PrEP for HIV Prevention: Who Should Take It, How It Works, and How to Get It

Pre-exposure prophylaxis, universally known as PrEP, is a preventive medication strategy for people who are HIV-negative but at substantial risk of HIV acquisition. When taken consistently, PrEP reduces the risk of getting HIV from sex by approximately 99 percent and from injection drug use by at least 74 percent. These are not modest gains at the margins — they represent near-complete protection, making PrEP one of the most powerful infectious disease prevention tools developed since the introduction of hepatitis B vaccination. Despite this efficacy, only a fraction of the estimated 1.2 million Americans who could benefit from PrEP are currently taking it, with significant disparities by race, gender, geography, and socioeconomic status. Addressing knowledge gaps, access barriers, and stigma around PrEP is a direct public health priority.

How PrEP Works

All currently approved PrEP medications work by maintaining active antiretroviral drug concentrations in the bloodstream and target tissues — particularly the rectal mucosa, genital tract, and blood — at levels that suppress HIV replication before the virus can establish a systemic infection. HIV must replicate within cells to establish infection; if effective concentrations of reverse transcriptase inhibitors are present in the exposed tissue at the time of exposure, viral replication is interrupted before the infection can take hold. The drugs do not neutralize HIV in the body — they prevent it from replicating in tissues where it would otherwise establish latent reservoirs.

This is also why adherence is so critical: PrEP levels in rectal tissue build to protective concentrations after approximately seven days of daily dosing, while vaginal tissue requires longer (approximately 21 days for consistent protection with tenofovir DF/emtricitabine). A missed dose does not immediately remove protection, but irregular adherence creates windows of vulnerability — the drug's tissue concentrations are insufficient to halt replication if exposure occurs during those windows. For rectal exposure (receptive anal intercourse), the protective threshold is reached more quickly, which is why research has examined on-demand dosing (described below).

The Three Approved PrEP Options

Truvada (Tenofovir Disoproxil Fumarate / Emtricitabine)

Truvada (TDF/FTC) was the first FDA-approved PrEP medication (2012) and has the largest body of real-world evidence, including the landmark iPrEx trial demonstrating 44 percent overall reduction in HIV incidence (and 92 percent reduction in participants with detectable drug levels, confirming that adherence drives efficacy). TDF/FTC is effective for all populations, taken as one pill daily. A potential concern is its modest effect on bone mineral density and renal tubular function with long-term use — markers typically return to baseline after discontinuation. It is now available as generic tenofovir DF/emtricitabine, which has dramatically reduced cost for those paying out of pocket.

Descovy (Tenofovir Alafenamide / Emtricitabine)

Descovy (TAF/FTC) was approved for PrEP in 2019 for cisgender men and transgender women who have sex with men. It is not approved for cisgender women or for people who practice receptive vaginal sex because the DISCOVER trial, which established Descovy's efficacy, did not include these populations, leaving a data gap. TAF/FTC achieves equivalent antiviral efficacy to TDF/FTC but with lower tenofovir plasma levels (higher intracellular levels through a different prodrug strategy), resulting in a better renal and bone safety profile. This makes Descovy preferable for people with pre-existing kidney disease or low bone density. It is not yet available as a generic in the US, making it more expensive for uninsured patients.

Apretude (Cabotegravir Injectable)

Apretude (long-acting injectable cabotegravir) was FDA-approved in December 2021 as the first injectable PrEP option. It is administered as intramuscular injections: an initial injection, a second injection four weeks later, and then every two months thereafter. The HPTN 083 and HPTN 084 trials demonstrated that Apretude was superior to daily oral TDF/FTC in both men who have sex with men/transgender women and in cisgender women in sub-Saharan Africa — substantially higher real-world protection attributed to elimination of adherence as a variable. For patients who struggle with daily pill adherence, Apretude is transformative. Considerations include the requirement for clinic visits every two months, injection site reactions (pain, swelling), and a longer drug tail-off period after stopping (months, not days), which means any emergent HIV infection during that period must be recognized and treated to prevent resistance.

