University of California, San Francisco |
This 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. Additionally, various CDC PrEP Clinical Practice Guidelines and Recommendations can be accessed here.
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, four medications are FDA-approved for PrEP: co-formulated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, Truvada®; generic also available), co-formulated tenofovir alafenamide/emtricitabine (TAF/FTC, Descovy®), injectable cabotegravir (LA-CAB, Apretude®), and injectable lenacapavir (LEN, Yeztugo®).
How effective is PrEP?
Like all medications, PrEP is most effective 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 and lenacapavir are both highly effective in preventing HIV. For all people 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 partners of unknown HIV status.
Universal, non-stigmatizing counseling messages and questions may be considered to raise patient awareness about PrEP and potentially enhance acceptance/uptake – 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 nPEP and PrEP?
Non-occupational post-exposure prophylaxis (nPEP) refers to preventive medications started soon (i.e., within 72 hours) after a recent potential HIV exposure. Non-occupational exposure scenarios include 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 nPEP 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 during the initial PrEP evaluation, offer screening/testing as indicated, and consider reaching out to a local PrEP/PEP expert or the NCCC for guidance on which test(s) to order, how to interpret recent test results (if available), and clinical management.
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 2021 PrEP Guidelines include information on transitioning from non-occupational PEP to PrEP. Generally, for people who will immediately transition from PEP 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; 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 (particularly for people who transitioned from PEP to PrEP). See summary tables below outlining recommendations for laboratory testing for people starting (or taking) PrEP.
Baseline and Follow-up Laboratory Testing
See discussion of rationale for additional details.
HIV Testing Schedule for People on PrEP
| Oral PrEP (TDF/FTC or TAF/FTC) | Cabotegravir | Lenacapavir | |
|---|---|---|---|
| Standard (instrumented) HIV Ag/Ab | Baseline1 and every 3 months thereafter | Baseline1 and every 2 months thereafter (to coincide with injections) | Baseline1 and every 6 months thereafter (to coincide with injections)2 |
| Additional testing with HIV-1 RNA (“viral load”)4 | Consider at baseline for people initiating PrEP if recent ARV (PEP or PrEP) use or exposure(s) of concern. Consider at continuation visits if significant gaps in adherence since last testing and/or exposure(s) of concern. | Baseline3 and every 2 months thereafter (to coincide with injections)3 | If newly initiating lenacapavir or missed doses of recent/prior PrEP regimen4 |
1 Guidelines also recommend retesting with HIV Ag/Ab one month after starting oral PrEP in certain scenarios (e.g. exposures close to time of PrEP initiation); at time of 2nd initiation dose of cabotegravir (e.g., one month after 1st dose); and one month after lenacapavir initiation if HIV RNA was not available/performed at baseline.
2 HIV Ag/Ab may be offered more frequently (e.g., every 3 months) as part of comprehensive STI screening in between lenacapavir doses.
3 Alternatively, a point of care (“rapid”) HIV test may be used in place of HIV-1 RNA for co-testing.
4 HIV-1 RNA should be drawn for anyone with signs or symptoms of acute HIV. In addition – although CDC recommends obtaining a sample for baseline HIV RNA testing for people initiating lenacapavir, providers should not delay the initial injection dose while awaiting RNA results if baseline HIV Ag/Ab is non-reactive.
Medication Monitoring and STI Screening Schedule for People on PrEP
| Baseline | Every 3-4 months | Every 6 months | Annually | |
|---|---|---|---|---|
| Serum creatinine for estimated CrCl (eCrCl) for oral PrEP only | ✓ | – | If age ≥ 50 years, baseline eCrCl < 90 mL/min, or other risk factors for kidney disease | ✓ |
| HBsAg, HBcAb, HBsAb, and HCV Ab (reflex to RNA if reactive) | ✓ | – | – | Reassess for HBV if non-immune with ongoing exposures; reassess for HCV if ongoing exposures |
| Syphilis, GC/CT (site-directed) | ✓ | ✓ | – | – |
Why are these specific labs recommended?
• HIV Ag/Ab: Because HIV drug resistance can develop relatively easily 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 (“viral load”) 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 for questions regarding HIV test interpretation for people starting or already taking PrEP. Note: HIV viral load testing should also be considered when clinically indicated, such as in the setting of missed PrEP doses in a person 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 nephrotoxicity is generally uncommon, renal function monitoring is recommended especially in persons who may have elevated risk for kidney disease.
• Hepatitis B: Testing (specifically “triple screening” 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 and clinical monitoring is recommended at/after discontinuation for people with hepatitis B infection. At a 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). Event-driven 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.
• Hepatitis C: Hepatitis C 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). Individualized provider consultation on HCV screening and treatment evaluation is available by calling the NCCC.
