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 identify candidates for PrEP. A discussion of antiviral therapy for PrEP, as well as other strategies to prevent HIV infection (eg, antiretroviral therapy for HIV-infected patients, postexposure prophylaxis for HIV-uninfected patients, and male circumcision) are discussed elsewhere. (See "Administration of pre-exposure prophylaxis against HIV infection" 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".)
GENERAL APPROACH — For patients without HIV who are at high risk for acquiring HIV and are committed to medication adherence, PrEP is highly effective. Among those who are adherent, PrEP can reduce the risk of HIV transmission by greater than 90 percent [4], although rare infections may still occur [5-7]. (See 'Assessing willingness to adhere to PrEP' below.)
The main option for PrEP in all patients is tenofovir disoproxil fumarate-emtricitabine (TDF-FTC); for men who have sex with men (MSM) and transgender women at risk for sexual exposure to HIV, tenofovir-alafenamide-emtricitabine (TAF-FTC) is another option. Cabotegravir, an integrase inhibitor that is available in a long-acting injectable formulation (CAB LA), is also available for use as PrEP. (See "Administration of pre-exposure prophylaxis against HIV infection".)
To determine who should receive PrEP and which agent should be used, clinicians should assess the potential benefits and risks of therapy (table 1) [8-11]:
●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 'Assessing risk of HIV acquisition' below.)
●The patient should then be evaluated for the presence of conditions that could put them at risk of developing adverse outcomes related to PrEP (eg, reduced kidney function and osteoporosis with TDF-FTC; weight gain and dyslipidemia with TAF-FTC). Additional considerations for risk and benefit include the possibility of hepatitis B virus infection and pregnancy. (See 'Assessing risk of treatment' below.)
●Clinicians should also determine if the patient has potential barriers that would prevent them from adhering to a daily medication regimen. (See 'Assessing willingness to adhere to PrEP' below.)
The use of PrEP as an HIV prevention strategy has been modestly increasing in the United States since TDF-FTC was approved for PrEP in 2012 [12-14]. In one analysis, the annual number of PrEP users ranged from 8768 in 2012 to 100,282 in 2017 [15]. More recent data suggest that there were 132,340 PrEP users in the United States in 2018 [16]. Despite this reported increase, the number of individuals initiating PrEP represents a small fraction of the estimated 1.1 million people who have indications for PrEP in the United States [17,18]. Uptake has been particularly limited in populations at greatest risk for HIV infection (eg, African Americans) [14,19].
ASSESSING RISK OF HIV ACQUISITION — It is important for clinicians to obtain a detailed sexual and drug use history to assess a patient's risk for HIV acquisition [20]. The risk of HIV acquisition is based upon the type of exposure (table 2). A more detailed discussion of risk factors for HIV infection is found elsewhere. (See "HIV infection: Risk factors and prevention strategies", section on 'Risk factors for infection'.)
Sexual risk behaviors
Sexual history — To determine if a patient is at risk of acquiring HIV through sexual transmission, we recommend that clinicians assess sexual risk behaviors over the last six months. We obtain information regarding the patient's sexual behaviors, as well as the HIV status and the risk behaviors of the patient's sex partners. This includes:
●If the patient has had condomless penile-anal or penile-vaginal sex with partners other than their main partner
●If the patient is in a monogamous relationship, the HIV serostatus and viral suppression status of the partner
●If the patient has sex while using drugs
●If the patient has had any sexually transmitted infections (STIs) (see 'STI screening' below)
●The number of sexual partners
It is important that the clinician ask about the patient's sexual behaviors with both main and casual partners. Although some studies have reported a higher number of transmissions from casual partners, one study estimated that 68 percent of HIV transmissions among men who have sex with men (MSM) were from a main partner [21].
When discussing the level of risk, it is also important to understand the context of different social and situational factors. Clinicians and patients may make more informed decisions if an individual's patterns of behavior can be clarified. As an example, does the patient have discussions about HIV status with their partners or does the patient have anonymous partners of unknown HIV status?
