaming) common; severe psychiatric symptoms possible (dosing before bedtime might minimize these side effects); use with caution in shift workers

Do not use during pregnancy; teratogen in nonhuman primates

Potential for serious or life-threatening drug interactions that may affect dosing

May cause false-positive results with some cannabinoid and benzodiazepine screening assays Take on an empty stomach

Elvitegravir (EVG)

INSTI

Available as a component of fixed-dose combination Stribild, dosed daily (150 mg of EVG + 150 mg of cobicistat + 300 mg of TDF + 200 mg of FTC)

Well tolerated

Available as a complete regimen dosed once per day

Diarrhea, nausea, headache

Nephrotoxicity; should not be administered to individuals with acute or chronic kidney injury or those with eGFR < 70

Cobicistat is a pharmacokinetic enhancer to increase EVG exposures and has no antiviral activity but is a potent CYP3A inhibitor

Potential for serious or life-threatening drug interactions

Must be given with food

Emtricitabine (Emtriva; FTC)

NRTI

200 mg once daily; available as 200-mg capsule

Also available as component of fixed-dose combination Atripla, dosed daily (200 mg of FTC + 300 mg of TDF + 600 mg of EFV)

Complera, dosed daily (25 mg of RPV + 300 mg of TDF + 200 mg of FTC)

Stribild, dosed daily (150 mg of EVG + 150 mg of cobicistat + 300 mg of TDF + 200 mg of FTC)

Truvada, dosed daily (200 mg of FTC + 300 mg of TDF)

Well tolerated

Minimal toxicity

Minimal drug interactions

Take without regard for food

Rash perhaps more frequent than with 3TC

Hyperpigmentation/skin discoloration

If the PEP recipient has chronic hepatitis B, withdrawal of this drug may cause an acute hepatitis exacerbation

Enfuvirtide (Fuzeon; T20)

FI

T20: 90 mg (1 mL) twice daily by subcutaneous injection; available as single-dose vial, reconstituted to 90 mg/mL

---

Local injection-site reactions occur in almost 100% of patients

Never studied among antiretroviral-naive or HIV-negative patients

False-positive EIA HIV antibody tests might result from formation of anti-T20 antibodies that crossreact with anti-gp41 antibodies

Twice-daily injection

Etravirine (Intelence; ETR)

NNRTI

200 mg twice daily; available as 100- and 200-mg tablets

Well tolerated and has not had the same frequency of CNS side effects reported as EFV

Rash (including SJS) and hypersensitivity (sometimes with organ dysfunction, including hepatic failure)

Nausea

Potential for serious or life-threatening drug interactions that may affect dosing

Must be given with food

Fosamprenavir (Lexiva; FOSAPV)

PI

FOSAPV: 1,400 mg daily + RTV: 100 mg once daily (preferred dosing for PEP)

FOSAPV: 1,400 mg twice daily without RTV (alternative dosing)

Available as 700-mg tablet

Well tolerated

Diarrhea, nausea, vomiting, headache, rash (FOSAPV has sulfonamide moiety)

Potential for serious or life-threatening drug interactions that may affect dosing

Oral contraceptives decrease FOSAPV concentrations

Take with food if given with RTV

Lamivudine (Epivir; 3TC)

NRTI

3TC: 300 mg once daily (preferred dosing for PEP)

3TC: 150 mg twice daily (alternative dosing)

Available as 150- and 300-mg tablets

Also available as component of fixed-dose combination generic lamivudine/zidovudine, dosed twice daily (150 mg of 3TC + 300 mg of AZT)

Combivir, dosed twice daily (150 mg of 3TC + 300 mg of AZT)

Epzicom, dosed daily (300 mg of 3TC + 600 mg of ABC)

Trizivir, dosed twice daily (150 mg of 3TC + 300 mg of ABC + 300 mg of AZT)

Well tolerated

Minimal toxicity

Minimal drug interactions

Take without regard for food

If the PEP recipient has chronic hepatitis B, withdrawal of this drug may cause an acute hepatitis exacerbation

Lopinavir/ritonavir (Kaletra; LPV/RTV)

PI

Kaletra: 400/100 mg = 2 tablets twice daily (preferred dosing for PEP)

Kaletra: 800/200 mg = 4 tablets once daily (alternative dosing)

Available as 200/50-mg tablets

Take without regard for food

GI intolerance, nausea, vomiting, diarrhea are common

PR and QT interval prolongation have been reported; use with caution in patients at risk of cardiac conduction abnormalities or receiving other drugs with similar effect

Potential for serious or life-threatening drug interactions that may affect dosing

Maraviroc (Selzentry; MVC)

CCR5 coreceptor antagonist

MVC: 300 mg twice daily (if on concomitant CYP3A inducers, dose may need adjustment by expert consultant); available as 150- and 300-mg tablets