• Sexually transmitted infection (STI) screening for syphilis, gonorrhea, and chlamydia:
PrEP care presents an important opportunity for STI screening and treatment. For most persons on PrEP, screening is generally recommended every 3-6 months but may be performed more or less frequently depending on symptoms and history. GC/CT testing should be performed at all reported sites of potential exposure (oral, genital, rectal); self-swabbing is acceptable.
• Pregnancy testing: Testing is often offered at PrEP initiation to guide additional information sharing and counseling as relevant. Pregnancy is not a contraindication to PrEP use; however, an informed decision-making process is advised when providing PrEP to women 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 long-acting injectable cabotegravir) who subsequently acquire HIV infection.
Clinical Monitoring: Side Effects and Toxicities
What are the most common side effects of oral PrEP medications?
Oral PrEP is 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 oral TDF/FTC or TAF/FTC associated with any major toxicities?
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 individuals 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 who experience up to a 3-fold LFT increase from baseline after oral PrEP initiation 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 or LEN)?
Injection site reactions (ISRs) 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/cold compresses. LA-CAB has also been associated with mild weight gain, the clinical significance of which is uncertain.Development of nodules is a particular ISR noted with subcutaneous LEN. They tend to diminish in size during the initial dosing interval and become less noticeable with subsequent dosing cycles. Icing injection sites before and after medication administration may mitigate discomfort associated with LEN administration. Alternative injection sites (e.g., thigh) may be considered.
Are there any major toxicities associated with injectable PrEP (i.e., LA-CAB or LEN)?
While very uncommon, LA-CAB may cause hypersensitivity reactions including severe rash or rash with systemic symptoms, hepatotoxicity, and depressed mood. LA-CAB should be discontinued immediately if a hypersensitivity reaction occurs. In cases of suspected hepatoxicity or significant mood changes, close monitoring is recommended and decisions regarding medication continuation should be individualized.Inadvertent injection of LEN into dermal tissue has resulted in severe injection site reactions, including necrosis and ulcers. Proper injection technique targets subcutaneous tissue.
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 and vaccination when indicated. Additional preventive options such as doxyPEP may also be of benefit for some people on PrEP (see below).
Can PrEP 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. Event-driven oral PrEP (i.e., 2-1-1 dosing with TDF/FTC) is not recommended for persons with chronic HBV infection. For people receiving LA-CAB or LEN 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 for people with chronic HCV?
HCV screening is indicated for most patients at initial PrEP evaluation, and patients with untreated HCV infection should be provided 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 recommended 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, clinical trials data support the use of doxycycline taken as post-exposure prophylaxis as soon as possible (preferably < 72 hours) after sexual activity to reduce the likelihood of acquiring bacterial STIs such as chlamydia, gonorrhea, and/or syphilis. Information from the CDC is available here.
Pregnancy and Breastfeeding
Is it safe to take PrEP during pregnancy?
Yes. Observational data have demonstrated a favorable safety profile for TDF/FTC, and no clinically significant maternal or fetal adverse outcomes have been noted. The 2021 CDC guidelines do not recommend TAF/FTC as PrEP for receptive vaginal exposures due to limited efficacy data (however, other guidelines/practice recommendations state the medication can be used safely in pregnancy for other indications such as HIV and/or HBV infection). Trial data support the safety of LEN in pregnancy; although fewer data are available for LA-CAB, information to date suggests it can also be safely used 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. Studies involving lactating 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. Tenofovir alafenamide (TAF) results in lower milk levels and infant exposures than TDF. LEN can be detected at very low levels in breastfed infants. Data are more limited for LA-CAB; however, no significant adverse effects are expected for breastfed infants. Additional information is 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, oral PrEP, as well as LA-CAB and LEN, are all anticipated to be effective HIV prevention options in pregnancy.
Are there different monitoring recommendations for pregnant or breastfeeding women on PrEP?
In general, no. Pregnant women taking oral PrEP should be tested for HIV every three months, or at least once per trimester. People on LA-CAB generally undergo HIV testing every two months, and people on LEN generally undergo HIV testing at least every six months. Additional HIV testing during pregnancy/breastfeeding could be considered on an individual basis. For questions regarding the care of infants born to persons taking PrEP, consider reaching out to a local PrEP expert or contacting the NCCC’s PrEPline or Perinatal HIV Hotline (24/7).
How frequently should pregnancy screening be offered for people on PrEP who may become pregnant?
Screening is generally recommended at baseline PrEP evaluation for women who may be (or may become) pregnant, to guide additional information sharing and counseling at the time of PrEP initiation. Repeat pregnancy screening may be considered at PrEP follow-up visits, and should be tailored to an individual’s circumstances (for example, periodic assessment may be helpful for people on LA-CAB, given generally less data and experience with this medication in pregnancy).
Considerations for Specific Populations/Scenarios
Is PrEP an option for women?
