University of California, San Francisco |
Updated: January 31, 2023
This NCCC pre-exposure prophylaxis (PrEP) guide aims to provide a basic framework for clinicians and was developed based on commonly asked questions received on the NCCC’s PrEPline. Individualized consultation can be obtained by calling or submitting a question online: our PrEPline page lists current hours and availability. We also recommend the 2021 CDC PrEP Clinical Practice Guidelines Update as an additional information resource.
Commonly Asked Questions
Initial Evaluation: Deciding Whether to Start PrEP
What is PrEP?
Pre-exposure prophylaxis (or PrEP) is an HIV prevention method in which people who do not have HIV infection take medications in advance of a possible exposure, to reduce the likelihood of HIV acquisition. Currently, three medications are FDA-approved for PrEP: co-formulated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, Truvada®), co-formulated tenofovir alafenamide/emtricitabine (TAF/FTC, Descovy®), and injectable cabotegravir (LA-CAB, Apretude®).
How effective is PrEP?
Like all medications, PrEP works optimally when used as prescribed: CDC guidelines indicate that, when taken correctly, oral PrEP reduces the likelihood of sexual acquisition by 99%, and from injection drug use by 74%. Long-acting injectable cabotegravir is highly efficacious in preventing sexual acquisition of HIV. For all persons on PrEP, medication adherence should be reviewed regularly.
With whom should PrEP be discussed, and how can I introduce the topic?
2021 CDC Guidelines recommend that all sexually active adolescents and adults receive information about PrEP, and that it should be prescribed to anyone who requests it. PrEP may be especially important to offer to people who have recently been diagnosed with a bacterial STI, people who inject drugs, people whose sex partners are living with untreated HIV (or whose partners are receiving HIV treatment but experiencing viremia), and people who have sex partners of unknown HIV status.
Given ongoing disparities in PrEP access and utilization, and potentially stigmatizing language such as “HIV risk”, general counseling messages and questions may be considered – examples include:
• “Are you interested in hearing more about medications that can prevent HIV?”
• “Have you heard of PrEP?”
• “How do you think your [sex] life would improve if you didn’t have to worry about HIV?”
What is the difference between PEP and PrEP?
Post-exposure prophylaxis (PEP) refers to preventive medications started soon (i.e., within 72 hours) after a recent potential HIV exposure. This includes condomless insertive or receptive vaginal sex, condomless insertive or receptive anal sex, or shared use of equipment to prepare or inject drugs. Every person should be evaluated for possible indications for PEP prior to PrEP initiation. Individualized provider consultation is available by calling the NCCC PEPline.
What if someone had a potential HIV exposure within the last 4-6 weeks but is outside the CDC-recommended window for initiating PEP?
Assess for signs and symptoms of acute HIV infection, and consider reaching out to a local PrEP/PEP expert or the NCCC PrEPline.
How should patients on PEP be transitioned to PrEP?
Some people on PEP may prefer a seamless transition to PrEP, especially when ongoing exposures to HIV are anticipated. CDC’s PrEP Guidelines includes information on transitioning from non-occupational PEP to PrEP. Generally, for people who will transition from PEP immediately to PrEP, providers should:
• Screen for signs and symptoms of acute HIV infection during and after the 28-day PEP course.
• Obtain a “4th generation” HIV Ag/Ab test at time of PEP completion (or a few days prior to completion). Additional co-testing with HIV-1 RNA is also recommended (if available) at/around the time of PEP to PrEP transition. Complete any PrEP-related baseline laboratory testing not previously performed as part of the initial PEP evaluation.
• After confirming no clinical or laboratory evidence of HIV infection, discontinue PEP and transition to selected PrEP medication option: see next section for individualized decision-making regarding medication selection.