Some providers may not feel comfortable talking a detailed sexual history; for such clinicians, several online resources (eg, the Fenway National Center for LGBT Health, the Ready, Set, Go guidelines, the CDC website) are available to help guide HIV risk assessment.
STI screening — Patients who are being considered for PrEP should be screened for common bacterial STIs. Although HIV risk behaviors, if elucidated, are likely to be reliable, some patients may not be comfortable disclosing sensitive information to providers. Thus, relying on self-reported risk alone may not be sufficient to make an informed decision about PrEP initiation, and other indicators of risk (eg, syphilis, anogenital gonorrhea, or chlamydia), which have been highly associated with HIV acquisition, must be considered.
STI screening should include serologic testing for syphilis, and nucleic acid amplification testing for gonorrhea and chlamydia at relevant mucosal sites (table 3). STI testing should be performed even in the absence of symptoms. A more detailed discussion of STI testing is found elsewhere. (See "Screening for sexually transmitted infections", section on 'Screening recommendations'.)
Screening for bacterial vaginosis and trichomonas is not routinely performed as part of the work-up before initiating PrEP, since these infections have not had as strong an association with HIV. However, their presence suggests that recent condomless sex has occurred, and this should lead the clinician to ask about numbers of partners and potential risks of partners.
Drug using behaviors — To assess a patient's risk for HIV acquisition through parenteral and other drug use, clinicians should ask about their drug use history over the last six months [22].
Factors associated with increased risk include:
●Injecting heroin, cocaine, or methamphetamine [23]
●Sharing needles or equipment
●Using nonparenteral drugs during sex (particularly methamphetamine), which may decrease the likelihood of using condoms [24]
ASSESSING RISK OF TREATMENT — To assess the potential risks of treatment with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC), providers should assess for previously undetected or acute HIV infection, reduced kidney function, chronic hepatitis B virus infection, osteoporosis, and pregnancy.
HIV testing — All patients should have plasma HIV testing prior to receiving PrEP to be certain that they do not have undiagnosed HIV infection [8,9]. HIV-infected patients should be treated with a combination antiretroviral regimen that typically consists of three antiretroviral agents, and the use of TDF-FTC or tenofovir-alafenamide-emtricitabine (TAF-FTC) for PrEP would put them at risk for developing drug-resistant virus. (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Risk of drug resistance'.)
The preferred HIV screening test is a fourth-generation antigen/antibody assay. A third-generation assay is acceptable if an antigen-antibody test is not available and the clinical history suggests that acute HIV infection is unlikely. However, rapid tests that use oral fluid should not be used [8]. A detailed discussion of HIV screening tests is found elsewhere. (See "Screening and diagnostic testing for HIV infection", section on 'Screening tests'.)
Additional testing for HIV RNA should be performed prior to initiating PrEP in the following groups of patients (regardless of which HIV antibody screening test is used):
●Those who describe signs or symptoms suggestive of acute HIV infection within the previous four weeks. Patients with acute HIV infection may present with a viral syndrome (eg, lymphadenopathy, fever, malaise, and/or a maculopapular eruption) and have a detectable HIV RNA in the absence of an HIV antibody and antigen in early cases. (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)
●Patients with an indeterminate antigen/antibody test. (See "Screening and diagnostic testing for HIV infection", section on 'Indeterminate test results'.)
●Patients who report a high-risk exposure (eg, recent sexual exposure to a partner with documented untreated HIV infection) within four weeks of starting PrEP, regardless of symptoms. In settings where access to prompt HIV RNA testing is not feasible, a fourth-generation HIV antigen-antibody testing can be used (earlier generation immunoassays are less sensitive).
Some providers believe that all patients should have HIV RNA testing performed one week prior to starting PrEP, regardless of their symptoms and/or exposure history. However, we do not use this approach, since the likelihood that patients with acute HIV infection will have a negative fourth generation test and a positive HIV RNA test is low in the absence of symptoms or recent exposures. In addition, HIV RNA testing is more expensive than testing with an antigen/antibody test.
