Post-exposure HIV prophylaxis

The goal of post-exposure prophylaxis (PEP) is to reduce the risk of transmission of HIV following accidental exposure to the virus. It is most efficacious if started within 72 hours of exposure.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf [49]New York State Department of Health AIDS Institute. PEP to prevent HIV infection. Aug 2023 [internet publication]. https://www.hivguidelines.org/pep-for-hiv-prevention The recommended treatment duration is 28 days.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf [4]Centers for Disease Control and Prevention; US Department of Health and Human Services. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. May 2018 [internet publication]. https://stacks.cdc.gov/view/cdc/38856 [46]World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach, 2nd ed. 2016 [internet publication]. https://apps.who.int/iris/handle/10665/208825 Treatment must be adhered to strictly, and timing must be observed to maximize the effect of PEP.

Indications for PEP

A decision can be made as to whether to offer PEP once the type and timing of exposure has been established (see Diagnostic approach). 

The following include recommendations for sexual, occupational, and other exposures.

Sexual exposures[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

• Receptive anal sex:

  • Source HIV-positive and viral load unknown or detectable: PEP recommended

  • Source HIV-positive and viral load undetectable: PEP not recommended

  • Unknown HIV status of source and from high-prevalence country or risk group: PEP recommended

  • Unknown HIV status of source and from low-prevalence country or risk group: PEP not recommended.

• Insertive anal sex:

  • Source HIV-positive and viral load unknown or detectable: PEP recommended

  • Source HIV-positive and viral load undetectable: PEP not recommended

  • Unknown HIV status of source and from high-prevalence country or risk group: consider PEP

  • Unknown HIV status of source and from low-prevalence country or risk group: PEP not recommended.

• Receptive vaginal sex:

  • Source HIV-positive and viral load unknown or detectable: PEP recommended

  • Source HIV-positive and viral load undetectable: PEP not recommended

  • Unknown HIV status of source and from high-prevalence country or risk group: generally not recommended

  • Unknown HIV status of source and from low-prevalence country or risk group: PEP not recommended.

• Insertive vaginal sex:

  • Source HIV-positive and viral load unknown or detectable: consider PEP

  • Source HIV-positive and viral load undetectable: PEP not recommended

  • Unknown HIV status of source and from high-prevalence country or risk group: generally not recommended

  • Unknown HIV status of source and from low-prevalence country or risk group: PEP not recommended.

• Fellatio with ejaculation, fellatio without ejaculation, splash of semen into eye, or cunnilingus: PEP not recommended..

Occupational and other exposures[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

• Sharing of injecting equipment, sharps injury, or mucosal splash injury:

  • Source HIV-positive and viral load unknown or detectable: PEP recommended

  • Source HIV-positive and viral load undetectable: PEP not recommended

  • Unknown HIV status of source and from high-prevalence country or risk group: generally not recommended

  • Unknown HIV status of source and from low-prevalence country or risk group: PEP not recommended.

• Human bite:

  • Source HIV-positive and viral load unknown or detectable: PEP generally not recommended

  • Source HIV-positive and viral load undetectable: PEP not recommended

  • Unknown HIV status of source and from high-prevalence country or risk group: PEP not recommended

  • Unknown HIV status of source and from low-prevalence country or risk group: PEP not recommended.

• Needlestick from a discarded needle in the community:

  • Unknown HIV status of source and from high-prevalence country or risk group: PEP not recommended

  • Unknown HIV status of source and from low-prevalence country or risk group: PEP not recommended.

Recommended, considered, generally not recommended, and not recommended can be classified as follows:[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

• Recommended: if the benefits of PEP are likely to outweigh the risks, PEP should be given unless there is a clear reason not to.

• Considered: the risk of HIV transmission is low, the risk-to-benefit balance of offering PEP is less clear, and should be assessed on a case-by-case basis taking into consideration factors listed below.

• Generally not recommended: the risk of HIV transmission is very low, and the potential toxicity and inconvenience of PEP is likely to outweigh the benefit unless there is a clear, specific, and extenuating factor that increases the risk. Generally associated with <1 in 10,000 risk of HIV transmission, but specific factors may increase risk.

• Not recommended: the risk of HIV transmission is negligible, and PEP should not be offered.