• Transition to the recommended HIV testing schedule as outlined in CDC’s PrEP Guidelines; testing schedules differ by PrEP medication used. Additional/more frequent HIV testing may be considered if there is clinical concern for HIV acquisition in the setting of recent PEP/PrEP use: for example, some PrEP experts recommend a repeat HIV test after the first month of PrEP use in persons who transitioned from PEP to PrEP.
Baseline and Follow-up Laboratory Testing
See discussion of rationale for additional details.
Oral PrEP: TDF/FTC or TAF/FTC
| Baseline1 | Every 3 months | Every 6 months | Annually | |
|---|---|---|---|---|
| HIV Ag/Ab | ✓ | ✓ 2 | – | – |
| HIV-1 RNA | +/- 3 | +/- 3 | – | – |
| Serum creatinine for estimated CrCl (eCrCl) | ✓ | – | If age > 50 years, baseline eCrCl < 90 mL/min, or other risk factors for renal disease | ✓ |
| HBsAg, HBcAb, HBsAb | ✓ | – | – | – |
| Syphilis, GC/CT (site-directed) | ✓ | ✓ 4 | ✓ 4 | – |
| HCV Ab w/ reflex to RNA if reactive | ✓ | – | – | If ongoing exposures5 |
| Lipid panel (if on TAF/FTC and age > 50 years or risks for CVD)6 | ✓ | – | – | ✓ |
1 At minimum, normal renal function should be confirmed and hepatitis B status should be ascertained, and negative HIV testing [with at least an Ag/Ab assay] should be documented within 7 days of oral PrEP initiation. Other listed baseline tests are recommended but not required prior to prescribing oral PrEP: this may be particularly relevant for “low barrier” PrEP care settings and/or settings with limited laboratory testing resources.
2 Some PrEP experts also recommend early repeat HIV testing, i.e., after the first month of PrEP use.
3 2021 CDC PrEP Guidelines recommend qualitative or quantitative HIV-1 RNA testing if any oral PrEP or PEP medications have been taken within the preceding 3 months or if a cabotegravir injection has been received within the preceding 12 months. RNA testing is also recommended if an exposure-prone event has occurred within the preceding 4 weeks with signs or symptoms of acute HIV within that period. Some clinicians opt to include RNA testing at baseline regardless of the presence of signs or symptoms of acute HIV.
4 STI and syphilis screening should be performed periodically; frequency should be informed by reported sexual exposures.
5 HCV screening should be repeated in individuals without chronic HCV infection who have ongoing exposures. For people with previously treated HCV infection, screen with HCV RNA (i.e., not HCV Ab).
6 2021 CDC PrEP Guidelines suggest baseline and annual lipid monitoring for all people taking TAF/FTC due to the association between TAF exposure and lipid abnormalities/weight gain; however, the clinical significance of these observations remains uncertain, particularly in young people without other risk factors for CVD.
Injectable PrEP: Cabotegravir
| Baseline1 | 4 weeks | Every 2 months | Every 4-6 months | Annually | |
|---|---|---|---|---|---|
| HIV Ag/Ab | ✓ | ✓ | ✓ | – | – |
| HIV-1 RNA | ✓ | ✓ | ✓ | – | – |
| HBsAg, HBcAb, HBsAb | ✓ | – | – | – | – |
| Syphilis, GC/CT (site-directed) | ✓ | – | – | ✓ 2 | – |
| HCV Ab w/ reflex to RNA if reactive | ✓ | – | – | – | If ongoing exposures3 |
2 STI and syphilis screening should be performed periodically; frequency should be informed by reported sexual exposures.
3 HCV screening should be repeated in individuals without chronic HCV infection who have ongoing exposures. For people with previously treated HCV infection, screen with HCV RNA (i.e., not HCV Ab).
Why are these specific labs recommended?
• HIV Ag/Ab: Because the risk of HIV drug resistance development is relatively high when someone inadvertently starts PrEP in the setting of unrecognized/undetected HIV infection, HIV testing should be performed at baseline, and PrEP should be initiated (i.e., first dose taken) within 7 days after a negative test. Instrumented, laboratory-based assays are preferred, but use of a “rapid” (i.e., point-of-care) FDA-approved, fingerstick blood test is an option. Rapid oral HIV tests are less sensitive and therefore not recommended.