The importance of HIV testing before PrEP was illustrated in the iPrEx trial [25] (see "Administration of pre-exposure prophylaxis against HIV infection", section on 'Men who have sex with men'). In this study, 410 of the almost 5000 subjects who were screened with rapid third generation tests were HIV infected. In addition, of the 110 participants who seroconverted during the study, 10 had a negative antibody test at baseline but were found to have a positive HIV RNA when testing was done on stored samples from enrollment. Five of these patients had symptoms consistent with acute infection, underscoring the significance of eliciting a full history prior to the initiation of PrEP, and testing for HIV RNA if symptoms are suggestive of acute infection. Most cases of HIV drug resistance occurred in patients with undiagnosed HIV at baseline. (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Risk of drug resistance'.)
Renal function — Serum creatinine should be measured prior to initiating PrEP. This informs the candidacy and/or selection of an agent for PrEP. Individuals with an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 are not candidates for PrEP with either TDF-FTC or TAF-FTC (calculator 1). Individuals with an eGFR <60 mL/min/1.73 m2 are not candidates for PrEP with TDF-FTC. The use of TDF versus TAF is discussed in detail elsewhere. (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Oral regimens'.)
For patients with an eGFR >60 mL/min/1.73 m2, but with risk factors for renal disease (eg, diabetes, hypertension, older age [eg, >40 years], nephrotoxic medications), we obtain a baseline urinalysis to assess for proteinuria and glycosuria. Although baseline urinalysis is not recommended by guideline panels, we find this information useful when monitoring such patients on PrEP (table 4). (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Patient monitoring'.)
Several clinical trials of PrEP have evaluated the risk of kidney injury with TDF-FTC [25-31]. In general, the risk of kidney injury is low in patients without HIV taking TDF-FTC. As examples:
●In a meta-analysis that included data from 10 randomized trials, there was an increased risk of creatinine elevations in patients who received TDF-based PrEP compared with placebo (odds ratio 1.36, 95% CI 1.09-1.71) [32]. However, of the 352 patients who experienced creatinine elevations, only 23 had increases that were greater than 1.3 times the upper limit of normal. Accordingly, in an additional meta-analysis that included data from 13 randomized trials, there was no difference in serious, grade 3 creatinine elevations among participants receiving TDF-based PrEP versus placebo or no treatment (difference 0 percent, 95% CI 0-0) [33].
●In a subgroup analysis from a randomized trial of 1549 patients, there was no increased risk of tubulopathy over 24 months among those who did and did not receive TDF-FTC (1.7 versus 1.3 percent, respectively) [31]. However, one patient who received TDF-FTC developed Fanconi syndrome while taking concurrent nephrotoxic medications. (See "Etiology and diagnosis of distal (type 1) and proximal (type 2) renal tubular acidosis".)
Certain risk factors have been associated with declines in renal function, such as baseline eGFR <90 mL/min/1.73 m2 and age greater than 40 [34]. In addition, higher tenofovir concentrations have been associated with reduction in kidney function; however, there is insufficient evidence to incorporate therapeutic drug level monitoring into routine care.
Renal effects appear to be even less frequent with TAF-FTC than TDF-FTC. In a randomized, non-inferiority study of 5387 men who have sex with men (MSM) or transgender women (the DISCOVER study), use of TAF-FTC as PrEP was associated with small but statistically significant differences in eGFR at 96 weeks when compared with TDF-FTC PrEP [35]. Renal adverse events were rare with both TAF-FTC and TDF-FTC, with only 13 patients discontinuing study drug due to renal adverse events (5 TAF-FTC and 8 TDF-FTC).
Hepatitis B and C infection — Patients who are considering PrEP should have baseline testing for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.
●Hepatitis B infection – Patients should be evaluated for the presence of HBV infection prior to initiating PrEP. This includes testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs). (See "Hepatitis B virus: Screening and diagnosis".)
•Patients without evidence of prior infection (ie, anti-HBs-, anti-HBc-, HBsAg-negative) should be vaccinated against HBV since individuals who engage in high-risk sexual and drug-use behaviors are at increased risk for acquiring hepatitis B. (See "Hepatitis B virus immunization in adults" and "Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Transmission of HBV'.)
