INTRODUCTION — Up to two million new HIV infections occur yearly worldwide. As there is no effective vaccine to prevent HIV transmission, behavioral and biomedical HIV prevention strategies are needed to reduce HIV acquisition [1-3]. For HIV-uninfected patients, pre-exposure prophylaxis (PrEP) using antiretroviral medications is an evidence-based way to prevent new infections among those at greatest risk.
This topic will review how to administer PrEP to appropriate candidates. A discussion of how to assess patients for PrEP and other strategies to prevent HIV infection (eg, the use of antiretroviral therapy for HIV-infected patients, postexposure prophylaxis for HIV-uninfected patients, and male circumcision) are discussed elsewhere. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis" and "HIV infection: Risk factors and prevention strategies" and "Management of nonoccupational exposures to HIV and hepatitis B and C in adults" and "Management of health care personnel exposed to HIV".)
ASSESSING PATIENTS FOR PrEP — To determine who should receive pre-exposure prophylaxis (PrEP), clinicians should assess the potential benefits and risks of therapy (table 1). Among those who are adherent, PrEP can reduce the risk of HIV transmission by greater than 90 percent, although rare infections may still occur [4-7].
The initial evaluation of a patient who is interested in initiating PrEP is summarized below and described in detail elsewhere:
●Clinicians should obtain a detailed sexual and drug use history to determine if the patient is at high risk of HIV acquisition, and therefore likely to benefit from PrEP. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Assessing risk of HIV acquisition'.)
●The patient should then be evaluated for the presence or absence of conditions that could put them at risk of developing adverse outcomes related to PrEP (eg, acute HIV, reduced kidney function, active hepatitis B virus [HBV] infection, osteoporosis). (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Assessing risk of treatment'.)
●Clinicians should also determine if the patient has potential barriers that would prevent them from adhering to the medication regimen. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Assessing willingness to adhere to PrEP'.)
In general, we offer PrEP to most patients without HIV who are at high risk for HIV and are committed to daily medication adherence and close follow-up.
PrEP is generally not needed for patients who consistently engage in low-risk sexual behaviors (eg, consistent condom use when engaging in anal or vaginal intercourse, no mucosal exposure to genital secretions). Specific indications for PrEP, as well as considerations for certain populations (eg, patients with osteoporosis or HBV infection, pregnant persons), are described elsewhere. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Candidates for PrEP'.)
ORAL REGIMENS — Oral agents for pre-exposure prophylaxis (PrEP) to prevent HIV include the use of combination antiretroviral therapy (ART).
Patients receiving PrEP should be counseled about medication adherence and risk reduction strategies. In addition, patients should be monitored on a regular basis after PrEP has been initiated. (See 'Patient counseling' below and 'Patient monitoring' below.)
Available agents — The combination of tenofovir with emtricitabine has proven to be effective in reducing new HIV infections when used for PrEP. There are two formulations of tenofovir, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), and each is available as a coformulated tablet with emtricitabine.
●Tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) – For PrEP, once-daily TDF-FTC (tenofovir disoproxil fumarate 300 mg-emtricitabine 200 mg) is the most widely studied regimen among various populations, and it can reduce the risk of HIV transmission by close to 100 percent if taken as prescribed. Clinical trials have described only mild adverse effects (eg, nausea, diarrhea) compared with placebo, and these usually resolve during the first four weeks. However, there are concerns for renal and bone toxicity with long-term use. (See 'Efficacy of oral pre-exposure prophylaxis' below and "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Assessing risk of treatment'.)
●Tenofovir alafenamide-emtricitabine (TAF-FTC) – TAF has less bone and renal toxicity compared with TDF and, in the United States, is approved for PrEP in a coformulated tablet with FTC (tenofovir alafenamide 25 mg-emtricitabine 200 mg) [8]. However, TAF-FTC should not be used for those whose main risk for HIV is receptive vaginal sex. Although there is much less experience with TAF compared with TDF, a multinational efficacy study comparing once-daily TAF-FTC with TDF-FTC in 5387 at-risk men who have sex with men (MSM) and transgender women found TAF-FTC to be noninferior to TDF-FTC in preventing HIV infection (HIV incidence of 0.16 per 100 person-years versus 0.34 per 100 person-years, respectively) [7]. TAF-FTC had better bone and renal biomarker safety outcomes but was associated with mild weight gain and dyslipidemia, although the magnitude of the differences were small for all of these outcomes, and the duration of follow-up was modest.
Discussions of injectable therapy and experimental agents are found below. (See 'Long-acting injectable cabotegravir' below and 'Investigational approaches' below.)
Preferred PrEP regimen for most individuals — For most adults and adolescents, we suggest TDF-FTC rather than TAF-FTC. We give TDF-FTC once daily for as long as the risk of infection persists. In adolescents, tenofovir (both TDF and TAF) plus emtricitabine should only be used in patients who weigh at least 35 kg. Discussions of duration of therapy and alternative dosing regimens are found below. (See 'Duration of pre-exposure prophylaxis' below and 'Alternatives to daily oral therapy' below.)
We generally prefer TDF-FTC rather than TAF-FTC for PrEP initiation because of the extensive experience with the use of this agent. In addition, TAF-FTC has been associated with mild but greater weight gain and slight changes in lipid parameters that are less favorable compared with TDF-FTC [9]. However, in certain MSM and transgender women with bone and renal issues who are not eligible for TDF-FTC, TAF-FTC is preferred, as discussed below. (See 'For individuals with bone and renal safety issues' below.)
Some providers may prefer to administer TAF-FTC to adolescents, since such patients appear to be at higher risk for loss of bone mineral density during the growth phase of bone development, and in the randomized trial described above, TAF was not associated with reductions in bone density when used for PrEP [7]. However, we prefer TDF-FTC for most adolescents, since there are insufficient data to routinely use TAF-FTC in this population, and TAF-FTC has not been studied in patients <18 years of age. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Osteoporosis' and "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Adolescents'.)