• HIV-1 RNA: A negative HIV Ag/Ab or Ab-only test with detectable HIV RNA results may indicate recent HIV acquisition. Providers should inquire about exposures within the last few months and evaluate for signs/symptoms of acute HIV – consider reaching out to a local HIV expert and/or the NCCC PrEPline or NCCC HIV Warmline for questions regarding HIV test interpretation and PrEP. Note: testing should also be considered when clinically indicated, such as in the setting of missed doses with concerning signs or symptoms.
• Serum creatinine: Renal function should be assessed prior to and during oral PrEP use, given the association between tenofovir (particularly tenofovir disoproxil fumarate) exposure and nephrotoxicity. Although tenofovir-associated nephrotoxicity is generally uncommon, renal function monitoring is recommended especially in persons who may have elevated risk for kidney disease.
• Hepatitis B: Testing (with hepatitis B surface antigen [HBsAg], core antibody [HBcAb], and surface antibody [HBsAb]) is recommended at baseline especially for people initiating oral PrEP, because oral PrEP medications also have anti-HBV activity. At minimum, negative HBsAg status should be confirmed and people who are HBV susceptible should be offered vaccination. Note: a reactive HBsAg is not a contraindication to starting daily oral PrEP; however, patients should be further evaluated for HBV treatment eligibility and counseled on the possible need for clinical and laboratory monitoring when/if daily oral PrEP is discontinued (see Section on HBV, HCV, and other STIs for details). 2-1-1 oral PrEP for people with reactive HBsAg is not recommended due to concerns regarding intermittent (i.e., non-daily) medication exposure in the setting of chronic HBV infection.
• Sexually transmitted infection (STI) screening for syphilis, gonorrhea, and chlamydia: PrEP care presents a unique opportunity to screen for and treat STIs. For most persons on PrEP, STI screening every 3-6 months is recommended but may be performed more or less frequently depending on symptoms and reported behaviors/exposures. GC/CT testing should be performed at all reported sites of potential exposure (oral, genital, rectal); patient self-swabbing is acceptable.
• Hepatitis C: PrEP care also presents an opportunity to screen for hepatitis C, which can be transmitted sexually and through injection drug use. Reactive HCV antibody results should be followed by HCV RNA (“viral load”) testing to confirm active infection. Persons without chronic HCV infection who have ongoing risk for hepatitis C exposures should be re-screened annually. People with previously treated HCV infection should be re-screened with HCV RNA (i.e., not HCV Ab, which often remains reactive after HCV treatment): more information is available via the American Association for the Study of Liver Diseases HCV Guidelines.
• Pregnancy testing: Testing is generally recommended at baseline for persons of pregnancy potential, to guide additional information sharing and counseling. PrEP medications are not contraindicated during pregnancy; however, an informed decision-making process is advised when providing PrEP to persons who are or may become pregnant. For more information on PrEP in the context of pregnancy or breastfeeding, see Section on Pregnancy & Breastfeeding.
What are signs and symptoms of acute HIV?
Presentation of acute HIV infection is highly variable and many people experience no symptoms. Others experience a flu-like syndrome and may present with fever, headache, fatigue, myalgias/arthralgias, generalized rash, pharyngitis, lymphadenopathy, night sweats, and/or diarrhea. Observations from clinical trials suggest that clinical presentation of “classic” acute retroviral syndrome is almost always absent among people on PrEP (especially people on LA-CAB) who subsequently acquire HIV infection.
Clinical Monitoring: Side Effects and Toxicities
What are the most common side effects of oral PrEP medications?
Oral PrEP medications are generally safe and well tolerated. Initial “start-up” symptoms of nausea, flatulence, loose stools/diarrhea, headache, and fatigue are self-limiting and often resolve within the first month.