•Patients with resolved HBV (anti-HBs- and anti-HBc-positive) do not require vaccination, and no additional monitoring is needed if PrEP is initiated.
•Patients with evidence of chronic HBV infection (ie, HBsAg-positive) can still receive PrEP; however, special considerations include:
-For patients who require antiviral therapy for HBV, TDF, and TAF are considered first-line treatments. Thus, TDF or TAF can be used as part of a PrEP regimen and can also be used to treat chronic HBV. (See "Hepatitis B virus: Overview of management", section on 'Antiviral therapy'.)
-In patients with chronic HBV who do not require treatment, the decision to use PrEP with TDF-FTC or TAF-FTC should be based primarily on the risks, benefits, and patient preferences for using PrEP as an HIV prevention strategy. If such patients choose to discontinue TDF-FTC or TAF-FTC (eg, secondary to cost or side effects, or if PrEP is no longer needed), there is a theoretical risk that discontinuing therapy may result in a flare of their HBV [8,9]. Although data from the iPrEx trial did not demonstrate a flare in the six HBsAg-positive patients who discontinued TDF-FTC [36], additional data will be helpful in determining the relative risks and benefits of PrEP in this group of patients. A discussion of patient monitoring after discontinuing PrEP is found elsewhere. (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Patient monitoring'.)
•Some patients may only be positive for anti-HBc. This could mean the patient has resolved (or is resolving) infection or low-level chronic infection; it could also be a false positive. The approach to PrEP must be determined on a case-by-case basis. Additional information on the evaluation of patients with isolated anti-HBc is found elsewhere. (See "Hepatitis B virus: Screening and diagnosis", section on 'Isolated anti-HBc'.)
●Hepatitis C infection — Persons who inject drugs and MSM who engage in high-risk sexual behaviors are at risk for HCV infection. Thus, such patients should be tested for HCV as part of the initial laboratory assessment. Patients who test positive should be referred for treatment. (See "Screening and diagnosis of chronic hepatitis C virus infection".)
It is important to note that certain agents used for the treatment of HCV (ledipasvir-sofosbuvir) may increase the level of TDF, and patients who are taking these agents should be monitored for TDF toxicity [8]. (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Patient monitoring'.)
Osteoporosis — Information should be obtained regarding a history of (or risk factors for) osteoporosis, since TDF has been associated with reductions in bone density. Bone loss appears to be greatest during the first six months, and then stabilizes after that [27,37]. The presence of osteopenia or osteoporosis informs our regimen selection for PreP; if only TDF-FTC is available, the risk of further bone loss must be balanced against the risk of acquiring HIV infection. Regimen selection for PrEP is discussed elsewhere (see "Administration of pre-exposure prophylaxis against HIV infection", section on 'Oral regimens'). The need for routine bone density screening prior to initiating PrEP is unclear. We obtain a baseline dual energy x-ray absorptiometry (DXA) scan in patients who have a history of osteoporosis if recent testing is not available, as well as those who are at high risk for osteoporosis. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men", section on 'Candidates for bone density testing' and "Evaluation and treatment of premenopausal osteoporosis", section on 'Screening'.)
Clinical trials of PrEP in adults found that patients without HIV who were assigned to TDF-FTC had greater declines in z-scores at the hip, lumbar spine, and forearm compared with those taking placebo; however, there were no differences in the rate of fractures [27,37]. As an example, in the iPrEx trial, 247 patients who received TDF-FTC and 251 who received placebo were evaluated with DXA scans every six months [37]. After 24 weeks, modest but significant declines in bone mineral density were seen in those who received TDF-FTC (spine: net difference -0.91 percent [95% CI -1.44 to -0.38 percent]; hip: -0.61 percent [95% CI, -0.96 to -0.27 percent]). There were only smaller further decreases in bone mineral density to week 96. A subsequent study found that bone loss normalized in most patients approximately six months after PrEP was discontinued [38]. In a study of adult MSM and transgender women, TAF-FTC was not associated with loss of bone mineral density when used as PrEP [35].