Well tolerated

Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, orthostatic hypotension

Hepatotoxicity that may present with an allergic reaction, including rash

Requires HIV tropism testing of source virus before treatment to ensure CCR5-tropic virus and efficacy, which may not be available or practical prior to initiating PEP

Potential for serious or life-threatening drug interactions that may affect dosing

Dose adjustments for MVC required when given with potent CYP3A inhibitors or inducers

Raltegravir (Isentress; RAL)

INSTI

400 mg twice daily; available as 400-mg tablet

Well tolerated

Minimal drug interactions

Take without regard for food

Insomnia, nausea, fatigue, headache, and severe skin and hypersensitivity reactions have been reported

Rilpivirine (Edurant; RPV)

NNRTI

25 mg once daily; available as 25- mg tablet

Also available as component of fixed-dose combination Complera, dosed daily (25 mg of RPV + 300 mg of TDF + 300 mg of FTC)

Well tolerated and fewer rashes and discontinuations for CNS adverse effects compared with EFV

Available as a complete regimen dosed once per day

Depression, insomnia, rash, hypersensitivity, headache

Potential for serious or life-threatening drug interactions that may affect dosing

Caution when coadministered with H2 antagonists and antacids

Coadministration with proton pump inhibitors is contraindicated

Use RPV with caution when coadministered with a drug having a known risk of torsades de pointes

Must be given with food

Saquinavir (Invirase; SQV)

PI

SQV: 1,000 mg + RTV: 100 mg twice daily (preferred dosing for PEP); available as 500 mg tablet

Well tolerated, although GI events common

GI intolerance, nausea, diarrhea, headache

Pretreatment ECG recommended

SQV/r is not recommended for patients with any of the following: (1) congenital or acquired QT prolongation, (2) pretreatment ECG 1450 msec, (3) receiving concomitant therapy with other drugs that prolong QT interval, (4) complete AV block without implanted pacemakers, and (5) risk of complete AV block

PR and QT interval prolongations, torsades de pointes has been reported

Potential for serious or life-threatening drug interactions that may affect dosing

Must be given with food

Stavudine (Zerit; d4T)

NRTI

d4T: 40 mg twice daily if body weight is >60 kg

d4T: 30 mg twice daily if body weight is < 60 kg

Available as 15-, 20-, 30-, and 40-mg tablets

Take without regard for food

GI side effects include diarrhea and nausea

Hepatotoxicity, neurologic symptoms (eg, peripheral neuropathy), pancreatitis

Tenofovir DF (Viread; TDF)

NRTI

300 mg once daily; available as 300-mg tablet

Also available as component of fixed-dose combination Atripla, dosed daily (200 mg of FTC + 300 mg of TDF + 600 mg of EFV)

Complera, dosed daily (25 mg of RPV + 300 mg of TDF + 200 mg of FTC)

Stribild, dosed daily (150 mg of EVG + 150 mg of cobicistat + 300 mg of TDF + 200 mg of FTC)

Truvada, dosed daily (200 mg of FTC + 300 mg of TDF)

Well tolerated

Take without regard for food

Asthenia, headache, diarrhea, nausea, vomiting

Nephrotoxicity; should not be administered to individuals with acute or chronic kidney injury or those with eGFR < 60

If the PEP recipient has chronic hepatitis B, withdrawal of this drug may cause an acute hepatitis exacerbation

Drug interactions

Zidovudine (Retrovir; ZDV; AZT)

NRTI

AZT: 300 mg twice daily; available as 100-mg capsule or 300- mg tablet

Also available as component of fixed-dose combination generic lamivudine/zidovudine, dosed twice daily (150 mg of 3TC + 300 mg of AZT)

Combivir, dosed twice daily (150 mg of 3TC + 300 mg of AZT)

Trizivir, dosed twice daily (150 mg of 3TC + 300 mg of ABC + 300 mg of AZT) Ta

Take without regard for food

Side effects (especially nausea, vomiting, headache, insomnia, and fatigue) common and might result in low adherence

Anemia and neutropenia

NOTE. This table does not provide comprehensive information on each individual drug. For detailed information, please refer to individual drug package inserts. AV, atrioventricular; CNS, central nervous system; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; EIA, enzyme immunoassay; GI, gastrointestinal; SJS, Stevens-Johnson syndrome.

a Certain antiretroviral agents, such as PIs, have the option of once- or twice-daily dosing depending on treatment history and use with ritonavir. For PEP, the selection of dosing and schedule is to optimize adherence while minimizing side effects where possible. This table includes the preferred dosing schedule for each agent, and in all cases with the exception of Kaletra the once-daily regimen option is preferred for PEP. Twice-daily administration of Kaletra is better tolerated with respect to GI toxicities compared with the once-daily regimen. Alternative dosing and schedules may be appropriate for PEP in certain circumstances and should preferably be prescribed by individuals experienced in the use of antiretroviral medications.


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