Draft Recommendation Statement
Prevention of HIV Infection: Pre-Exposure Prophylaxis
December 13, 2022
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
- Update in Progress for Prevention of HIV Infection: Pre-Exposure Prophylaxis
|Adolescents and adults at increased risk of HIV||The USPSTF recommends that clinicians prescribe pre-exposure prophylaxis with effective antiretroviral therapy to persons who are at increased risk of HIV acquisition to decrease the risk of acquiring HIV infection. See the "Practice Considerations" section for more information about identification of persons at increased risk and about effective antiretroviral therapy.||A|
Pathway to Benefit
To achieve the benefit of HIV pre-exposure prophylaxis, it is important that persons receive counseling about antiretroviral medication adherence and safer sex, including condom use, regular testing for HIV, and other necessary testing. See the "Practice Considerations" section for more information about initial and followup assessment, testing, and monitoring.
- Draft Evidence Review (December 13, 2022)
- Final Research Plan (January 13, 2022)
- Draft Research Plan (November 04, 2021)
- Pre-exposure Prophylaxis for the Prevention of HIV Infection (Consumer Guide): Draft Recommendation | Link to File
|Table of Contents||PDF Version and JAMA Link||Archived Versions|
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
An estimated 1.2 million persons in the United States currently have HIV,1 and more than 760,000 persons have died of AIDS since the first cases were reported in 1981.2 In 2020, there were an estimated 30,635 new diagnoses of HIV infection in the United States (though this may be an underestimate due to the COVID-19 pandemic), with 80% (24,488) of new diagnoses occurring among adolescent and adult men and 18% (5,450) among adolescent and adult women.3 Men who have sex with men are most affected by HIV, accounting for 68% of new HIV diagnoses in 2020.3
There are also racial and ethnic disparities in the incidence of HIV, with 42% of new diagnoses occurring among Black persons, 27% among Hispanic/Latino persons, and 26% among White persons in 2020.3 Though treatable, HIV infection is not curable and has significant health consequences. Therefore, effective strategies to prevent HIV infection are an important public health and clinical priority.
The U.S. Preventive Services Task Force (USPSTF) concludes with high certainty that there is a substantial net benefit from the use of effective antiretroviral therapy to reduce the risk of acquisition of HIV infection in persons who are at increased risk of HIV infection.
Go to the Table for more information on the USPSTF recommendation rationale and assessment. For more details on the methods the USPSTF uses to determine the net benefit, see the USPSTF Procedure Manual.4
Patient Population Under Consideration
This recommendation applies to adolescents and adults who are not infected with HIV and are at increased risk of HIV infection.
Assessment of Risk for HIV Acquisition
HIV infection is primarily acquired via sexual activity or injection drug use. It is important that clinicians routinely take a sexual and injection drug use history for all their patients in an open and nonjudgmental manner. All adults and adolescents who are sexually active or who inject drugs should be informed that HIV infection can be prevented, to facilitate subsequent risk assessment and discussions about pre-exposure prophylaxis (PrEP) and other ways to prevent HIV. Importantly, risk of HIV acquisition exists on a continuum, and no well-validated accurate risk assessment tool exists. However, certain risk factors or behaviors are known to place persons at increased risk of HIV infection.
Risk of HIV acquisition depends on the likelihood that a specific act or activity will transmit HIV and the likelihood that a sex partner or drug injection partner has HIV. Likelihood of HIV transmission is highest with needle-sharing injection drug use and condomless receptive anal intercourse. Condomless receptive anal intercourse has an approximately 10- to 15-fold higher risk of transmission than condomless insertive anal sex and condomless receptive and insertive penile-vaginal sex.5 A 2018 study estimated the prevalence of HIV (i.e., an estimate of the likelihood that a partner whose HIV status is unknown has HIV at a population level) as 12.4% among men who have sex with men and 1.9% among persons who inject drugs.6 The overall prevalence of HIV in the United States is estimated at 0.3%.3 Of note, both the frequency of specific sexual activities and a person’s number of sexual partners will also affect their risk of HIV.