For individuals with bone and renal safety issues
MSM and transgender women — For men who have sex with men (MSM) and transgender women who are at high risk for acquiring HIV, we suggest TAF-FTC (TAF 25 mg and FTC 200 mg once daily for the duration of the risk of HIV) rather than TDF-FTC for those who have:
●An estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 (calculator 1) – TDF has been associated with acute and chronic kidney disease in patients with HIV, and the safety of this agent has not been examined in patients without HIV who have an eGFR <60 mL/min/1.73 m2. By contrast, TAF-FTC is safe in those with an eGFR >30 mL/min/1.73 m2.
For patients with an eGFR >60 mL/min/1.73 m2 but with risk factors for renal disease, we try to balance the different risks of TDF and TAF. As an example, in patients who also have pre-existing obesity or dyslipidemia, we favor a trial of TDF-FTC with close monitoring for decreased renal function, since TAF-FTC has been associated with mild but greater weight gain and slight changes in lipid parameters compared with TDF [9]. Such patients should also be counseled on the importance of diet and exercise.
Neither TDF-FTC nor TAF-FTC should be used in those with an eGFR <30 mL/min/1.73 m2. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Renal function'.)
●Osteoporosis or risk factors for osteoporosis — TDF has been associated with reductions in bone density, whereas TAF-FTC was not associated with bone loss in the DISCOVER trial, a large trial comparing TAF-FTC with TDF-FTC for PrEP [7].
If TAF-FTC is being considered for adolescents with bone and renal issues, it should only be prescribed to those who weigh ≥35 kilograms.
Women and transgender men — For women and transgender men whose main risk for HIV is receptive vaginal sex, we generally avoid TAF-FTC. The DISCOVER trial, which compared TAF-FTC and TDF-FTC for PrEP, only evaluated those who engaged primarily in anal-receptive sex [7], and we feel the results cannot be generalized to those who engage in vaginal sex given the uncertainty of the clinical meaning of mucosal concentrations of TAF in vaginal fluids. Thus, our approach to PrEP depends upon concerns about using TDF. As examples:
●For patients with renal impairment (eGFR is <60 mL/min/1.73 m2) we typically defer PrEP. TDF-FTC is not recommended at this eGFR threshold.
●For those who have risk factors for renal disease but still have an eGFR ≥60 mL/min/1.73 m2, we suggest a trial of TDF-FTC with follow-up monitoring of renal function.
●For those with or at risk of osteoporosis, we determine whether to initiate PrEP with TDF-FTC on a case-by-case basis, weighing the risk of HIV with the potential risk of exacerbating bone disease.
Persons who inject drugs — For persons with kidney or bone disease whose risk factor for HIV is injection drug use, our approach depends upon the presence of other risk factors for HIV acquisition, since there are no studies evaluating the use TAF-FTC for PrEP in patients whose sole risk factor is injection drug use.
●In MSM and transgender women who have sexual risk in addition to injection risk, we administer TAF-FTC, similar to the approach described above. (See 'MSM and transgender women' above.)
●In patients who have injection drug use as their only risk factor, we think TAF-FTC is a reasonable alternative to TDF-FTC for those with an eGFR between 30 and 60 mL/min/1.73 m2 (calculator 1), since TAF achieves higher peripheral blood mononuclear cell concentrations than TDF and therefore may be effective for PrEP in the setting of injection drug use. For those with osteoporosis, we base the decision to use TAF versus TDF on the severity of bone disease, weighing the risk of potential bone loss with the uncertain efficacy of TAF-FTC.
●For those who have vaginal/frontal sex as a risk factor for HIV acquisition in addition to injection risk, the decision must be individualized, since the efficacy of TAF-FTC for PrEP has not been evaluated in injection drug users or those who engage primarily in vaginal sex. (See 'Women and transgender men' above.)
All persons who inject drugs should receive information on other risk reduction strategies in addition to PrEP. (See 'Drug use behaviors' below.)
Prescription quantity — We dispense PrEP as a 90-day supply, renewable only after HIV testing [10]. Prescribing a limited quantity of medication increases the likelihood that a patient will follow up for ongoing safety monitoring and adherence counseling. (See 'Patient monitoring' below.)
Patient counseling — When initiating PrEP, patients should be counseled about medication adherence and risk reduction strategies, as described below. Additional resources to help provide risk reduction counseling for patients receiving PrEP can be below. (See 'Additional resources' below.)
Medication adherence — Patients should be counseled regarding the importance of taking the medication as prescribed in order to achieve adequate drug concentrations. There is a clear association between adherence to the drug regimen and the efficacy of PrEP in decreasing HIV transmission [11-19]. (See 'Efficacy of oral pre-exposure prophylaxis' below.)
The relationship between adherence and PrEP efficacy has been found in all populations (eg, MSM, transgender women, heterosexual males and females). However, patients exclusively engaging in receptive anal sex may be able to miss an occasional dose and still be protected. In a trial that evaluated 1225 men who engaged in anal sex and received daily TDF-FTC, taking at least four doses per week was associated with a high level of protection [16]. By contrast, data suggest that six or seven doses per week are needed to protect patients who are exposed to HIV through vaginal intercourse [20,21]. This difference may be due to the high concentration of tenofovir achieved in rectal tissues, which is greater than that seen in cervicovaginal tissues [22,23].
Some patients may discontinue PrEP temporarily. It is important that clinicians educate patients to re-initiate PrEP before they begin to engage in high-risk behaviors [24]. When a patient wishes to resume PrEP, we repeat the same evaluation as in those who are initiating PrEP for the first time (table 1). (See 'Duration of pre-exposure prophylaxis' below.)
Condom use — Patients should be counseled to use condoms whenever possible (in addition to using PrEP) to reduce the risk of acquiring other sexually transmitted infections, and hepatitis C virus (HCV), as well as prevention of pregnancy [25-27]. In addition, rare cases of HIV transmission have occurred, even in the setting of appropriate PrEP medication adherence [5,28,29]. (See 'Patients with sexually transmitted infections' below and 'Transmitted drug resistance' below.)
However, some patients may choose not to use condoms. For such patients, we encourage condoms until PrEP achieves drug concentrations that protect against HIV. Based upon pharmacokinetic data for TDF [22,23,30], we advise condom use for:
●Seven days after starting PrEP for patients engaging in receptive anal sex
●Twenty-one days after starting PrEP for patients engaging in receptive vaginal sex
There is no formal guidance regarding timing of protection with TAF-FTC, so using the same parameters as TDF-FTC is reasonable.