The strength of recommendation may be altered in the following circumstances:[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

• Sexual assault, as the transmission of HIV is believed more likely in cases of aggravated sexual intercourse (anal or vaginal)

• The presence of concurrent STI

• Multiple episodes of sexual exposure within a short time period

• Other risk factors (e.g., oropharyngeal or genital trauma/ulceration)

• Deep trauma or bolus of blood injected

• Knowledge of viral load or HIV viremia prevalence in the source population.

For exposures from a human bite, PEP should only be considered if there was blood in the saliva or a high viral load in the source, or if deep wounds were inflicted.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

Some patients may be extremely risk averse and request PEP after an exposure for which it is not usually recommended. Calculating the likely HIV transmission risk relating to the exposure may be helpful in reassuring these patients. A thorough explanation of the risks and benefits of PEP, including potential toxicities of the medications, should be given. The decision to offer PEP should be based on the risk of HIV acquisition and not to manage a state of acute anxiety following potential HIV exposure.

PEP regimens: general principles

The Centers for Disease Control and Prevention (CDC) and the UK British Association for Sexual Health and HIV (BASHH) both recommend a 3-drug regimen.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf [4]Centers for Disease Control and Prevention; US Department of Health and Human Services. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. May 2018 [internet publication]. https://stacks.cdc.gov/view/cdc/38856  The World Health Organization (WHO) states that a 2-drug regimen is effective, but a 3-drug regimen is preferred.[58]World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV. Jan 2018 [internet publication]. https://www.who.int/publications/i/item/WHO-CDS-HIV-18.51

The following factors must be taken into consideration when deciding which antiretroviral regimen to use:

• Whether the source is HIV-positive and whether they are likely to have a detectable viral load

• Which antiretrovirals the source is taking and whether they have any known HIV viral resistance

• The patient’s previous medical and drug history, including over-the-counter medications, as these may interact with antiretroviral medications.

If there is HIV viral resistance in the source, specialist advice will need to be sought to determine the most appropriate PEP regimen. Contraindications the patient may have to specific antiviral agents should also be taken into account.

There are significantly fewer drug-drug interactions with integrase strand transfer inhibitor-based regimens compared with protease inhibitor-based regimens. It is therefore important to thoroughly investigate possible drug-drug interactions when prescribing a protease inhibitor-based regimen.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are not routinely recommended for PEP due to the high prevalence of resistance. In the UK, the prevalence of NNRTI resistance was reported to be 4.2% in 2016.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

PEP regimens: nonpregnant adults and adolescents with normal renal function

The CDC recommends the following PEP regimens in adults and adolescents with normal renal function:[4]Centers for Disease Control and Prevention; US Department of Health and Human Services. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. May 2018 [internet publication]. https://stacks.cdc.gov/view/cdc/38856

• Emtricitabine/tenofovir disoproxil plus raltegravir or dolutegravir

• Emtricitabine/tenofovir disoproxil plus darunavir/ritonavir as an alternative.

The BASHH recommends the following PEP regimens in adults and adolescents with normal renal function:[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

• Emtricitabine/tenofovir disoproxil plus raltegravir

• Emtricitabine/tenofovir disoproxil plus elvitegravir/cobicistat as an alternative.

The WHO recommends the following PEP regimens in adults and adolescents with normal renal function:[58]World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV. Jan 2018 [internet publication]. https://www.who.int/publications/i/item/WHO-CDS-HIV-18.51

• Tenofovir disoproxil plus emtricitabine or lamivudine as the preferred backbone

• Dolutegravir as the preferred third drug; however, alternatives include atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, or raltegravir.

Laboratory research and clinical trials have shown excellent tolerability and efficacy of emtricitabine/tenofovir disoproxil plus raltegravir.[59]Mayer KH, Mimiaga MJ, Gelman M, et al. Raltegravir, tenofovir DF, and emtricitabine for postexposure prophylaxis to prevent the sexual transmission of HIV: safety, tolerability, and adherence. J Acquir Immune Defic Syndr. 2012 Apr 1;59(4):354-9. http://www.ncbi.nlm.nih.gov/pubmed/22267017?tool=bestpractice.com [60]Quah SP, McIntyre M, Wood A, et al. Once-daily raltegravir with tenofovir disoproxil/emtricitabine as HIV post-exposure prophylaxis following sexual exposure. HIV Med. 2021 Feb;22(2):e5-6. http://www.ncbi.nlm.nih.gov/pubmed/33063431?tool=bestpractice.com

PEP regimens: nonpregnant adults and adolescents with renal impairment

The CDC recommends the following PEP regimens in adults and adolescents with renal impairment:[4]Centers for Disease Control and Prevention; US Department of Health and Human Services. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. May 2018 [internet publication]. https://stacks.cdc.gov/view/cdc/38856

• Zidovudine plus lamivudine plus raltegravir or dolutegravir

• Zidovudine plus lamivudine plus darunavir/ritonavir as an alternative.