The USPSTF recommends that the following persons be considered for PrEP:
- Sexually active adults and adolescents weighing at least 35 kg (77 lb) who have engaged in anal or vaginal sex in the past 6 months and have any of the following:
- A sexual partner who has HIV (especially if the partner has an unknown or detectable viral load).
- A bacterial sexually transmitted infection (STI) (syphilis, gonorrhea, or chlamydia for men who have sex with men and transgender women; gonorrhea and syphilis for heterosexual women and men) in the past 6 months.
- A history of inconsistent or no condom use with sex partner(s) whose HIV status is not known; assessing risk in conversation with the patient and considering factors such as number of partners, the specific sexual activities a person engages in, and whether their sex partner or partners are in a group with a higher prevalence of HIV (e.g., men who have sex with men or with men and women, transgender women, persons who inject drugs, and persons who engage in transactional sex).
- Persons who inject drugs and have a drug injecting partner who has HIV or who shares injection equipment.
Persons who engage in transactional sex, such as sex for money, drugs, or housing, including commercial sex workers or persons trafficked for sex work, constitute a group at high/increased risk of HIV acquisition and should be considered for PrEP based on the criteria outlined above. Transgender women and men who are sexually active should be considered for PrEP based on the criteria outlined above. Transgender women are at especially high risk of HIV acquisition. A Centers for Disease and Prevention (CDC) survey in seven cities found an HIV prevalence of 42% among transgender women. Prevalence was highest among Native American/Alaska Native transgender women (65%) and Black transgender women (62%).7
In addition, studies have found that transmission of HIV to a seronegative partner from a partner with HIV has not been observed when the partner with HIV was being treated with antiretroviral therapy and had a suppressed viral load.8-10 It is not known whether PrEP use further decreases the risk of HIV transmission when a partner with HIV has a documented undetectable viral load. Factors such as the consistency or inconsistency of a partner’s viral load being suppressed, a partner’s adherence to antiretroviral therapy, and the degree of certainty that a partner’s viral load is suppressed (e.g., self-report vs. availability of laboratory test results) may help inform decisions about the use of PrEP in this situation.
All persons being considered for PrEP must have a recently documented negative HIV antigen-antibody test result, and if they have taken oral PrEP or post-exposure prophylaxis in the past 3 months, or injectable cabotegravir in the past 12 months, the CDC recommends testing with both an HIV antigen-antibody assay and an HIV-1 RNA assay.11
Medication for Prevention of HIV Infection
Currently, several medications are approved by the U.S. Food and Drug Administration (FDA) for use as PrEP. Oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) and injectable cabotegravir are approved by the FDA for use in at-risk adults and adolescents weighing at least 35 kg (77 lb) to reduce the risk of sexually acquired HIV infection.12,13 Oral tenofovir alafenamide-emtricitabine (TAF-FTC) is approved by the FDA for use in at-risk adults and adolescents weighing at least 35 kg (77 lb) to reduce the risk of sexually acquired HIV infection, excluding individuals at risk from receptive vaginal sex.14 No PrEP medications have FDA approval for reducing the risk of acquiring HIV infection via injection drug use, but CDC guidelines note that persons who inject drugs are likely to benefit from PrEP with any FDA-approved PrEP medication.11 No trials of PrEP enrolled persons who were pregnant. FDA labelling permits the use of TDF-FTC in pregnant persons. It also permits the use of TDF-FTC in persons who are breastfeeding and recommends that the potential benefits should be considered along with any potential adverse effects on the breastfed child.
The first step in implementing PrEP is identifying persons at increased risk of HIV acquisition who may benefit from PrEP. However, identifying persons at risk of HIV can be challenging because of stigma and discrimination against gay, bisexual, transgender, and nonbinary persons and persons who inject drugs, or the lack of a trusting relationship between the patient and clinician. It is important that clinicians routinely take a sexual and injection drug use history for all their patients in an open and nonjudgmental manner and inform all persons who are sexually active or who inject drugs that HIV infection can be prevented. This can facilitate the subsequent discussion between clinician and patient about factors or behaviors that may make a person an appropriate candidate for PrEP.