When discussing the time from PrEP initiation to optimal protection, the clinician should assess the patient's desire for certainty. Our approach is consistent with the United States Centers for Disease Control and Prevention recommendations [10]. However, protection may be reached sooner, and other guidelines, including those of the World Health Organization, suggest that adequate tissue levels are achieved after seven days for both anal and vaginal sex [21,31,32]. The reason for the debate is based upon different interpretations of pharmacokinetic data, not on clinical trials. There are no clear data on the concentration of tenofovir in penile tissues, although it may be reasonable for men who only engage in insertive sex to use condoms for at least one week.
Drug use behaviors — Patients who inject drugs should be educated about safe injection practices and should also be given a referral to substance abuse treatment. Such patients remain at risk for acquiring other viral and bacterial infections (eg, HCV [25,26] and Staphylococcus aureus) that can be transmitted through unsafe injection practices. It is also important to educate patients about pharmacologic and behavioral treatments to reduce both injection and noninjection drug use. (See "Medication for opioid use disorder" and "Psychosocial interventions for opioid use disorder".)
Symptoms of acute HIV — Patients should be educated about the signs and symptoms of acute HIV infection (eg, lymphadenopathy, fever, malaise, and/or a maculopapular eruption). They should seek medical attention if such symptoms develop so they can be tested for HIV and initiate appropriate therapy if seroconversion occurred. (See "Acute and early HIV infection: Clinical manifestations and diagnosis" and 'Patients with newly diagnosed HIV infection' below.)
Risk of drug resistance — Among patients who become HIV infected while receiving PrEP, most are unlikely to develop drug-resistant virus [12-14,33]. In a meta-analysis that evaluated drug resistance in six clinical trials, drug resistance was identified in 6 of the 533 patients who became HIV infected after enrollment, and 8 of the 44 patients who had undiagnosed acute HIV infection at study entry [34]. If drug-resistant HIV is detected, it can be acquired (ie, the patient was infected with wild-type virus but develops resistance because they are taking PrEP), or it can be transmitted from their partner (the virus they were infected with already had drug resistance mutations).
Detailed discussions of the evaluation and management of patients with drug-resistant virus are found elsewhere. (See "Evaluation of the treatment-experienced patient failing HIV therapy" and "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy".)
Acquired drug resistance — In patients who develop drug-resistant virus while taking PrEP, the M184V (as well as the less common M184I) mutations are most likely to emerge since the genetic barrier to emtricitabine is low. By contrast, the genetic barrier to resistance is high for tenofovir, and, therefore, resistance to tenofovir (eg, K65R mutation) is less likely to occur. Exposure to study drug was believed to cause drug resistance in 4 of the 33 females in the Fem-PrEP trial and in 2 of the 51 patients in the Partners PrEP study [33,35]. Among those who developed resistance, the M184V emtricitabine resistance mutation was the most frequent. A more detailed discussion of HIV drug resistance mutations is found elsewhere. (See "Interpretation of HIV drug resistance testing".)
Transmitted drug resistance — Patients receiving PrEP may be infected with drug-resistant HIV. In two case reports, a patient became infected with HIV that contained drug resistance mutations for several classes of antiretroviral agents, including tenofovir and emtricitabine [5,6]. Transmission occurred despite tenofovir levels that were consistent with recent administration of the drug and long-term adherence. Thus, it is important to educate patients about the benefits of condom use in addition to PrEP. (See 'Patient counseling' above.)
No antiretrovirals besides tenofovir with emtricitabine have been proven to be effective when used for PrEP. Thus, if a patient has a known exposure to multidrug-resistant HIV, a postexposure prophylaxis regimen should be initiated that contains antiretrovirals active against the resistant virus. (See "Management of nonoccupational exposures to HIV and hepatitis B and C in adults".)
Alternatives to daily oral therapy — Some patients do not want to take daily oral therapy. Alternative dosing approaches may be an option for certain patients who can reliably predict when they will have condomless sex. However, on-demand dosing should not be used in patients with chronic hepatitis B virus infection.
If an alternative dosing regimen is being considered, it is important to inform patients that there is much less experience with these dosing regimens, and some have not been tested. In addition, patients may have difficulty remembering to take therapy that is not administered daily [36]. There are no data evaluating the use of alternative treatment regimens when TAF-FTC is used for PrEP, and there is no experience with alternative dosing in people who inject drugs.
The decision to administer an alternative dosing regimen, and the type of regimen, depend upon the patient's pattern of sexual activity. As examples:
●For patients who anticipate a discrete period of risk (eg, going on vacation), one option would be to start daily PrEP one week prior to the period when the patient is planning to have condomless sex for males, and three weeks prior for females, and continue PrEP for one month after. This approach is supported by pharmacokinetic data predicting protective levels of intracellular TDF and FTC [22]; it has not been completely evaluated in clinical trials. (See 'Preferred PrEP regimen for most individuals' above.)
●For patients who engage in condomless anal sex, another alternative would be on-demand (event-driven) therapy with TDF-FTC, in which a loading dose of TDF-FTC (two tablets) is taken 2 to 24 hours prior to sexual activity, one tablet is then taken daily while the patient is sexually active, and then continued for two more days after sexual activity has stopped. This specific regimen has been referred to as "2-1-1" PrEP. For patients who initiate event-driven therapy more than once within a week, the loading dose should be reduced to one tablet, instead of two [37]. Although this dosing strategy is not approved for use by the US Food and Drug Administration (which has only approved PrEP for daily use), the World Health Organization updated its guidance on PrEP in July 2019 to include the option of event-driven PrEP for MSM with the "2-1-1" dosing schedule [38]. However, this dosing regimen is not recommended in transgender women and heterosexual males and females since event PrEP data are limited in these other populations, and pharmacologic studies suggest the need for routine daily adherence in these populations [39,40]. The data supporting event-driven PrEP are discussed below. (See 'Men who have sex with men' below.)