Are any major toxicities associated with oral TDF/FTC or TAF/FTC?
Toxicities are rare and typically do not require stopping oral PrEP; when they do occur, they usually resolve after medication discontinuation. TDF/FTC, for example, is associated with a small risk of kidney injury and bone mineral density loss, whereas TAF/FTC is associated with metabolic changes such as weight gain and increased triglyceride and cholesterol levels. For patients who have experienced toxicity attributed to oral PrEP use, consider reaching out to a local PrEP expert or the NCCC PrEPline to discuss further evaluation and management options.
Can oral PrEP medications cause liver function test (LFT) abnormalities?
Routine liver function testing/monitoring is not necessary for people on PrEP, since transaminase elevations were observed infrequently (<2%) in clinical trials. As with any concern for potential drug-induced liver injury, however, asymptomatic persons with LFT values < 3x ULN may be continued on medication with close monitoring. People with elevated LFTs should be evaluated as clinically indicated for possible hepatotoxin exposure (e.g., acetaminophen, alcohol, certain supplements) and/or other causes (e.g., viral hepatitis). In rare circumstances involving significant LFT abnormalities, and if no other explanation is identified, oral PrEP discontinuation may be considered in discussion with the patient.
What are the most common side effects from injectable PrEP (i.e., LA-CAB)?
Injection site reactions are the most commonly observed side effects: symptoms (pain/tenderness, swelling, redness/warmth) are typically mild to moderate, and decrease in severity over time. Symptoms can often be managed with supportive interventions such as over-the-counter analgesics and warm compresses. LA-CAB has also been associated with mild weight gain, the clinical significance of which is uncertain.
Are there any major toxicities associated with injectable PrEP (i.e., LA-CAB)?
While very uncommon, LA-CAB may cause hypersensitivity reactions including severe rash or rash with systemic symptoms, hepatotoxicity, and depression. LA-CAB should be discontinued immediately if a hypersensitivity reaction occurs. In cases of suspected hepatoxicity or depression, close clinical monitoring is recommended and decisions regarding medication continuation should be individualized.
HBV, HCV, and other Sexually Transmitted Infections
HIV PrEP does not prevent the acquisition of other STIs, therefore people receiving PrEP should undergo regular STI screening.
Can PrEP medications be prescribed to people with chronic HBV infection (i.e., reactive HBsAg)?
Chronic HBV infection is not a contraindication to oral daily or injectable PrEP. However, because TDF/FTC and TAF/FTC both have anti-HBV activity, people taking these medications who stop them have a small risk of experiencing a hepatitis flare—including a rare risk of fulminant hepatic failure. Patients with chronic HBV should be counseled to avoid oral PrEP discontinuation without first speaking with their provider and developing a plan for ongoing clinical and laboratory monitoring after medication discontinuation. On-demand PrEP (i.e., 2-1-1 dosing with TDF/FTC) is not recommended for persons with chronic HBV infection. For people receiving LA-CAB who have chronic HBV infection, evaluation for HBV treatment eligibility and monitoring is recommended.
Does PrEP prevent HBV infection?
Data indicate oral tenofovir-based PrEP may prevent or reduce the risk of incident HBV infection. However, vaccination is the preferred HBV prevention strategy for all HBV-susceptible adolescents and adults who are evaluated for PrEP.
Are there any special considerations related to PrEP use among people with chronic HCV?
HCV screening is indicated for most patients at initial PrEP evaluation, and patients with untreated HCV infection should be provided with information about the effectiveness and availability of HCV treatment (and linked to treatment services if possible). While none of the currently available PrEP medications have anti-HCV activity, all can be prescribed safely and concurrently with most HCV treatment regimens.
Are other ‘PrEP’ options available for other sexually transmitted infections (STIs)?