As noted, FDA labelling permits the use of TDF-FTC in pregnant persons at risk of acquiring HIV.12 PrEP with TDF-FTC, TAF-FTC, and cabotegravir are also approved for use in adolescents at risk of acquiring HIV who weigh at least 35 kg (77 lb).12-14 Clinicians need to be aware of any local laws and regulations that may apply when providing PrEP to an adolescent minor.
The CDC provides a complete discussion of implementation considerations for PrEP, including baseline and followup testing and monitoring and discontinuing PrEP.11 A few particularly important points regarding the provision of PrEP are outlined below.
Before prescribing PrEP, clinicians should exclude persons with acute or chronic HIV infection through taking a medical history and HIV testing. In persons who have taken oral PrEP or post-exposure prophylaxis in the past 3 months, or a cabotegravir injection in the past 12 months, the CDC recommends HIV testing with both an HIV antigen-antibody assay and an HIV-1 RNA assay. If they have not, an HIV antigen-antibody assay is recommended as the initial test.11 The antiretroviral regimens used in PrEP, when used alone, are not effective treatments for HIV infection, and their use in persons with HIV infection can lead to the emergence of, or selection for, drug-resistant HIV. It is also generally recommended that kidney function testing, serologic testing for hepatitis B and C virus, testing for other STIs, and pregnancy testing (when appropriate) be conducted at the time of or just before initiating PrEP. Ongoing followup and monitoring, including HIV testing every 2 to 3 months, depending upon PrEP formulation used, is also recommended. The time from initiation of PrEP to achieving protection against HIV infection is unknown. Pharmacokinetic studies of TDF-FTC suggest that maximum intracellular concentrations of the active form of tenofovir are reached in peripheral blood mononuclear cells and rectal tissue after approximately 7 days of daily oral dosing and in cervicovaginal tissues at approximately 20 days.11 Patients can continue PrEP as long as risk of HIV acquisition continues. Patients may discontinue PrEP for several reasons, including personal preference, decreased risk of HIV acquisition, or adverse medication effects.
PrEP does not reduce the risk of other STIs. Consistent use of condoms decreases risk of HIV acquisition by approximately 80%5 and reduces the risk of other STIs. Promoting consistent condom use is an important component of successful PrEP implementation. The CDC also recommends regular screening for STIs in persons taking PrEP, and STI and HIV testing in anyone with signs or symptoms.11
Clinical trials demonstrate a strong connection between adherence to PrEP and its effectiveness in preventing HIV acquisition.15 Low adherence is associated with a marked decrease in effectiveness. Therefore, adherence support is a key component of providing PrEP. Components of adherence support include establishing trust and open communication with patients, patient education, reminder systems for taking medication, and attention to medication adverse effects and having a plan to address them. Additional information on adherence support is available in the CDC guidelines.11,16 Adherence support is especially important in populations known to have lower adherence to PrEP, such as young persons and racial and ethnic minorities.17,18
It is important for clinicians to recognize that barriers to the implementation and uptake of PrEP exist. These barriers can include structural barriers, such as lack of health insurance, and other factors, such as an individual’s belief that they are an appropriate candidate for PrEP or willingness to take PrEP. There are also racial and ethnic disparities in the use of PrEP. Although Black persons are estimated to account for approximately 40% of persons in the United States with indications for PrEP, CDC data indicate that the number of White persons prescribed PrEP was approximately 5 times higher than the number of Black persons in 2019.19 The CDC has estimated that the proportion of persons with indications for PrEP who received it was 60.5% among White persons vs. 7.9% in Black persons and 13.8% in Hispanic/Latino persons.19 Another study reported that Black women, who are also disproportionately affected by HIV, were more than 4 times less likely to have initiated PrEP than White women.20 CDC data also showed disparities in PrEP use relative to indications for PrEP (PrEP coverage) by sex (lower in females than in males) and age (lower in persons ages 16 to 24 years than in those age 25 years or older).19 Limited data suggest that PrEP use is lower in transgender women than in men who have sex with men.21 These barriers and disparities need to be addressed to achieve the full benefit of PrEP.