Patient monitoring
Routine monitoring and counseling
Frequency — Patients receiving PrEP should have regular follow-up with a medical provider. We see patients one month and three months after starting treatment, and then every three months thereafter (table 2). We prescribe a three-month supply at each of the three-month visits. (See 'Preferred PrEP regimen for most individuals' above.)
More frequent follow-up may be necessary for patients who have been exposed to and/or have symptoms of a sexually transmitted infection (STI), as well as those with evidence of worsening kidney function. We also evaluate the need to continue PrEP (ie, ongoing risk behaviors) on an annual basis. (See 'Duration of pre-exposure prophylaxis' below.)
What to monitor — Every three months, we do the following (table 2):
●Perform HIV testing, preferably with a fourth-generation antigen/antibody test. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'HIV testing'.)
●Screen for symptoms of acute HIV infection. (See "Acute and early HIV infection: Clinical manifestations and diagnosis", section on 'Clinical features' and "Acute and early HIV infection: Treatment".)
●Perform routine screening for STIs (regardless of symptoms) among individuals with high-risk sexual behaviors (table 3). (See 'Patients with sexually transmitted infections' below.)
●Assess for medication adherence, risk behaviors, and side effects, and provide appropriate counseling.
●At the first three-month visit, we measure creatinine in all patients to assess for renal toxicity. After that, we monitor serum creatinine every three months in patients with risk factors for renal disease (eg, hypertension, diabetes, proteinuria, older age, prior history of renal insufficiency). (See 'Patients who develop renal abnormalities' below.)
●Perform a pregnancy test. (See 'Persons who become pregnant' below.)
Every six months, we evaluate the following (table 2):
●Serum creatinine in patients without risk factors for renal disease. (See 'Patients who develop renal abnormalities' below.)
●Urinalysis in patients with risk factors for kidney disease.
Hepatitis C virus (HCV) screening should be performed every 6 to 12 months in people who inject drugs and men who have sex with men (MSM) who engage in high-risk behaviors. Testing for viral hepatitis should be performed sooner if liver functions are elevated. More detailed guidance on HCV testing is presented elsewhere. (See "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Those with ongoing risk'.)
When PrEP was introduced, routine screening for HCV was not routinely recommended for MSM, since acute HCV was felt to occur primarily in MSM with HIV. However, emerging data suggest that MSM receiving PrEP are at increased risk for HCV acquisition [25-27,32,41-43]. As an example, in a cohort study of 350 MSM on daily or on-demand PrEP, the incidence of HCV was approximately 2.7 and 1.2 per 100 person-years, respectively [43]. Prior to the availability of PrEP, the reported incidence of HCV among MSM without HIV ranged from 0.04 to 0.13 per 100 person-years [44,45].
Counseling — In addition to monitoring, patients should receive ongoing counseling to optimize medication adherence and reduce high-risk sexual and drug-use behaviors while receiving PrEP:
●Adherence counseling includes educating patients about the importance of adherence, reviewing their medication dose and schedule, and identifying reminders and devices (ie, alarms) to minimize structural barriers. Additional considerations for adolescents are discussed elsewhere. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Adolescents'.)
●Risk reduction counseling involves understanding the patient's barriers and facilitators to increasing consistent condom use and/or reducing substance use, as well as identifying feasible steps towards risk reduction. Patients with social or mental health issues, such as untreated depression or active drug use, will need additional referrals and interventions to address their underlying comorbidities.
Additional resources for adherence and risk reduction counseling are found below. (See 'Additional resources' below.)
Subsequent management
Patients who develop renal abnormalities — The approach to patients who develop evidence of renal abnormalities depends upon the specific laboratory findings (eg, elevated creatinine, new proteinuria or glycosuria).
For patients using tenofovir disoproxil fumarate-emtricitabine (TDF-FTC), we discontinue it if:
●The estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2 (calculator 1). Most creatinine elevations resolve with treatment discontinuation [12,46,47].
In most patients with an eGFR >30 mL/min/1.73 m2, it is reasonable to replace TDF-FTC with tenofovir alafenamide-emtricitabine (TAF-FTC), which has been associated with fewer renal abnormalities when used as PrEP and has been approved for this indication [7]. (See 'For individuals with bone and renal safety issues' above.)
●There is evidence of moderate or severe proximal tubular dysfunction or Fanconi syndrome (eg, hypophosphatemia due to hyperphosphaturia, renal glycosuria, hypouricemia, and/or aminoaciduria). In such patients, TAF-FTC should not be used. (See "Etiology and diagnosis of distal (type 1) and proximal (type 2) renal tubular acidosis", section on 'Proximal (type 2) RTA'.)
For patients whose eGFR declines significantly on TDF-FTC (eg, a 20 percent decrease) but remains above 60 mL/min/1.73 m2 and for those who develop new mild proteinuria without additional evidence of proximal tube dysfunction, TAF-FTC is a reasonable alternative. These patients should also be evaluated for other causes of renal disease, if possible in consultation with a specialist. If no alternative etiology is identified, the modest renal abnormalities persist, and TAF-FTC is not an option, the decision to continue TDF-FTC and risk developing worsening kidney function must be weighed against the decision to discontinue PrEP altogether and risk HIV transmission. (See "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting" and "Urinalysis in the diagnosis of kidney disease".)
Persons who become pregnant — For persons who become pregnant, the risk of acquiring HIV must be weighed against the risk of using antiviral medications during pregnancy and the limited, albeit increasing, data on the efficacy of PrEP during pregnancy. More detailed discussions of the use antiretroviral agents in pregnancy are found elsewhere. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Pregnancy' and "Safety and dosing of antiretroviral medications in pregnancy".)
Patients with sexually transmitted infections — Clinicians should perform STI testing every three months among individuals with high-risk sexual behaviors, even if they are asymptomatic. In one study, testing MSM for STIs every six months would have resulted in delayed diagnosis and treatment for a substantial proportion of asymptomatic STIs [48]. (See 'Routine monitoring and counseling' above.)
Many patients receiving PrEP continue to engage in high-risk sexual behaviors. In clinical trials and observational studies of MSM, approximately 30 to 50 percent of the men who receive PrEP were diagnosed with a bacterial STI [12,49-54].