The bone loss seen with TDF may pose additional risks in adolescent MSM that have not been seen in adults [39,40]. Importantly, in adolescents, bone loss seems to occur before peak bone mass was attained. In a study that included 135 MSM, 18 to 22 years old, patients who took ≥4 doses per week of TDF-FTC had modest declines in bone mineral density, whereas those who took <4 doses of TDF-FTC had a 1.54 percent increase in spine bone mineral density [39].
There are no proven strategies to attenuate bone loss in patients taking PrEP. Vitamin D3 plus calcium supplementation was found to mitigate bone loss in patients with HIV taking a TDF-based antiretroviral therapy regimen [41]. Although, there are no data on the use of vitamin D to attenuate PrEP-related bone loss, measures to maintain adequate vitamin D levels could theoretically be helpful [42] and are being evaluated. (See "Overview of vitamin D".)
Pregnancy — Women of childbearing potential should have a pregnancy test prior to initiating PrEP. For those who are pregnant, the risk of acquiring HIV must be weighed against the risk of using antiviral medications during pregnancy and the limited data on the efficacy of PrEP during pregnancy.
In general, TDF and emtricitabine (both pregnancy category B drugs) are felt to be safe for use in pregnancy. However, there are concerns about fetal bone development associated with the use of TDF. TAF is not indicated for patients who engage in receptive vaginal sex and its safety during pregnancy is uncertain. A more detailed discussion of the risks of tenofovir during pregnancy is found elsewhere. (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Tenofovir'.)
In a post-hoc analysis of 288 pregnancies among African women enrolled in a PrEP efficacy trial, there were similar rates of pregnancy loss in those assigned TDF (with or without emtricitabine) and placebo (34 versus 32 percent) [43]. Although rates of preterm birth, congenital anomalies, and postnatal growth throughout the first year were also similar, PrEP was discontinued when pregnancy was detected; therefore, the effect of taking TDF with or without emtricitabine during the later stages of pregnancy was not assessed.
ASSESSING WILLINGNESS TO ADHERE TO PrEP — Potential barriers to adherence (eg, depression, active substance use, stigma) should be identified and addressed [44]. There is a clear association between the efficacy of pre-exposure prophylaxis (PrEP) in decreasing HIV transmission and adherence [4,25-27,45-49]. The relationship between adherence and PrEP efficacy has been found in all populations (eg, men who have sex with men, transgender women, heterosexual men and women). (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Efficacy of oral pre-exposure prophylaxis'.)
Additional information on assessing adherence and providing adherence counseling can be found in the in the US Public Health Services' practice guidelines and in a separate topic review. (See "Administration of pre-exposure prophylaxis against HIV infection".)
CANDIDATES FOR PrEP — In general, we offer pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) to patients without HIV who are at high risk for HIV, have normal kidney function, and are committed to daily medication adherence and close follow-up. We offer tenofovir alafenamide-emtricitabine (TAF-FTC) as an additional PrEP option for select patients who do not engage in receptive vaginal sex. PrEP is generally not needed for patients who consistently engage in low-risk behaviors (eg, consistent condom use when engaging in anal or vaginal intercourse, no mucosal exposure to genital secretions). Regimen selection for PrEP is discussed elsewhere. (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Oral regimens'.)
Special considerations for patients who have hepatitis B virus infection, osteoporosis, or who are pregnant are described above. (See 'Hepatitis B and C infection' above and 'Osteoporosis' above and 'Pregnancy' above.)
Adults — We recommend PrEP for the following groups of adult patients who are at high risk of acquiring HIV based upon clinical trial data demonstrating the efficacy of PrEP in reducing the risk of HIV acquisition, and the low risk of severe adverse events related to TDF-FTC and TAF-FTC (see "Administration of pre-exposure prophylaxis against HIV infection", section on 'Efficacy of oral pre-exposure prophylaxis'):
●Men and women without HIV who have a sexual partner with HIV with a detectable viral load. Although PrEP can be considered for all individuals without HIV who have a serodiscordant partner, there is a very low likelihood of transmission if the partner with HIV is adherent to their antiretroviral therapy (ART) regimen and is confirmed to have a stably suppressed plasma HIV RNA (eg, typically by six months after initiating ART). (See "HIV infection: Risk factors and prevention strategies", section on 'Treatment as prevention'.)