Additional Tools and Resources
The CDC provides guidelines on PrEP for the prevention of HIV infection (https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf and https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-provider-supplement-2021.pdf). The CDC also provides additional resources on PrEP for both clinicians and consumers (https://www.cdc.gov/hiv/risk/prep/index.html). County and state-level HIV prevalence data for the United States are available (https://www.cdc.gov/nchhstp/atlas).
Other Related USPSTF Recommendations
The USPSTF has issued recommendations on behavioral counseling to reduce risk of STIs,22 screening for HIV infection,23 screening for syphilis in pregnant24 and nonpregnant persons,25 screening for genital herpes,26 and screening for chlamydia and gonorrhea.27
When final, this recommendation will replace the 2019 USPSTF recommendation on PrEP for the prevention of HIV infection. In 2019, the USPSTF recommended that clinicians offer PrEP with effective antiretroviral therapy to persons who are at high risk of HIV acquisition.28 This draft recommendation is consistent with the 2019 recommendation. For the current draft recommendation, the USPSTF reviewed additional evidence on new formulations of PrEP and again recommends that clinicians prescribe PrEP with effective antiretroviral therapy to persons who are at increased/high risk of HIV acquisition, after the clinician and patient have discussed PrEP and the patient agrees.
Scope of Review
To update its 2019 recommendation statement, the USPSTF commissioned a systematic review15 of the evidence on the benefits and harms of PrEP with TDF-FTC, TDF alone, the dapivirine vaginal ring, TAF-FTC, and injectable cabotegravir for the prevention of HIV infection, and the diagnostic accuracy of risk assessment tools to identify persons at high risk of HIV acquisition.
Effectiveness of Risk Assessment
The USPSTF found 12 studies that evaluated risk assessment tools developed in U.S. cohorts for predicting incident HIV infection. Eight studies were conducted in men who have sex with men, one in persons who inject drugs, one in cisgender women, and two in the general population.15 Among the studies in men who have sex with men and persons who inject drugs that reported it, discrimination of the risk assessment tool was moderate, with an area under the receiver operating characteristic curve of 0.60 to 0.73.15 The two studies conducted in the general population evaluated two different risk assessment tools (number of items, 23 and 44) that used automated computerized algorithms on electronic medical record data. These two studies reported moderate to high discrimination for incident HIV infection (area under the receiver operating characteristic curve, 0.77 [95% CI, 0.74 to 0.79] and 0.84 [95% CI, 0.80 to 0.89]).29,30 One study focused on cisgender women who had a positive HIV test. It found that a six-item risk assessment tool, based on electronic medical record data, had sensitivity of 95% for incident HIV infection (21 cases).31
All of these studies had some limitations. Most of the risk assessment tools were developed and validated using previously collected data (i.e., not prospectively validated). The study of cisgender women focused only on persons with a new positive HIV test; thus only sensitivity but not other measures of test accuracy could be calculated. Additionally, it was based on a small number of incident cases. The feasibility of implementation of risk assessment tools based on computerized algorithms of electronic medical record data is unknown. Last, some studies used older cohorts (prior to 2000), and several studies did not predefine the cut-off for a positive test.15