Although some providers may be concerned that the use of PrEP increases high-risk behaviors, we continue PrEP in such patients since the risk of HIV transmission remains low despite the large number of STIs [49-51,55]. As an example, in one study that followed 657 men receiving PrEP, no new HIV infections occurred over approximately seven months of follow-up, even though approximately 30 percent were diagnosed with at least one STI [50].
Patients with or at risk for osteoporosis — The need for routine bone density screening prior to and after initiating PrEP is unclear, and we determine the need for monitoring on a case-by-case basis. Discussions of regimen selection in patients with or at risk for osteoporosis and the risk of osteoporosis in patients taking PrEP are presented elsewhere. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Osteoporosis'.)
Patients with newly diagnosed HIV infection — For patients diagnosed with new HIV infection, dual therapy with TDF-FTC or TAF-FTC should not be continued. For such patients:
●We obtain genotypic testing to assess for resistance. (See "Overview of HIV drug resistance testing assays", section on 'Genotypic resistance assays'.)
●Continue TDF-FTC or TAF-FTC (or change from TDF-FTC to TAF-FTC) and add a third agent with a high barrier to resistance such as dolutegravir or boosted darunavir [56]. We do not use a non-nucleoside reverse transcriptase inhibitor as the third agent, since the most common type of transmitted drug resistance is to this class. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach", section on 'Patients with transmitted drug resistance'.)
Most patients will suppress their HIV viral load on this regimen, even if there is resistance to tenofovir or emtricitabine (specifically, the M184V mutation). However, if the patient has multidrug resistance (eg, M184V and K65R), the regimen will need to be modified. Such patients should be managed with a provider experienced in managing drug-resistant virus. (See "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy".)
Cost considerations — Although PrEP may be cost effective in individuals at high risk for HIV acquisition, some patients are not able to reliably access PrEP since the cost of tenofovir-emtricitabine and required monitoring can be challenging if they have high copays, high deductibles, or are otherwise underinsured [57,58]. Many private and public insurers cover tenofovir-emtricitabine for this purpose; however, copayments and deductible costs vary widely. Gilead Sciences maintains a patient assistance program for PrEP, and several state health departments provide additional support for remaining costs. The "Ready, Set, PrEP" program from the United States Department of Health and Human Services also provides PrEP medications free of charge for those without insurance coverage for outpatient prescription medications: www.HIV.gov. Cost considerations may change after tenofovir disoproxil fumarate-emtricitabine becomes generic, and it may be substantially less expensive than tenofovir alafenamide-based regimens.
Efficacy of oral pre-exposure prophylaxis — PrEP has been associated with a reduction in HIV transmission in men who have sex with men (MSM) and transgender women who report high-risk sexual behaviors (eg, condomless anal sex), heterosexually active males and females who have sex with partners who are at high risk of HIV infection (eg, partners from areas where there is a high HIV prevalence), and in persons who injection drugs [34]. In a systematic review of randomized trials and observational studies with over 18,000 participants, PrEP was associated with reduced risk of HIV infection compared with placebo or no PrEP (2.37 versus 4.18 percent [risk ratio (RR) 0.46, 95% CI 0.33-0.66]) [59]. In six trials where adherence to PrEP was 70 percent or greater, the benefit was more pronounced (1.0 versus 4.1 percent [RR 0.27, 95% CI 0.19-0.39]).
Men who have sex with men — There have been several large trials demonstrating the efficacy of PrEP in reducing HIV transmission among MSM who are at high risk for HIV transmission. Reductions in HIV transmission have ranged from 44 to greater than 96 percent in post-hoc analyses, depending upon the level of adherence.
●Pre-Exposure Prophylaxis Initiative (iPrEx) – The iPrEx trial was a multinational trial where 2470 HIV-seronegative men and 29 individuals who identified as transgender women were randomly assigned to either tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) or placebo once daily [12]. All participants received HIV testing, risk reduction counseling, condoms, and management of sexually transmitted diseases at enrollment and throughout the trial. Participants were followed for a median of 1.2 years, and 100 patients became infected during follow-up (36 in the intervention arm and 64 in the placebo group), consistent with a 44 percent reduction in the incidence of HIV with TDF-FTC (95% CI 15-63). In a subgroup analysis, drug levels were found to correlate with a protective effect; drug was detected in 3 of 34 randomly selected subjects with newly acquired HIV infection (9 percent), compared with 22 of 43 participants who did not acquire HIV (51 percent).
A substudy of the iPrEx trial confirmed that those who acquired HIV infection were less likely to have detectable TDF or FTC levels in the serum or peripheral blood mononuclear cells within a month of infection, compared with those who did not become infected [11]. The protective efficacy of TDF-FTC increased to ≥96 percent for those whose drug levels suggested that they took at least four doses per week. These findings were supported in the 72-week open-label extension of the iPrEx trial that included 1603 HIV-uninfected individuals [16]. There were 4.7 infections per 100 person-years if levels indicated that no drug was taken, 2.3 infections per 100 person-years if drug concentrations suggested less than two tablets were taken per week, and 0.6 infections per 100 person-years if levels indicated that two to three tablets were taken each week. No infections occurred among those who were likely taking four or more tablets each week.
●Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD) – In an open-label randomized trial, 544 MSM received daily TDF (245 mg) and FTC (200 mg) either immediately or after a period of one year [49]. Three HIV infections occurred in the immediate group versus 20 in the deferred group (relative risk reduction 86 percent, 90% CI 64-96). There were no serious adverse events; however, 28 participants interrupted treatment secondary to nausea, headache, and/or arthralgia. This study was stopped early (after accrual of about 10 percent of projected enrollment) because of the high HIV incidence in the deferred therapy group (7.8 percent annually) and the significant reduction in HIV transmission in those on treatment.
●On-demand pre-exposure prophylaxis – The use of on-demand (event-driven) dosing was evaluated in a randomized trial of MSM who engage in condomless anal sex (IPERGAY) [37]. Patients received PrEP administered as a loading dose (two tablets of TDF-FTC) taken 2 to 24 hours prior to sexual activity, one tablet daily while the patient was sexually active, and then for two more days after sexual activity was stopped. Among the 400 men who were enrolled, 16 new infections occurred, 14 in those taking placebo, and 2 in those receiving on-demand TDF-FTC, consistent with an 86 percent reduction in HIV transmission (95% CI 40-98). In an open-label extension of this study that enrolled 361 patients who were followed for a median of 18 months, only one new HIV infection occurred in a patient who was not taking PrEP as prescribed [51].