Currently, the use of antibiotics as pre-exposure prophylaxis for bacterial STIs is not recommended. However, recent data indicate that a single dose of doxycycline taken as post-exposure prophylaxis as soon as possible (preferably < 72 hours after sexual activity) significantly reduces acquisition of chlamydia, gonorrhea, and syphilis in MSM and transgender women. Additional information is provided by Centers for Disease Control and Prevention (CDC).
Pregnancy and Breastfeeding
Is it safe to take PrEP during pregnancy?
Yes. Observational data involving cisgender women on TDF/FTC have demonstrated a favorable safety profile, and no clinically significant maternal or fetal adverse outcomes have been noted. TAF/FTC is not currently recommended as PrEP for cisgender women (although data suggests it is generally safe for use in pregnancy), and there are limited data on LA-CAB in pregnancy. Providers are encouraged to submit case information to the Antiretroviral Pregnancy Registry, a voluntary, observational study evaluating outcomes of pregnancy exposures involving antiretroviral products (no patient identifiers are collected).
Is it safe to take PrEP while breastfeeding?
Yes. Although data are limited, studies involving cisgender women taking TDF/FTC as part of HIV treatment suggest limited amounts of these medications can be detected in breastmilk and breastfed infants; this is not expected to result in any adverse effects to a breastfed infant. TAF/FTC is not currently recommended as PrEP for cisgender women, and data are limited regarding LA-CAB and breastfeeding. Additional information available via the NIH LactMed® database.
Does the risk of HIV acquisition differ for people who are pregnant?
Susceptibility to HIV is greater during the periconception, antepartum, and postpartum periods. However, if taken as prescribed, daily oral TDF/FTC is anticipated to be an effective HIV prevention option for pregnant persons.
Are there different monitoring recommendations for pregnant or breastfeeding people on PrEP?
In general, no. Pregnant people taking oral PrEP should be tested for HIV every three months, or at least once per trimester. More frequent HIV testing during pregnancy/breastfeeding could be considered on an individual basis. For questions regarding testing of infants born to persons taking PrEP, consider reaching out to a local PrEP expert or contacting the NCCC PrEPline or NCCC Perinatal HIV Hotline (24/7).
How frequently should pregnancy testing be offered for people on PrEP who may become pregnant?
Testing is generally recommended at baseline for persons of pregnancy potential, to guide additional information sharing and counseling at the time of PrEP initiation. Repeat pregnancy testing may be considered at PrEP follow-up visits, and should be tailored to an individual’s circumstances (testing may be particularly important for people on LA-CAB, given less data and experience with use of this medication in pregnancy).
Considerations for Specific Populations/Scenarios
Is PrEP an option for cisgender women?
Yes. Both TDF/FTC and LA-CAB are approved for use in cisgender women with potential sexual exposures, and TDF/FTC is also approved for cisgender women who inject drugs. Pharmacokinetic data suggest that due to differences in drug accumulation and half-life in cervicovaginal tissue (vs. rectal tissue), high levels of adherence to daily TDF/FTC may be especially important to support PrEP efficacy in cisgender women.
At this time, use of non-daily oral TDF/FTC (i.e., “2-1-1” or on-demand dosing) and daily TAF/FTC are not recommended for cisgender women due to lack of efficacy data.
Are there any special precautions when prescribing PrEP to transgender women?
TDF/FTC, TAF/FTC, and LA-CAB are all FDA-approved for PrEP use in transgender women. There are no known or predicted clinically meaningful drug interactions between oral PrEP medications and feminizing hormones, such as estrogens and anti-androgen therapy (i.e., spironolactone). Currently there are limited data on the effect of LA-CAB on feminizing hormones, as well as PrEP efficacy with neovaginal exposures.
What about data for PrEP and transgender men and transmasculine individuals?
While safety and efficacy data are limited, available information suggests TDF/FTC should be effective for receptive front hole/vaginal exposures as well as receptive anal exposures. Currently there are no data on PrEP efficacy for transgender men engaging in insertive sex after phalloplasty. PrEP drug levels and testosterone levels do not meaningfully change among transgender men taking PrEP and exogenous testosterone concurrently.