Benefits of Preventive Medication
The USPSTF found 17 trials that compared a variety of formulations of PrEP with placebo or PrEP with TDF-FTC. Twelve trials compared TDF-FTC or TDF alone with placebo, two trials compared the dapivirine vaginal ring with placebo, one trial compared TAF-FTC with TDF-FTC, and two trials compared injectable cabotegravir with TDF-FTC.15
In the 12 trials of TDF-FTC or TDF alone, duration of followup ranged from 4 months to 4 years. Six trials enrolled men and women at risk of HIV infection via heterosexual contact, four trials enrolled men who have sex with men or transgender women, one trial enrolled at-risk women and men who have sex with men, and one trial enrolled persons who inject drugs. No trial enrolled pregnant persons or persons younger than age 18 years. Seven trials were conducted in Africa, one in Thailand, two in Europe or Canada, and one in the United States; one trial was multinational. All trials of persons at risk of HIV infection via heterosexual contact were conducted in Africa. All trials included behavioral and adherence counseling, and most provided condoms to all trial participants.15
In a pooled analysis, TDF-FTC or TDF alone was associated with significantly decreased risk of HIV infection vs. placebo or no PrEP (11 trials, N=18,172; relative risk [RR], 0.46 [95% CI, 0.33 to 0.66]; absolute risk reduction [ARR], -2.0% [95% CI, -2.8% to -1.2%] after 4 months to 4 years).15
There was a strong association between degree of adherence (assessed in different studies by methods such as patient self-report, pill counts, adherence monitoring devices, plasma drug levels, and prescription fill data) and the effectiveness of oral PrEP (p<0.00001 for interaction). In six trials where adherence was 70% or greater, the relative risk of HIV acquisition was 0.27 (95% CI, 0.19 to 0.39), in three trials where adherence was greater than 40% to less than 70%, the relative risk was 0.51 (95% CI, 0.38 to 0.70), and in two trials where adherence was 40% or less, oral PrEP was not associated with a decreased risk of HIV (RR, 0.93 [95% CI, 0.72 to 1.20]).15
Oral PrEP with TDF-FTC or TDF alone was consistently associated with decreased risk of HIV infection vs. placebo when trials were stratified according to HIV risk category (men who have sex with men, men and women at risk via heterosexual contact, or persons who inject drugs) or setting (highly developed or less highly developed countries).15 The effectiveness of TDF alone (RR, 0.49 [95% CI, 0.28 to 0.84]) and TDF-FTC (RR, 0.44 [95% CI, 0.27 to 0.72]) were similar.15 All trials evaluated daily PrEP, with the exception of one trial of event-driven PrEP (consisting of two tablets of TDF-FTC 2 to 24 hours before intercourse, followed by one tablet 24 hours and 48 hours after the first dose) in men who have sex with men. This trial found event-driven PrEP was associated with a significantly decreased risk of HIV infection compared with placebo (RR, 0.14 [95% CI, 0.03 to 0.63]),32 though in that trial, men randomly assigned to PrEP took an average of about four doses of PrEP per week, so it is uncertain whether this finding would apply to less frequent use of event-driven dosing.
In a pooled analysis of two trials, the dapivirine vaginal ring was associated with decreased risk of HIV infection compared with a placebo ring in African women at risk of HIV infection (N=4,564; RR, 0.71 [95% CI, 0.57 to 0.89]).15 The absolute risk reduction was -2.23% (95% CI, -3.75% to -0.74%) at 1.4 to 1.6 years.15 Notably, the dapivirine vaginal ring is not approved by the FDA.