Participants in the IPERGAY trial took an average of 15 pills per month, and the protection was comparable to that seen in men who were taking at least four doses per week in the open-label extension of the iPrEx trial described above [16]. In a post-hoc analysis, on-demand PrEP remained effective among the 269 patients who took ≤15 pills/month (median of 9.5) [60]; however, additional data are needed to confirm these findings since these patients were only followed for about six months.
In a subsequent interim analysis of an observational study in France, largely comprised of MSM, only two HIV infections were reported among 1500 study participants taking event-driven PrEP, and both had discontinued PrEP several weeks prior to infection [61].
●Tenofovir alafenamide-emtricitabine or tenofovir disoproxil fumarate-emtricitabine for PrEP (DISCOVER) study – In a randomized, double blind trial in North America and Europe of MSM engaging in condomless anal sex, daily tenofovir alafenamide-emtricitabine was noninferior to TDF-FTC [7]. (See 'For individuals with bone and renal safety issues' above.)
Transgender women — In a subsequent analysis of the iPrEx trial described above, 339 patients (14 percent) were classified as transgender women [12,62]. Compared with MSM, transgender women were more likely to report transactional sex, receptive anal intercourse without a condom, or more than five partners in the past three months [62]. There were similar numbers of new HIV infections in the group that received TDF-FTC and placebo (11 and 10, respectively); however, TDF was not detected in any of the patients who became HIV infected. In contrast, among the transgender women who had detectable levels of TDF, no HIV infections occurred.
Heterosexual men — Two large trials in Africa that included heterosexual men at high risk for sexual acquisition of HIV demonstrated that TDF-FTC can reduce the risk of HIV acquisition by approximately 80 percent compared with placebo.
●Partners-PrEP – The Partners-PrEP trial was a randomized trial conducted among 4758 discordant couples in Kenya and Uganda, which demonstrated that TDF (with or without emtricitabine) reduced the risk of HIV acquisition compared with placebo [13]. TDF and TDF-FTC use decreased the risk of HIV infection by 67 and 75 percent, respectively (17 and 13 infections compared with 52 infections in the placebo arm).
In this trial, over half of the patients were men. Among the male HIV-uninfected partners, the risk of infection was reduced 63 percent with TDF (9 of 984 men infected) and 84 percent with TDF-FTC (4 of 1010 infected) compared with placebo (24 of 959 infected) [13].
●TDF2 – In the TDF2 trial, which evaluated 1200 sexually active heterosexual females and males in Botswana, the rate of HIV infection was decreased by 62 percent (95% CI 21.5-83.4) among patients randomly assigned to daily TDF-FTC compared with placebo (1.2 versus 3.1 events per 100 person-years) [14]. A major limitation of this study was the high study noncompletion rate, which was approximately 33 percent in both arms.
Similar to the Partners-PrEP trial, in men, the TDF2 trial demonstrated a risk reduction in HIV infection of 80 percent with tenofovir-emtricitabine (2 of 331 men infected) compared with placebo (10 of 331 infected) [14].
Heterosexual females — Among at-risk heterosexual females, trials of PrEP to prevent HIV acquisition with both oral and topical formulations of antiretrovirals have yielded variable results. All of these trials have been conducted in resource-limited settings. Studies evaluating topical formulations are discussed above. (See 'Investigational approaches' below.)
Clinical trial data have raised questions about the efficacy of oral chemoprophylaxis for high-risk HIV-seronegative females who are sexually active. In some trials, TDF-FTC was found to have no effect on reducing transmission in females, whereas in others, transmission was reduced by approximately 70 percent.
The explanation for these disparate findings was major differences in medication adherence. As an example, an adherence-based meta-analysis model in females found that with adherence levels of at least 75 percent, oral PrEP is estimated to be effective (relative risk 0.39, 95% CI 0.25-0.60) [63]. The efficacy of PrEP may also be different in females compared with MSM because of relatively lower concentrations of tenofovir in the cervicovaginal tissue compared with colorectal tissue [30,64]. Other factors that may affect PrEP effectiveness in females are more controversial; for example, some have posited that hormonal contraception alters intracellular tenofovir levels, but others have not found this to be the case when evaluating clinical trial data [65].
The conflicting trial results are discussed below:
●Partners-PrEP – Among the female HIV-negative partners in the Partners-PrEP trial described above, the risk of HIV infection was decreased by 71 percent with TDF (8 of 595 females infected) and 66 percent with TDF-FTC (9 of 566 infected) compared with placebo (28 of 619 infected) [13]. The number of serious adverse events and pregnancies were similar among the three arms. Females who became pregnant had study medications discontinued; no pregnancy complications were observed.
●TDF2 – There was also a trend towards 50 percent fewer infections with TDF-FTC prophylaxis compared with placebo among the 557 females in the TDF2 trial of at-risk heterosexual individuals in Botswana. However, the difference was not statistically significant in this subpopulation because of the relatively small sample size and modest HIV incidence [14].
●FEM-PrEP – In contrast, the FEM-PrEP trial, a randomized-controlled clinical trial that was conducted among approximately 2000 sexually active African females, was halted when an interim assessment found no evidence of protective efficacy among those assigned to the TDF-FTC arm (4.7 compared with 5 infections per 100 person-years with placebo) [33,66]. In addition, females in the intervention arm had higher rates of pregnancy compared with those in the placebo arm, suggesting that they were engaging in more condomless intercourse. However, less than one quarter of the subset of FEM-PrEP participants who were assigned to receive TDF-FTC and underwent therapeutic drug monitoring had detectable plasma drug levels, suggesting a role of substantial nonadherence in the failure to demonstrate a protective effect [67].