Can PrEP be used in adolescents?
Yes, all currently available PrEP medications can be used in people < 18 years of age who weigh at least 77 lbs (35 kg) who have the same indications as for adults.
Important considerations for adolescents include medication/visit adherence and safety data (e.g., bone mineral density changes with TDF-based PrEP) as well as concerns regarding consent and confidentiality. The legal framework for prescribing PrEP to adolescents varies considerably by state, and providers should be familiar with local and state regulations.
Is PrEP appropriate for older adults?
There are limited data on PrEP use among older adults, however older age is not a contraindication. Careful clinical and laboratory monitoring (i.e., renal function testing, consideration of potential bone mineral density changes, attentiveness to possible side effects) may be prudent.
Are there any special considerations for people who use drugs?
Daily TDF/FTC is the only currently FDA-approved option for this indication, although 2021 CDC Guidelines endorse the use of LA-CAB for people who inject drugs if they also report sexual exposures. Concerns about medication/visit adherence should not preclude discussions about PrEP as an option for people who use drugs.
Can patients with end-stage renal disease (ESRD) be prescribed PrEP?
Although not studied specifically in these populations, LA-CAB efficacy and exposure are not expected to be significantly impacted by ESRD, and the CDC guidelines state that it can be considered for PrEP in people with CrCl < 30 mL/min, with increased monitoring for adverse effects. Oral PrEP options are potentially nephrotoxic as noted and have not been studied as PrEP in these populations, and their use as PrEP would therefore be considered off-label. Consider reaching out to a local PrEP expert or the NCCC PrEPline for guidance.
Other Miscellaneous FAQs
When and how is it safe to stop PrEP?
PrEP should be stopped if it is causing unacceptable side effects or toxicities, or if it is no longer indicated. For people experiencing challenges related to medication and/or visit adherence, consider asking what additional support or interventions may be helpful (prior to considering PrEP discontinuation). HIV testing should be performed at the time of PrEP discontinuation to ascertain status; for persons with reactive HBsAg, see previous section on PrEP and chronic HBV.
Because LA-CAB can remain at detectable serum levels for up to a year or more after the last injection, people with ongoing exposures who opt to discontinue LA-CAB should be offered oral PrEP to minimize the risk of developing HIV drug resistance should they acquire HIV infection during the LA-CAB “tail phase”.
Can PrEP medications affect HIV test results?
Yes. Antiretroviral exposure can impact viral replication dynamics and the body’s immune response to HIV infection, therefore standard screening algorithm results may be difficult to interpret. This phenomenon can occur with either oral or injectable PrEP, but appears to be more common with LA-CAB. Therefore, the CDC recommends co-testing with a standard HIV Ag/Ab assay and HIV RNA test to monitor for new HIV infection among people on PrEP.
What is the risk of emergent HIV drug resistance if someone acquires HIV while on PrEP?
With oral PrEP, most cases of drug resistance have occurred in people with undiagnosed HIV at the time of PrEP initiation. Rare cases of “breakthrough” infection with HIV drug resistance have been observed despite optimal dosing and adherence; this most commonly involves transmitted HIV drug resistance. For LA-CAB, while the likelihood of breakthrough HIV acquisition with on-time injections is extremely low, risk of emergent HIV drug resistance may be relatively high. This likely reflects ongoing – but waning – PrEP medication exposure after HIV infection is established (see above regarding LA-CAB “tail phase”).
Are there any major drug-drug interactions with PrEP medications?
While relatively uncommon, drug-drug interactions between both oral and injectable PrEP and other agents may occur. Before prescribing PrEP, a complete medication list should be ascertained and reviewed for potential drug interactions (various HIV-specific drug interaction resources are available, such as the University of Liverpool’s HIV drug interactions checker).