If the patient's partner recently initiated ART, PrEP may not need to be continued indefinitely. The duration of PrEP in this setting is discussed elsewhere. (See "Administration of pre-exposure prophylaxis against HIV infection".)
●Men who have sex with men (MSM) and transgender women who have sex with men if, within the last six months, they have engaged in high-risk sexual behaviors or had a documented bacterial sexually transmitted infection [8]. High-risk behaviors include condomless anal sex (insertive or receptive) with multiple or anonymous sex partners (or a main partner with HIV risk factors).
●Heterosexually active men who have condomless sex with female partners from regions with generalized HIV epidemics. According to the World Health Organization (WHO), this refers to geographic regions or populations where the prevalence of HIV is ≥3 percent [50]. However, other guideline panels have suggested a lower prevalence threshold of ≥2 percent [51].
We also suggest PrEP for the following groups:
●Heterosexual men who have, in the last six months, been diagnosed with a bacterial sexually transmitted infection (STI) or have engaged in condomless sex with female partners from areas of low general HIV prevalence but who are at high risk of HIV infection (eg, sex workers, injection drug users).
●Heterosexual cisgender women and transgender men who have, in the last six months, been diagnosed with a bacterial STI or have engaged in condomless sex with male partners who are at high risk of HIV infection (eg, injection drug users, bisexual male partners, partners from areas where there is a high HIV prevalence).
●Injection drug users who, within the last six months, report sharing needles/equipment, even if they have initiated substance use treatment.
Clinical trial data support the use of PrEP in these groups; however, the results have been conflicting, or the data are more limited. (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Efficacy of oral pre-exposure prophylaxis'.)
On occasion, a patient may not endorse high-risk behaviors but still desire PrEP. In these circumstances, clinicians should try to better understand the patient's reasons for wanting to use PrEP and convey the risks and benefits of therapy. Patients who engage in high-risk behaviors may not be comfortable disclosing this information. Thus, we typically provide PrEP if we feel the potential risks and benefits of treatment are fully understood, and there are no underlying behavioral health issues that would impact their decision.
Adolescents — In the United States, TDF-FTC and cabotegravir have been approved by the US Food and Drug Administration (FDA) for use as PrEP in adolescent patients who weigh at least 35 kg [52]. TAF-FTC is also approved for use as PrEP in adolescent patients who weigh at least 35 kg and do not engage in receptive vaginal sex. Young MSM are at particularly high risk of acquiring HIV [53,54]. Among MSM aged 13 to 24 years, the rate of new infections increased by 43 percent from 2003 to 2014 [54].
The Adolescent Trials Network (ATN) studied daily TDF-FTC PrEP in 78 patients 15 to 17 year of age [55]. TDF-FTC was well tolerated among those who took their medication; however, adherence was suboptimal for many of the youth (protective levels of tenofovir were found in approximately 50 percent at 12 weeks when they were being seen every four weeks, but only in 22 percent at 48 weeks when visits were quarterly). The findings from this study suggest that potential barriers to adherence should be identified and addressed. In addition, for younger MSM, more frequent provider-patient contact may be important. Additional studies are underway to assess whether adherence support can be effectively delivered via apps or other social media.
In addition to addressing adherence, clinicians must weigh the potential risk of bone effects with the relative risk of acquiring HIV. The bone loss seen with TDF may pose additional risks in adolescent compared with adult men, as described above (see 'Osteoporosis' above). Studies are underway to determine if there are ways to reduce these effects (eg, calcium and vitamin D supplementation). Regimen selection in the setting of osteoporosis risk is discussed elsewhere. (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Oral regimens'.)
Patients transitioning from postexposure prophylaxis — For HIV-uninfected patients not taking PrEP, a three-drug antiretroviral regimen can be administered after a potential HIV exposure. This regimen is administered for 28 days and is referred to as nonoccupational postexposure prophylaxis (nPEP). The use of nPEP is discussed in detail elsewhere. (See "Management of nonoccupational exposures to HIV and hepatitis B and C in adults", section on 'Exposure to HIV'.)