●VOICE – Similar results were seen in another clinical trial (Vaginal and Oral Interventions to Control the Epidemic; VOICE trial), which was conducted among 5000 African females who were randomly assigned to oral tenofovir disoproxil fumarate alone, oral TDF-FTC, placebo pill, or tenofovir or placebo vaginal gel [17]. In this population of predominately young unmarried females with high HIV incidence, no study drug significantly reduced the risk of HIV acquisition. Tenofovir was detected in less than a third of blood samples from females, despite high levels of self-reported product use. A separate analysis suggested a protective effect among those that were adherent [68].
People who use injection drugs — In a double-blind trial in Thailand, 2413 HIV-seronegative males and females with a history of injection drug use during the previous year were randomly assigned to once-daily therapy with tenofovir or placebo [69]. All participants received HIV testing, individualized risk reduction, and adherence counseling; they were also offered condoms and methadone treatment. In addition, participants chose either daily directly observed treatment or monthly visits. The participants were followed for a mean of four years. The following results were reported:
●Fifty patients became infected during follow-up (17 in the intervention arm and 33 in the placebo group), which is consistent with a 49 percent reduction in the incidence of HIV with tenofovir (95% CI 9.6-72.2).
●Injection drug use, needle sharing, and high-risk sexual behaviors decreased in both arms.
●No tenofovir-associated resistance mutations were detected among those who seroconverted and had genotype testing.
A case-control analysis of those administered TDF evaluated whether drug levels correlated with a protective effect. Among those in the intervention arm, tenofovir was detected in 39 percent of the 13 HIV-positive participants and 67 percent of HIV-negative controls, which corresponds to a reduction in risk of HIV infection of 70 percent (95% CI 2.3-90.6) in participants with detectable concentrations of tenofovir. The protective benefits of PrEP were evident only after the first three years of follow-up, by which time there was a decrease in injection drug use and needle sharing. As such, it is not possible to make definitive conclusions about the efficacy of daily tenofovir on the prevention of parenteral transmission of HIV in isolation from a comprehensive prevention package and independent of its protective effect on decreasing sexual risk of HIV acquisition [70].
Effect on HSV-2 transmission — The use of PrEP with TDF decreased the risk of herpes simplex virus-2 (HSV-2) transmission, in addition to HIV transmission, in HIV serodiscordant heterosexuals [71,72]. As an example, among 1044 HSV-2- and HIV-negative participants who had HSV-2- and HIV-infected partners, TDF (with or without emtricitabine) significantly reduced the incidence of HSV-2 seroconversion (9.6 versus 14.0 percent) [71].
However, this benefit was not seen in MSM. In a subanalysis of the iPrEx trial described above, 1383 of 2499 participants (55 percent) were seronegative for HSV-2 at study entry [73]. Approximately 9 percent of participants acquired HSV-2. However, there was no difference in HSV-2 seroincidence among those receiving TDF-FTC compared with placebo (hazard ratio 1.1, 95% CI, 0.8-1.5).
LONG-ACTING INJECTABLE CABOTEGRAVIR — Long-acting cabotegravir (CAB LA), an injectable integrase inhibitor that is administered every eight weeks, was approved for use as PrEP in 2022. A randomized trial (HPTN 083) comparing CAB LA given every eight weeks with daily oral TDF-FTC in 4570 MSM and transgender women was stopped early since the study reached its efficacy endpoint, and there were fewer new infections in those who received CAB LA compared with TDF-FTC (13 versus 39) [74]. The safety of CAB LA was similar to that of TDF-FTC, except for injection site reactions leading to discontinuation, which occurred more frequently in those who received CAB LA versus placebo (2.4 percent versus none). Detailed information on the use of cabotegravir for PrEP can be found on the CDC website.
DURATION OF PRE-EXPOSURE PROPHYLAXIS — Patients should continue PrEP as long as the risk of infection with either main or nonmain partners persists. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Assessing risk of HIV acquisition'.)
For persons without HIV who have a sexual partner who has HIV:
●PrEP should be continued until the HIV-infected partner has achieved a stably suppressed viral load (eg, typically by six months after initiating antiretroviral therapy [ART]) [75,76]. Although the duration of ART required to suppress HIV in semen and cervical secretions is unclear, in a clinical trial of HIV-infected patients initiated on ART, there were no reports of HIV transmission when the HIV-infected patient was on ART and achieved suppression of their plasma viral load. A detailed discussion of the risk of HIV transmission among those receiving ART is presented separately. (See "HIV infection: Risk factors and prevention strategies", section on 'Treatment as prevention'.)
●Certain HIV-uninfected patients should continue PrEP even if their partner has been on ART. This includes those patients uninfected with HIV who are having condomless sex with other partners as well as those who have concerns that their partner infected with HIV is not taking their ART regimen as prescribed (and therefore at risk for virologic failure).
We typically continue oral PrEP for one month after the last high-risk exposure based upon experiences using post-exposure prophylaxis [22] (see "Management of nonoccupational exposures to HIV and hepatitis B and C in adults"). However, there are no data to guide this approach, and it is possible that a shorter duration of therapy after the last exposure would be sufficient [32]. HIV testing should be performed when PrEP is discontinued.
For patients with chronic hepatitis B virus (HBV) infection, the decision to switch to an alternative agent for HBV treatment after oral PrEP is discontinued, or to monitor for HBV flare, should be discussed with a provider experienced in the management of HBV; this is particularly important for patients with cirrhosis. (See "Hepatitis B virus: Overview of management".)
Special considerations for discontinuing PrEP in patients receiving injectable cabotegravir can be found on the CDC website.
If a patient wishes to resume PrEP, we repeat the same evaluation as in those who are initiating PrEP for the first time. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis".)
INVESTIGATIONAL APPROACHES
●Other antiretrovirals — Other long-acting antiretrovirals are in earlier stages of development, including the nucleoside transcription and translocation inhibitor, islatravir, which may be delivered orally or as a subcutaneous implant and has been found to be safe and well tolerated in humans [77].
●Alternative delivery systems — Topical formulations are not commercially available for PrEP. Although topical administration remains an attractive intervention because early studies suggested that it is safe and can achieve high drug concentrations in the genital mucosa [30], the results of randomized trials evaluating the efficacy of tenofovir vaginal gel have been conflicting. As an example, in one trial, tenofovir gel reduced HIV transmission by almost 40 percent (CAPRISA 004) [18]; however, the VOICE and FACTS 001 trial did not find protective benefit [17,19,78]. The reasons for the contrasting results from these studies are not fully understood. However, timing of tenofovir gel application relative to sex and nonadherence appeared to affect the efficacy [17-19,79]. Further work assessing the impact of the vaginal microbiome in degrading topical tenofovir is also underway [80]. For the time being, topical application of tenofovir gel is not recommended for any female population.