Who Qualifies for PrEP: CDC Guidelines

The CDC's clinical practice guideline identifies populations for whom PrEP should be offered:

• Sexually active adults who are at substantial risk of HIV acquisition, defined as:
• HIV-negative adults with an HIV-positive sexual partner (any sex)
• Men who have sex with men (MSM) who have had anal sex without consistent condom use in the past six months, or who have had a bacterial STI (gonorrhea, syphilis, chlamydia) in the past six months
• Heterosexually active adults who inconsistently use condoms with a partner of unknown HIV status who is at substantial HIV risk (e.g., a partner who injects drugs or bisexual partner)
• People who inject drugs (PWID) who share injection equipment or have a recent bacterial infection from injecting
• People who have exchanged sex for money, housing, or commodities
• People in geographic areas with high HIV prevalence (many US cities, rural South) and who have a recent STI

The 2021 CDC guidelines additionally recommend that clinicians offer PrEP to anyone who requests it after discussing risk and indication. Gatekeeping PrEP from patients who want it perpetuates inequity and missed prevention opportunities.

Required Testing Before and During PrEP

Before Starting

HIV testing (negative result required before initiating PrEP — starting PrEP in an HIV-positive person risks selecting for resistance to the antiretrovirals). Renal function (serum creatinine, eGFR — TDF/FTC requires eGFR ≥ 60 mL/min; TAF/FTC requires eGFR ≥ 30 mL/min). STI testing (gonorrhea, chlamydia, syphilis, hepatitis B surface antigen and antibody, hepatitis C). Pregnancy test for individuals who can become pregnant (TDF/FTC is safe in pregnancy; TAF/FTC data are more limited; cabotegravir is not approved in pregnancy). Bone density testing is not routinely required but may be considered in patients with risk factors.

Monitoring During PrEP

Follow-up visits every three months (or every two months for injectable PrEP) for: HIV testing (essential — HIV must not be missed while on PrEP), STI screening, renal function (creatinine), pregnancy testing if relevant, and medication adherence counseling. The three-month interval is not arbitrary — it is the frequency at which real-world data show adequate safety monitoring and HIV status confirmation. STI testing at this frequency has the added benefit of detecting and treating bacterial STIs more promptly, which independently reduces HIV transmission risk.

Side Effects and Kidney Monitoring

TDF/FTC (Truvada and generic): nausea, headache, and fatigue are common in the first few weeks and typically resolve. Modest, generally reversible decreases in bone mineral density occur with long-term use. Renal tubular dysfunction is rare at standard PrEP doses but requires monitoring. Patients with pre-existing kidney disease should use Descovy or discuss the risk profile with their prescriber. TAF/FTC (Descovy): similar mild initial side effects. Weight gain has been noted with TAF-containing regimens, of uncertain clinical significance. Injectable cabotegravir: injection site reactions (pain, swelling, nodule at injection site) are the most common side effect, affecting up to 80 percent of patients at some point but severe in fewer than 3 percent.

PrEP and STI Screening

An important secondary benefit of PrEP programs is the structured STI screening that accompanies them. PrEP users receive STI testing every three months — a frequency that dramatically exceeds testing rates in the general population and in many high-risk individuals not in PrEP care. Data from PrEP cohorts show high rates of gonorrhea, chlamydia, and syphilis detected and treated during routine PrEP visits — infections that would otherwise go undetected and untreated. PrEP programs function, in effect, as high-frequency STI surveillance and treatment programs, providing a population health benefit beyond HIV prevention alone.

PEP vs PrEP

Post-exposure prophylaxis (PEP) is an entirely different intervention — a 28-day course of three antiretroviral medications started within 72 hours of a potential HIV exposure. PEP is an emergency intervention for discrete exposures: a condom break with an HIV-positive partner, a sexual assault, or a needlestick injury. Its efficacy decreases with each hour of delay past exposure and is negligible if started beyond 72 hours. PEP is not a substitute for PrEP in people with ongoing exposure risk — the appropriate next step after PEP is transitioning to PrEP if the risk context is recurring. PEP reduces transmission risk by approximately 80 percent; PrEP at full adherence reduces it by approximately 99 percent. The two tools serve complementary roles.

On-Demand PrEP (2-1-1 Dosing)

For cisgender men who have sex with men, an event-driven PrEP regimen demonstrated in the IPERGAY trial offers an alternative to daily dosing: two pills of TDF/FTC taken two to 24 hours before anticipated sex, one pill 24 hours after the first dose, and one pill 48 hours after the first dose. This approach showed 86 percent efficacy and is now included in French, European, and WHO guidelines, though not yet in US FDA labeling. On-demand PrEP is not appropriate for people with hepatitis B co-infection, people practicing vaginal sex (insufficient evidence), or people whose sexual activity is too frequent or unpredictable to allow reliable pre-dosing. For those who qualify, it reduces total pill burden and cost substantially.