Yes. TDF/FTC, LA-CAB, and LEN are all approved for use in women with potential vaginal sexual exposures, and TDF/FTC is also approved for everyone who inject drugs. Although early pharmacokinetic data suggested differences in drug accumulation and half-life in cervicovaginal (versus rectal) tissue which might require higher levels of adherence to oral PrEP for women, newer modeling analyses are re-examining this to help inform updated clinical guidelines and best practices.The 2021 CDC guidelines do not recommend use of non-daily (i.e., event-driven) oral TDF/FTC or daily TAF/FTC for women due to limited data from initial clinical trials. However, based on newer data, updated guidance from other organizations (e.g., 2024 IAS-USA guidelines panel) includes recommendations on when TAF/FTC might be considered for vaginal exposures. It is also important to note there are no known or predicted clinically meaningful drug interactions between oral PrEP medications and hormones, such as estrogens or testosterone, or anti-androgen therapy (i.e., spironolactone).
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) and 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 relevant local/state regulations.
Is PrEP appropriate for older adults?
There are limited data specifically examining PrEP use among older adults, however older age is not a contraindication. Careful clinical and laboratory monitoring (i.e., attentiveness to potential side effects including bone mineral density changes, renal function testing) 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. 2025 CDC recommendations offer lenacapavir as another option in persons (weighing at least 77 lbs) who would benefit from PrEP: although efficacy data for persons who inject drugs have not yet been published, clinical trials are underway. 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?
None of the currently FDA-approved options have been specifically studied as PrEP among patients with end-stage renal disease on hemodialysis or peritoneal dialysis, therefore PrEP use in these populations would be considered off-label. Consider reaching out to a local PrEP expert or the 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 or desired. 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 and LEN 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 or LEN should be offered oral PrEP to minimize the risk of developing HIV drug resistance should they acquire HIV infection during the “tail phase”. Follow-up testing after medication discontinuation should also be discussed.
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 most common with LA-CAB. The 2021 CDC guidelines recommend co-testing with a standard HIV Ag/Ab assay and HIV RNA test to monitor for new HIV infections among people on PrEP. Other guidelines differ in their recommendations for laboratory monitoring. Providers seeking individualized support to review and implement testing recommendations are welcome to call the NCCC PrEPline.
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 oral medication dosing and adherence; this most commonly involves transmitted HIV drug resistance. For LA-CAB and LEN, 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 may reflect suboptimal medication levels and other factors; studies are ongoing to better understand why and how breakthrough infections and emergent drug resistance occur among people using long-acting injectable PrEP.
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. In some cases, it may be helpful to review potential drug interactions involving specific medication combinations with an experienced clinical pharmacist or utilize specially designed tools that can provide detailed information on various PrEP medications.Of note, lenacapavir (LEN) is a substrate of CYP3A, P-gp and UGT1A1. Therefore, co-administration with strong inducers may necessitate supplemental LEN dosing: see Tables 4 and 5 of current package labeling. LEN is also a moderate inhibitor of CYP3A and P-gp, and therefore co-administration may increase the concentrations of these CYP3A and P-gp substrates, resulting in increased risk of adverse events.
How should partial doses (e.g., incomplete injections, leakage) of long-acting injectable PrEP be prevented, assessed, and/or managed?
This is an area of emerging interest and extremely limited data; best clinical practices are evolving based on real-world implementation experiences.
Dosing deviations were uncommon in clinical studies of injectable cabotegravir: this includes studies of both cabotegravir/rilpivirine as well as LA-CAB as PrEP. Pharmacokinetic modeling analyses suggest that corrective dosing (or covering with an alternative PrEP option) may need to be considered for lower than planned cabotegravir doses.
During initial lenacapavir PrEP trials, mild-to-moderate amounts of leakage (e.g., fluid is absorbable with a bandage and/or small 2×2 gauze pad) were not thought to contribute significantly to changes in plasma concentrations. Rarely, for cases of more significant leakage (e.g., fluid soaked through [bandage], 2×2 gauze, and also clothing), investigators transitioned to alternative PrEP using oral medications. The lenacapavir manufacturer currently recommends that providers use clinical judgment to determine the need for additional PrEP coverage based on the amount of leakage: specifically, if the amount of leakage requires more than 1-2 bandages and 1-2 small (2×2) gauze pads for absorption, additional coverage may need to be considered. Consider reaching out to a local PrEP expert and/or NCCC’s PrEPline to discuss specific cases.
Anticipatory counseling should be provided to patients, and proper injection technique and aftercare should be followed. Consider advising patients to avoid exercise or strenuous physical activity for a few hours after medication administration, and not to manipulate the injection area. Early follow-up (e.g., telephone outreach) after dose administration may be helpful to ensure patients are screened for injection site reactions and leakage events in a timely fashion.