One trial, DISCOVER (n=5,335), compared PrEP with oral TAF-FTC vs. TDF-FTC. It was conducted in Europe and North America and enrolled HIV-negative cisgender adult men (98.6%) and transgender women (1.4%) who have sex with men and are at risk of HIV acquisition, based on having condomless anal intercourse with at least two partners in the previous 12 weeks or an STI (syphilis, rectal gonorrhea, or rectal chlamydia) in the previous 24 weeks. At 96 weeks, TAF-FTC was associated with a nonstatistically significant decreased risk of HIV infection vs. TDF-FTC (0.3% vs. 0.6%; RR, 0.47 [95% CI, 0.19 to 1.14]); results were within the prespecified noninferiority margin (i.e., TAF-FTC was noninferior to TDF-FTC).33,34
Two trials (HIV Prevention Trials Network [HPTN] trials 083 and 084) compared long-acting injectable cabotegravir (600 mg intramuscular every 8 weeks, following a 5-week oral lead-in phase of 30 mg daily) vs. daily oral TDF-FTC.35,36 In HPTN 083 (n=4,566), 87% of participants were men who have sex with men and 12% were transgender women who have sex with men. Among U.S. participants (37% of total participants), 50% were Black. At median followup of 1.4 years, injectable cabotegravir was associated with a significantly decreased risk of HIV acquisition vs. oral TDF-FTC (0.6% vs. 1.7%; RR, 0.33 [95% CI, 0.18 to 0.62]). In stratified analysis, results were similar in men who have sex with men (hazard ratio, 0.35 [95% CI, 0.18 to 0.68]) and transgender women (hazard ratio, 0.34 [95% CI, 0.08 to 1.56]), although the estimate for transgender women was imprecise.35 HPTN 084 (n=3,178) was conducted in seven countries in sub-Saharan Africa. Participants were female (sex assigned at birth), were ages 18 to 45 years (median, 25 years), reported engaging in vaginal intercourse in the prior 30 days, and were assessed as being at risk for HIV acquisition using a risk prediction instrument developed and validated in African women. At median followup of 1.2 years, injectable cabotegravir was associated with a significantly decreased risk of HIV acquisition vs. oral TDF-FTC (0.3% vs. 2.3%; RR, 0.11 [95% CI, 0.04 to 0.31]).36
Harms of Preventive Medication
The trials that investigated the effectiveness of PrEP also reported on harms. Oral PrEP with TDF-FTC or TDF was associated with increased risk of renal adverse events (primarily grade 1 or higher creatinine elevation) (12 trials, N=18,170; RR, 1.43 [95% CI, 1.18 to 1.75]; absolute risk difference [ARD], 0.56% [95% CI, 0.09% to 1.04%]). Renal abnormalities generally resolved following PrEP cessation. Oral PrEP with TDF-FTC or TDF was associated with increased risk of gastrointestinal adverse events (12 trials, N=18,300; RR, 1.63 [95% CI, 1.26 to 2.11]; ARD, 1.95% [95% CI, 0.48% to 3.43%]), which were generally not serious and diminished over time. TDF-FTC and TDF were associated with a nonstatistically significant increased risk of fracture vs. placebo (7 trials, N=15,241; RR, 1.23 [95% CI, 0.97 to 1.56]); this outcome was heavily weighted by one trial conducted in persons who inject drugs.15
One trial (n=5,387) reported no differences between TAF-FTC and TDF-FTC in rates of any renal adverse events (1% vs. 1%) or risk of fracture (2% vs. 2%).34 Two trials (N=7,786) reported no differences between long-acting injectable cabotegravir and TDF-FTC in risk of decreased creatinine clearance or elevations in alanine or aspartate transaminase. Cabotegravir was associated with increased weight gain compared with TDF-FTC (mean differences, 0.86 and 0.4 kg) and increased risk of injection site reactions (most commonly pain) that were usually mild.35,36
One concern about PrEP is that its use may lead to persons at risk of HIV acquisition not using condoms or engaging in other behaviors that could increase their risk of STIs (i.e., behavioral risk compensation). In pooled analyses of randomized trials, there were no differences between PrEP with TDF-FTC or TDF and placebo in risk of syphilis (4 trials, N=10,775; RR, 1.08 [95% CI, 0.98 to 1.18]), gonorrhea (5 trials; RR, 1.07 [95% CI, 0.82 to 1.39]), chlamydia (5 trials; RR, 0.97 [95% CI, 0.80 to 1.18]), or combined bacterial STIs (2 trials; RR, 1.14 [95% CI, 0.97 to 1.34]),15 though all trials except for one were blinded, which could affect risk of STIs if participants who do not know whether they are taking PrEP or placebo behave differently than those who know they are taking PrEP. In the one open-label trial, there was also no statistically significant association between PrEP and the risk of STIs, though estimates were imprecise.37 Two trials of the dapivirine vaginal ring38,39 also reported no differences in risk of STIs vs. placebo.