The BASHH recommends the following PEP regimens in adults and adolescents with renal impairment:[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

• Emtricitabine/tenofovir alafenamide plus raltegravir (reduced dose) or dolutegravir

• Emtricitabine/tenofovir alafenamide plus darunavir/ritonavir or atazanavir/ritonavir

• Emtricitabine/tenofovir alafenamide plus elvitegravir/cobicistat as an alternative.

The WHO does not make any specific recommendations for people with renal impairment.[58]World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV. Jan 2018 [internet publication]. https://www.who.int/publications/i/item/WHO-CDS-HIV-18.51

Tenofovir is available as tenofovir disoproxil or the oral prodrug tenofovir alafenamide. The BASHH recommends tenofovir alafenamide in preference to tenofovir disoproxil in patients with renal impairment as the prodrug is associated with less renal toxicity.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf  As the CDC guidelines are older, they do not currently recommend tenofovir alafenamide as an option in these patients. 

For patients with severe renal impairment (estimated glomerular filtration rate <30 mL/minute), expert advice should be sought from a specialist.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

PEP regimens: pregnant or breastfeeding women

Pregnancy is not a contraindication for PEP, and the regimens used in nonpregnant individuals may be used in pregnant women. However, an appropriate regimen should be selected under specialist consultation. All women of childbearing potential should have a pregnancy test before starting PEP.

There was previously a concern that dolutegravir may increase the risk of neural tube defects in infants born to women who conceived while taking the drug, based on an interim analysis of data from a surveillance study in Botswana. However, more recent studies have found the risk to be lower than initially thought, and the most recent data from the Botswana study indicate that the prevalence of neural tube defects was not significantly different than in those receiving other retrovirals. US guidelines therefore consider the use of dolutegravir to be safe throughout pregnancy.[49]New York State Department of Health AIDS Institute. PEP to prevent HIV infection. Aug 2023 [internet publication]. https://www.hivguidelines.org/pep-for-hiv-prevention

Despite this, the UK BASHH guidelines recommend avoiding dolutegravir as the third drug in women at risk of pregnancy or known to be within the first 6 weeks of pregnancy who cannot use a first-line PEP regimen for any reason. However, it may be used in pregnant women who are more than 6 weeks pregnant.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf  The WHO recommends that the use of dolutegravir is conditional upon access to consistent and reliable contraception.[58]World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV. Jan 2018 [internet publication]. https://www.who.int/publications/i/item/WHO-CDS-HIV-18.51 However, it should be noted that both of these guidelines were published before the current US guidelines.

Breastfeeding is not a contraindication for PEP, but women should be counseled on the risk of infant exposure to antiretrovirals via breastmilk.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

PEP regimens: children

There are few data regarding the administration of PEP to children. The choice of antiretroviral regimen depends on the child’s age. The dosing of antiretrovirals is weight-based for some regimens. Some medications come in liquid formulations that can be easier for children to take. It is advisable to consult with a pediatric HIV specialist if considering PEP in children. Specific details on PEP regimens in children are beyond the scope of this topic.

Children and adolescents who have been sexually assaulted should ideally be managed in the emergency department or other setting where age-appropriate resources are available to address the multiple medical, psychosocial, and legal issues related to such an offense.

PEP: adverse effects

In a study of 100 patients treated with emtricitabine/tenofovir plus raltegravir for PEP, the side effects were almost universally rated as mild, with less than 30% of patients reporting each of the following side effects: diarrhea, nausea/vomiting, fatigue, headache, dizziness, and abdominal discomfort.[59]Mayer KH, Mimiaga MJ, Gelman M, et al. Raltegravir, tenofovir DF, and emtricitabine for postexposure prophylaxis to prevent the sexual transmission of HIV: safety, tolerability, and adherence. J Acquir Immune Defic Syndr. 2012 Apr 1;59(4):354-9. http://www.ncbi.nlm.nih.gov/pubmed/22267017?tool=bestpractice.com Antiemetics and antimotility agents are not routinely required. If an individual had previous experiences with toxicity or other side effects while taking PEP, alternative regimens may be prescribed. However, if the adverse events were mild and alternatives are not readily available, PEP should not be delayed and may be switched later when practical. 