A vaginal ring using the non-nucleoside reverse transcriptase inhibitor has also been evaluated. In a randomized trial of 2629 females in Africa, they received a monthly vaginal ring containing dapivirine or placebo [81]. Among those assigned to dapivirine, the incidence of HIV infection was reduced by 27 percent (71 versus 97 infections; 95% CI 1-46). In addition, there was no difference in adverse events between the two groups. When data from sites with reduced retention and adherence were excluded, the incidence of HIV infection was reduced by 37 percent (95% CI 12-56). Findings from a separate study reported similar results [82]. However, data from subsequent analyses suggest that females who are highly adherent to the product have much greater levels of protection (eg, >70 percent) [83,84]. The dapivirine ring is now being evaluated in two open-label studies to assess real-world effectiveness, and preliminary data support a modest but important degree of efficacy [85,86]. In one open-labeled trial, 1456 females had access to the dapivirine vaginal ring [86]. Acceptance rates were high, and HIV incidence was 2.7 per 100 person-years compared with an expected incidence of 4.4 per 100 person-years. This ring is being evaluated for licensure by several international regulatory bodies.
Early phase studies of rectal microbicides and douches are underway given the frequent use of topical lubricants by individuals who engage in receptive anal intercourse.
●Other agents — Clinical trials are being conducted globally to examine other agents (eg, the broadly neutralizing antibody VRC01 and other longer-acting, more potent antibodies) [87-89]. A list of active PrEP studies can be found at the . However, until data are available, regimens other than TDF-FTC or TAF-FTC should not be used for PrEP, even if there is concern that a patient may be exposed to drug-resistant virus or if there is concern about suspected TDF/TAF- or FTC-related toxicity. (See 'Transmitted drug resistance' above.)
ADDITIONAL RESOURCES — Additional PrEP resources for patients and providers include:
●https://www.who.int/health-topics/hiv-aids#tab=tab_1
●https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf
●www.avac.org/prevention-option/prep
●www.aidsetc.org/topic/pre-exposure-prophylaxis
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: HIV prevention".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Taking medicines to prevent HIV before exposure (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Benefits of PrEP – Up to two million new HIV infections occur annually worldwide. Pre-exposure prophylaxis (PrEP) using antiretroviral medications can reduce the risk of HIV transmission by greater than 90 percent in patients who are at high risk for acquiring HIV, depending upon the level of adherence.
●Candidates for PrEP – To determine who should receive PrEP, clinicians should assess the potential benefits and risks of therapy (table 1). In general, we recommend PrEP for the following individuals (Grade 1A):
•Males and females who have a sexual partner with HIV and a detectable viral load
•High-risk men who have sex with men (MSM) and high-risk transgender women who have sex with men
•Heterosexual males who have condomless sex with female partners from areas of high general HIV prevalence (eg, sub-Saharan Africa)
We also suggest PrEP for other individuals at risk for HIV (eg, high-risk heterosexual men, heterosexual females with high prevalence of HIV in their sexual networks [eg, those from sub-Saharan Africa], and people who inject drugs) (Grade 2B). A detailed discussion of who should receive PrEP is presented in a separate topic review. (See "Patient evaluation and selection for HIV pre-exposure prophylaxis".)
●Oral PrEP regimens – The combination of tenofovir plus emtricitabine is effective in reducing new HIV infections when used for PrEP. There are two formulations of tenofovir, TDF and tenofovir alafenamide (TAF), and each is available as a coformulated tablet with emtricitabine (FTC).
•For most adolescents and adults, we suggest TDF-FTC rather than TAF-FTC (Grade 2C). There is much more experience with the use of TDF-FTC compared with TAF-FTC, and it is generally well tolerated. However TAF-FTC is the preferred choice for certain MSM and transgender women who might otherwise not be able to take PrEP (eg, those with bone and renal issues). (See 'Preferred PrEP regimen for most individuals' above and 'For individuals with bone and renal safety issues' above.)
•We suggest TDF-FTC be administered once daily for as long as the risk of infection persists (Grade 2C). Alternative dosing approaches, such as on-demand therapy, may be an option for certain patients who can reliably predict when they will have condomless sex, although there is less experience with these dosing regimens. (See 'Preferred PrEP regimen for most individuals' above and 'Duration of pre-exposure prophylaxis' above and 'Alternatives to daily oral therapy' above.)
●Long-acting injectable PrEP – Cabotegravir, an integrase inhibitor that is available in a long-acting injectable formulation (CAB LA), is also available for use as PrEP. (See 'Long-acting injectable cabotegravir' above.)
●Patient counseling – PrEP should be provided in conjunction with counseling on other risk reduction methods (eg, consistent condom use, safe needle practices) for maximal protection. (See 'Patient counseling' above.)
●Monitoring on treatment – Routine monitoring for adherence and safety is important for patients who use PrEP. This includes regular HIV antigen/antibody testing and comprehensive screening for sexually transmitted infections (STIs) (table 2). (See 'Patient monitoring' above.)
For persons taking oral PrEP, kidney function should also be monitored. We discontinue TDF-FTC in patients whose estimated glomerular filtration rate falls below 60 mL/min/1.73 m2 (calculator 1) or if there is evidence of Fanconi syndrome. In those patients whose glomerular filtration rate falls below 60 mL/min/1.73 m2 but remains above 30 mL/min/1.73 m2, switching TDF-FTC to TAF-FTC may be an option. (See 'Patients who develop renal abnormalities' above.)
ACKNOWLEDGMENT — We are saddened by the death of John G Bartlett, MD, who passed away in January 2021. UpToDate gratefully acknowledges Dr. Bartlett's role as section editor on this topic, his tenure as the founding Editor-in-Chief for UpToDate in Infectious Diseases, and his dedicated and longstanding involvement with the UpToDate program.