An additional concern is the possibility that the use of antiretroviral drugs as PrEP could lead to the development or acquisition of drug-resistant HIV infection. Among all patients randomized to oral PrEP with TDF-FTC or TDF alone, 0.06% (2/3,149) of patients taking TDF (4 trials) and 0.3% (14/5,085) of patients taking TDF-FTC (7 trials) were identified as having incident HIV infection with a drug resistance mutation.15 Most resistance mutations occurred in persons who were already infected with HIV on trial enrollment but were not recognized as such, highlighting the importance of testing for HIV and excluding persons with HIV infection before initiating PrEP. In five observational studies of PrEP with TDF-FTC, two of 1,936 participants were diagnosed with an antiretroviral drug resistance mutation (0.1%).15 In the DISCOVER trial (n=5,335), among 19 patients who were infected with HIV and had resistance testing results, an emtricitabine resistance mutation was detected in four patients. All cases occurred in patients randomized to TDF-FTC who were suspected of having HIV infection at baseline.33
In two trials of the dapivirine (a non-nucleoside reverse transcriptase inhibitor [NNRTI]) vaginal ring, the proportion of patients randomized to dapivirine with an NNRTI resistance mutation was 0.8% (22/2,620). In both trials, the rate of NNRTI resistance mutations among patients with incident HIV infection was similar in patients randomized to the dapivirine vaginal ring vs. those randomized to placebo (11.8% [8/68] vs. 10.4% [10/96]; p=0.80)37 and (18.2% [14/77] vs. 16.1% [9/56]; p=0.75).39
In the HPTN 083 and HPTN 084 trials, which compared cabotegravir (an integrase strand transfer inhibitor [INSTI]) with TDF-FTC, among all patients randomized to cabotegravir, the proportion with an INSTI resistance mutation was 0.1% (4/3,874), though only 13 of 17 cases of incident HIV across both trials underwent resistance testing. Among individuals randomized to TDF-FTC across both trials, the proportion with antiretroviral resistance mutations was also 0.1% (5/3,870).35,36
Evidence on the effect of acquiring antiretroviral-resistant HIV infection on clinical outcomes is very limited. One study reported that among five patients previously exposed to PrEP and diagnosed with HIV infection with an M184V or M184I (emtricitabine) mutation, four had an undetectable viral load 3 months after starting antiretroviral therapy, and one patient was lost to followup.40 Another study included 52 persons diagnosed with HIV infection who reported recent PrEP exposure. All 39 individuals with a viral load greater than 200 copies/mL at baseline who received antiretroviral therapy achieved an undetectable viral load at 24 weeks. Results were not reported separately for patients with an antiretroviral resistance mutation.41
No trials of PrEP enrolled persons who were pregnant. However, among persons who became pregnant, a pooled analysis of three trials of TDF-FTC or TDF alone found that PrEP was not associated with increased risk of spontaneous abortion (3 trials, N=415; RR, 1.09 [95% CI, 0.79 to 1.50]).15 One trial found no differences between TDF-FTC or TDF alone and placebo in pregnancy rate, risk of preterm birth, congenital anomalies, or postpartum infant mortality.42 There were no differences between the dapivirine vaginal ring and placebo in incidence of pregnancy.38,39 In one trial of cabotegravir enrolling females, pregnancy incidence was low with both cabotegravir and TDF-FTC, and no congenital abnormalities were observed.36
Studies are needed that provide the following information.
- Research is needed to develop and validate tools that are accurate for identifying persons at increased risk of HIV acquisition who would benefit from PrEP. When developed and validated, risk assessment instruments should include those populations most at risk of HIV infection, including racial and ethnic groups such as Black and Hispanic/Latino populations.
- Research is needed on different drug regimens and dosing strategies for PrEP.