Patients who receive repeated courses of nPEP should be offered PrEP. For those who decide to transition from nPEP to PrEP, a repeat HIV test should be performed at the end of the 28-day course.
●The patient can transition from their nPEP regimen to a regimen for PrEP if HIV testing is negative, there is no concern for acute HIV, and there are no other contraindications to the PrEP regimen. (See 'Assessing risk of treatment' above and 'Administration of PrEP' below.)
●By contrast, nPEP should be continued pending further evaluation if there is any suspicion for HIV infection (eg, indeterminate HIV test, symptoms of acute infection). (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)
ADMINISTRATION OF PrEP — For patients who initiate pre-exposure prophylaxis (PrEP), tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) or tenofovir alafenamide-emtricitabine should be taken daily. Alternative dosing approaches with TDF-FTC may be an option for certain individuals who can reliably predict when they will have condomless sex, although less than daily PrEP dosing has not been approved by the US Food and Drug Administration. Injectable therapy with cabotegravir is also an option for PrEP. (See "Administration of pre-exposure prophylaxis against HIV infection".)
Patients receiving PrEP should receive counseling on other risk reduction methods, and should be monitored every three months to ensure there are no drug-related toxicities and that there is no evidence of HIV acquisition. Patients should continue PrEP as long as the risk of infection persists. A detailed discussion of how to administer and monitor patients taking PrEP is presented elsewhere.(See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Patient monitoring'.)
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: Diagnosis of hepatitis B".)
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 topics (see "Patient education: Taking medicines to prevent HIV before exposure (The Basics)")
SUMMARY AND RECOMMENDATIONS
●For patients without HIV who are at high risk for acquiring HIV and are committed to medication adherence, pre-exposure prophylaxis (PrEP) can reduce the risk of HIV transmission by greater than 90 percent. (See 'General Approach' above.)
●Selecting patients for PrEP requires an assessment of the risk of acquiring HIV, the risk associated with treatment, and the patient's willingness to adhere to treatment (table 1). Testing for HIV infection and renal function are required prior to treatment to evaluate for potential contraindications (eg, TDF and TAF should not be used in patients with severely reduced kidney function). Additional considerations for risk and benefit include hepatitis B virus infection, osteoporosis, and pregnancy.
●We recommend PrEP for the following adults without HIV who are at high risk for HIV transmission (Grade 1A) (see 'Candidates for PrEP' above):
•Men and women who have a sexual partner with HIV and a detectable viral load.
•Men who have sex with men (MSM) and transgender women who have sex with men if, within the last six months, they have engaged in high-risk sexual behavior (eg, condomless anal sex with multiple or anonymous partners) or have had a documented bacterial sexually transmitted infection (STI).
•Heterosexual men who have condomless sex with female partners from areas of high general HIV prevalence (eg, sub-Saharan Africa).
●We also suggest PrEP for other high-risk adult populations who are HIV uninfected (Grade 2B). These include (see 'Candidates for PrEP' above):
•Heterosexual men who have, in the last six months, been diagnosed with a bacterial STI or have engaged in condomless sex with female partners from areas of low general HIV prevalence but with high-risk behavior (eg, sex work, injection drug use).
•Heterosexual women who have, in the last six months, been diagnosed with a bacterial STI or have engaged in condomless sex with male partners who are at high risk of HIV infection (eg, injection drug users, bisexual male partners, partners from areas where there is a high HIV prevalence).
•Injection drug users who, within the last six months, report sharing needles/equipment.
●PrEP is generally not needed for patients who engage in low-risk behaviors (eg, consistent condom use, exclusive oral sex). (See 'Candidates for PrEP' above.)
●Young MSM are at particularly high risk of acquiring HIV. When deciding to prescribe PrEP to adolescents, providers should identify and address barriers to adherence and weigh the potential increased risk of bone effects with the relative risk of acquiring HIV. (See 'Adolescents' above.)
●Selecting between options for PrEP is discussed elsewhere. (See "Administration of pre-exposure prophylaxis against HIV infection", section on 'Oral regimens'.)
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.