Cost, Insurance, and ADAP Programs

PrEP medications are expensive at list price: Truvada is available as generic for approximately $30 to $80 per month; Descovy remains approximately $1,400 to $2,000 per month; Apretude is approximately $3,700 per injection. The Affordable Care Act mandates that commercial insurance plans cover PrEP without cost sharing (copay or deductible) as a preventive service following the USPSTF Grade A recommendation — though legal challenges to this mandate were ongoing as of 2025 and coverage varies by plan. For uninsured and underinsured patients, options include: generic TDF/FTC at low-cost pharmacies; Gilead's Advancing Access patient assistance program for Descovy; AIDS Drug Assistance Programs (ADAP) in every state, which provide PrEP at no cost to eligible low-income individuals; Ready, Set, PrEP, a federal program providing free PrEP medications to uninsured people meeting income requirements. No one who needs PrEP should forgo it solely because of cost — these programs exist specifically to address that barrier.

Addressing Stigma Around PrEP

PrEP is sometimes associated with negative social narratives — that it "enables promiscuity," is "only for gay men," or signals something about a person's sexual behavior that they should be ashamed of. These narratives are harmful, factually incorrect, and function as barriers to life-saving prevention. PrEP is a medical tool for reducing a communicable disease risk — no different in principle from a vaccine, seatbelt, or sun protection. It is available to and beneficial for anyone at substantial HIV risk, regardless of sexual orientation, gender identity, relationship structure, or past behavior. Providers who impose moral gatekeeping on PrEP access — requiring patients to justify their sexual behavior or implying judgment — are practicing medicine in a way that directly costs lives. Affirming, non-judgmental access is both an ethical and a public health requirement.

When to See a Doctor

If you think you might benefit from PrEP based on any of the risk categories described above — or simply want to discuss your HIV risk and options — a medical consultation is the right next step. The process of starting PrEP requires an HIV test, basic labs, and a prescription; it is straightforward and can be initiated at a primary care visit, sexual health clinic, or telehealth consultation. JourneyDoctors connects you with trained specialists from $19. Start a consultation today — no waiting room, no referral needed.

Disclaimer: This article is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional for diagnosis and treatment.

Frequently Asked Questions

Does PrEP protect against other STIs besides HIV?

No. PrEP does not provide any protection against gonorrhea, chlamydia, syphilis, herpes, HPV, or hepatitis C. Condoms remain the most effective mechanical barrier against STI transmission. One practical benefit of PrEP programs is that the required three-monthly STI testing catches and treats bacterial STIs promptly — but the medication itself offers no protection. This is an important point for patients who may reduce condom use after starting PrEP without understanding this distinction.

How quickly does PrEP start working?

For receptive anal sex (the highest-risk sexual act for HIV), TDF/FTC reaches protective levels in rectal tissue after approximately seven days of consistent daily dosing. For receptive vaginal sex, approximately 21 days of consistent dosing is needed to reach protective levels in cervicovaginal tissue. Injectable cabotegravir provides protection from the first injection within approximately one week. A barrier method (condom) should be used during the initial period before PrEP reaches protective levels.

Can I stop and restart PrEP?

Yes. PrEP is not lifelong treatment for most people — it is appropriate for periods of elevated risk, which may be intermittent over a lifetime. Stopping PrEP when risk decreases (entering a mutually monogamous relationship, stopping injection drug use, undergoing behavioral changes) is entirely appropriate. Before stopping TDF/FTC, completing a final two-day tail-off (taking the last dose two days after the last potential exposure) is recommended to ensure adequate drug levels through the exposure window. For people with hepatitis B, stopping TDF-containing PrEP requires careful management because TDF is also active against hepatitis B, and stopping abruptly can trigger hepatitis flares.

Is PrEP safe long-term?

Long-term data from clinical trials (10-plus years) and real-world PrEP programs consistently show that PrEP is safe for long-term use. TDF/FTC causes modest, reversible decreases in bone mineral density and minor renal changes in some patients; TAF/FTC has a better renal and bone safety profile. Annual monitoring catches any emerging issues. The long-term risks of PrEP are substantially lower than the risks of HIV infection — a disease that, if untreated, is fatal, and even when treated, requires lifelong antiretroviral therapy with its own side effect profile.

What happens if I test HIV-positive while on PrEP?

This situation — which is uncommon with consistent PrEP adherence — requires immediate specialist evaluation. The HIV must be fully genotyped to assess for resistance to the PrEP medications, and antiretroviral treatment must be initiated promptly with agents that are active against the specific virus strain. The reason HIV testing is required every three months during PrEP is precisely to detect any incident infection before it progresses or before resistance develops from ongoing PrEP exposure in an HIV-positive person.