- Research is needed on factors associated with adherence to and persistence with PrEP and methods to increase uptake, adherence, and persistence, especially in populations with lower use of and adherence to PrEP, such as younger persons and racial and ethnic groups most affected by HIV.
- Studies or demonstration projects of PrEP in U.S. populations of heterosexual persons, persons who inject drugs, and transgender women and men are needed to better quantify effectiveness in those populations.
- Research is needed on the safety and effectiveness of PrEP during pregnancy and breastfeeding.
- Additional research is needed to determine whether the use of PrEP is associated with an increased risk of other STIs.
- Research is needed on the long-term safety and effectiveness of PrEP, including the longer-term effects of PrEP in adolescents, and the effect of INSTI resistance mutations on clinical outcomes.
The U.S. Public Health Service recommends PrEP for HIV prevention for sexually active adults and adolescents weighing at least 35 kg (77 lb) who report sexual behaviors that place them at substantial ongoing risk of HIV exposure and acquisition or who inject drugs and report injection practices that place them at substantial ongoing risk of HIV exposure and acquisition.11 The American College of Obstetricians and Gynecologists recommends discussing PrEP with all sexually active adolescents and adults and offering PrEP to those at substantial risk of HIV acquisition.43 The International Antiviral Society–USA Panel recommends PrEP for individuals at risk of HIV infection. It notes that identification of at-risk individuals for whom PrEP is recommended requires individualized approaches that consider past and future anticipated risk.44
1. Centers for Disease Control and Prevention. HIV Surveillance Report: Diagnoses of HIV Infection in the United States and Dependent Areas; 2019. Published May 2021. Accessed October 28, 2022. https://www.cdc.gov/hiv/library/reports/hiv-surveillance/vol-32/index.html
2. Centers for Disease Control and Prevention. HIV Infection, Stage 3 (AIDS): 2019. Accessed October 28, 2022. https://www.cdc.gov/hiv/pdf/library/slidesets/cdc-hiv-infection-stage-3-2019.pdf
3. Centers for Disease Control and Prevention. HIV Surveillance Report: Diagnoses of HIV Infection in the United States and Dependent Areas; 2020. Published May 2022. Accessed October 28, 2022. https://www.cdc.gov/hiv/library/reports/hiv-surveillance/vol-33/index.html
4. U.S. Preventive Services Task Force. Procedure Manual. Accessed November 3, 2022. https://uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes/procedure-manual
5. Patel P, Borkowf CB, Brooks JT, Lasry A, Lansky A, Mermin J. Estimating per-act HIV transmission risk: a systematic review. AIDS. 2014;28(10):1509-1519.
6. Singh S, Song R, Johnson AS, McCray E, Hall HI. HIV incidence, prevalence, and undiagnosed infections in U.S. men who have sex with men. Ann Intern Med. 2018;168(10):685-694.
7. Centers for Disease Control and Prevention. HIV Surveillance Report: HIV Infection, Risk, Prevention, and Testing Behaviors Among Transgender Women: National HIV Behavioral Surveillance, 7 U.S. Cities, 2019–2020. Published April 2021. Accessed October 28, 2022. https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-special-report-number-27.pdf
8. Bavinton BR, Pinto AN, Phanuphak N, et al; Opposites Attract Study Group. Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study. Lancet HIV. 2018;5(8):e438-e447.
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|Identification of risk status||
|Benefits of PrEP||
|Harms of PrEP||Adequate evidence that PrEP is associated with a small magnitude of harms, which include renal and gastrointestinal adverse effects, weight gain, and injection site reactions, depending on the specific PrEP formulation used.|
|USPSTF assessment||The USPSTF concludes with high certainty that there is a substantial net benefit from the use of effective antiretroviral therapy to reduce the risk of acquisition of HIV infection in persons who are at increased risk of HIV infection.|
*See the “Practice Considerations” section for more information about identification of persons at increased risk of HIV acquisition.
Abbreviations: HIV=human immunodeficiency virus; PrEP=pre-exposure prophylaxis; USPSTF=U.S. Preventive Services Task Force.