Renal toxicity with PEP is rare; renal function should be monitored in patients with previous renal impairment during treatment, and in all patients treated with tenofovir. Patients with hepatitis coinfection should be monitored for liver toxicity with PEP, although severe liver adverse effects are uncommon even in this group.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf  

Integrase strand transfer inhibitors may be associated with myopathy or rhabdomyolysis, so creatinine kinase should be measured if these symptoms are reported after starting PEP, and caution should be used in individuals with a history of myopathy and in those using other myopathy-associated medications (e.g., statins).[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf

Counseling and support

Counseling is an important step in the management of PEP. The purpose, rationale, and efficacy of PEP should be explained so that the patient can make an informed decision whether to start the regimen.

The importance of completing the full 28-day regimen should be stressed. Adherence to a full 28-day course of PEP has been shown to be poor in multiple studies.[61]Ford N, Irvine C, Shubber Z, et al. Adherence to HIV postexposure prophylaxis: a systematic review and meta-analysis. AIDS. 2014 Nov 28;28(18):2721-7. http://www.ncbi.nlm.nih.gov/pubmed/25493598?tool=bestpractice.com Adherence counseling may help with this, especially if psychosocial stressors affecting adherence can be addressed.[62]Blashill AJ, Ehlinger PP, Mayer KH, et al. Optimizing adherence to preexposure and postexposure prophylaxis: the need for an integrated biobehavioral approach. Clin Infect Dis. 2015 Jun 1;60 Suppl 3:S187-90. https://cid.oxfordjournals.org/content/60/suppl_3/S187.long http://www.ncbi.nlm.nih.gov/pubmed/25972502?tool=bestpractice.com Medication should be started as soon as possible and taken each day according to the schedule that best fits the patient’s daily routine, in order to encourage adherence. People should be warned about adverse effects (e.g., fatigue, headache, rash, nausea, and diarrhea) and toxicities (e.g., liver dysfunction and anemia).

Counseling should address risk reduction strategies for the future and the importance of safe sex, especially in the HIV-testing window period. This is particularly important in people who have had multiple sexual exposures to HIV, and may offer an opportunity to discuss the potential for high-risk individuals to transition to pre-exposure prophylaxis (PrEP) when PEP is completed.[3]British Association for Sexual Health and HIV. UK guideline for the use of HIV post-exposure prophylaxis. 2021 [internet publication]. https://www.bashhguidelines.org/media/1308/pep-2021.pdf [42]Jain S, Krakower DS, Mayer KH. The transition from postexposure prophylaxis to preexposure prophylaxis: an emerging opportunity for biobehavioral HIV prevention. Clin Infect Dis. 2015 Jun 1;60 Suppl 3:S200-4. https://cid.oxfordjournals.org/content/60/suppl_3/S200.long http://www.ncbi.nlm.nih.gov/pubmed/25972505?tool=bestpractice.com

Patients should be warned about potential drug-drug interactions with the PEP regimen. This must include over-the-counter medications (including herbal or alternative medicines) as well as prescribed medications.

HIV pretest discussion should be carried out prior to the baseline HIV test, and investigations and importance of follow-up made clear. Patients should also be counseled regarding the symptoms of seroconversion. Flu-like illness with fever, sore throat, rash, or diarrhea may occur, but more severe symptoms have also been documented. This may occur up to 12 weeks after exposure.[55]Mindel A, Tenant-Flowers M. ABC of AIDS: Natural history and management of early HIV infection. BMJ. 2001 May 26;322(7297):1290-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1120386 http://www.ncbi.nlm.nih.gov/pubmed/11375235?tool=bestpractice.com

People who have been either occupationally or sexually exposed to HIV may need close psychological support (this may apply especially to those who have been sexually assaulted). Patients who have been exposed to HIV through rape or other sexual assaults should be offered a referral to a rape crisis group and should receive support from social workers and case managers, including discussion of any ongoing domestic violence risk.