Pre‑exposure prophylaxis, or PrEP, changed how we prevent HIV. A once‑daily pill that pairs emtricitabine with tenofovir disoproxil fumarate creates a protective drug level in blood and tissues so the virus struggles to establish infection after exposure. For people with ongoing risk, PrEP can be more reliable than relying on condoms alone or trying to perfectly time sexual encounters around risk. The science is strong, but the day‑to‑day success still hinges on real lives, habits, and trade‑offs.
What the evidence actually shows about effectiveness
When taken as prescribed, emtricitabine/tenofovir (often called FTC/TDF) reduces the risk of sexually acquired HIV by roughly 99 percent. That figure comes from trials and real‑world cohorts in men who have sex with men and transgender women with high adherence. In vaginal exposure, protection remains high, but drug levels in the cervicovaginal tissues rise more slowly and can be more variable, so daily dosing matters even more. In people who inject drugs, trials showed risk reduction on the order of 70 to 84 percent with adherence, though estimates vary because injection exposures are harder to measure.
The gap between perfect and average use tells the story. When adherence drops, protection falls. A clinic I worked with tracked PrEP clients over 18 months. Seroconversions only occurred in those who had stopped PrEP or had prolonged gaps, most often after life events like moving, losing insurance, or depression flares. That pattern mirrors published data. PrEP is remarkably forgiving compared to many drugs, but it does not cover missed weeks.
Time to full protection depends on the tissue. For receptive anal sex, steady protection is reached after about 7 days of daily dosing. For receptive vaginal sex and for injection exposures, use a 21‑day window to be safe. People often ask about on‑demand or event‑based dosing. The 2‑1‑1 schedule has strong support for cisgender men who have sex with men who can plan sex at least 2 hours in advance. It is not recommended for receptive vaginal sex or for people who inject drugs due to different tissue pharmacology.
Who benefits most from PrEP
Risk is not a fixed label. It shifts with partners, relationships, local HIV prevalence, and substance use. The highest return usually occurs for people with new or multiple partners, those with a partner living with HIV who is not on treatment or not durably undetectable, and those with recent bacterial STIs. Injection drug use adds risk, especially when syringes are shared or when access to sterile supplies fluctuates.
I tend to ask practical questions instead of applying rigid checklists: Are there times when condoms are not used? Are there partners whose HIV status is unknown or who have partners beyond you? Are you in a region or network with higher community viral load? Have you had syphilis, gonorrhea, or chlamydia in the past year? Do you travel for work or pleasure and connect with new partners? If any answer is yes, PrEP deserves a careful discussion.
Getting started without losing momentum
Most clinics can complete baseline testing and start PrEP the same day. That approach captures motivation while it is high and avoids missed opportunities. The baseline steps are straightforward: an HIV antigen/antibody test, ideally with a rapid test and a lab send‑out if there are symptoms of acute HIV; screening for STIs at exposed sites; kidney function tests since tenofovir disoproxil can affect renal tubules; and, for people who can become pregnant, a pregnancy test and contraceptive counseling if desired. Hepatitis B status matters because both drugs also treat HBV, and stopping abruptly can trigger flares in people with chronic infection. Vaccinating against hepatitis B if non‑immune is a good idea.
Clinicians sometimes overcomplicate the first visit. I aim for clarity: here is how it works, here is how to take it, here are the labs, and here is the plan if you miss doses. We schedule the first follow‑up in one month to iron out early issues, then typically every 3 months. People feel reassured when they know the calendar.
Side effects you may feel, and what they mean
Most people tolerate FTC/TDF well. In the first week or two, a minority get a transient “start‑up syndrome” with queasiness, loose stools, or mild headaches. It tends to settle by week two. Taking the pill with food can help. I warn people to expect it so they are not caught off guard and tempted to stop too early.
Tenofovir disoproxil can cause small declines in kidney function in a subset of users, usually reversible and clinically modest. We check creatinine and estimated GFR at baseline and periodically. If someone starts near the lower limit of normal or has diabetes, hypertension, or is older, I keep a closer eye. Proximal tubulopathy is rare, but we think about it if there is unexplained phosphate loss or bone pain.
On bone mineral density, the average impact is small, most pronounced in adolescents and young adults, and often reverses after discontinuation. People with osteoporosis or on long‑term high‑dose prednisone may warrant a more tailored plan. In those cases, tenofovir alafenamide with emtricitabine is sometimes considered if indications fit, given its lesser effect on kidneys and bone, although it is not approved for prevention in receptive vaginal sex.
Drug interactions without the drama
Emtricitabine and tenofovir disoproxil do not heavily rely on the liver’s CYP system, which spares them from many classic interactions. That said, a few patterns matter in primary care where polypharmacy is common.
- Acid reducers like omeprazole and pantoprazole do not meaningfully change FTC/TDF levels. People can stay on them. Diuretics such as furosemide and hydrochlorothiazide, and agents that alter renal hemodynamics like lisinopril, losartan, amlodipine, and carvedilol, do not directly interact but may confound kidney monitoring. I document the baseline eGFR and keep an eye out for compounded effects. Certain antivirals like acyclovir and valacyclovir share renal tubular transport. In practice, short courses rarely cause trouble, but in a person with borderline kidney function, staggered dosing and hydration can help. Nephrotoxins deserve caution. High‑dose or frequent NSAIDs can add strain. If someone needs methotrexate, cisplatin, or IV contrast, I plan labs around those exposures. Common psychiatric medications including sertraline, escitalopram, fluoxetine, duloxetine, bupropion, quetiapine, aripiprazole, risperidone, and venlafaxine do not have clinically significant interactions with FTC/TDF. Adherence may be impacted by the mental health condition itself, not by pharmacology, so coordination with behavioral health improves outcomes. Anticoagulants such as apixaban, rivaroxaban, and warfarin, and antiplatelets like clopidogrel, can be continued. No direct interaction of concern is expected, but if illness or dehydration occurs, both kidney function and anticoagulant effects can drift.
Metformin, insulin glargine, insulin lispro, insulin aspart, dapagliflozin, empagliflozin, sitagliptin, and glipizide remain compatible. The SGLT2 inhibitors cause glycosuria and mild diuresis, so if someone reports increased urination after starting PrEP, we tease apart whether it is the diabetes regimen or a new side effect. Statins like atorvastatin, rosuvastatin, simvastatin, and pravastatin, along with antihypertensives such as lisinopril, losartan, valsartan, olmesartan, and metoprolol, can be continued, with routine attention to renal labs where relevant. Most inhalers, including albuterol, fluticasone, and budesonide, are safe. Opioid analgesics such as hydrocodone acetaminophen, tramadol, oxycodone, and morphine have no direct interaction with PrEP, but heavy use may destabilize daily routines, which can threaten adherence.
When in doubt, I check a reliable interaction database, but it is rare to find a deal‑breaker with FTC/TDF in the outpatient medication list.
Adherence in the real world
Daily medication works best when it fits the warp and weft of daily life. People with demanding shift work, caregiving responsibilities, or unstable housing can still succeed with PrEP, but the plan must respect their realities. I have seen adherence flourish when we choose a “hook” habit: brushing teeth at night, setting out a glass of water with the pill by the kettle, or pairing with breakfast. A small pill organizer with compartments for a week makes skipped days obvious.
Apple Watch taps, silent phone alarms, or calendar notifications help those who travel between time zones. If you take your dose in the evening and cross three time zones east, you can keep the home schedule for a few days, then inch toward local time. The drug’s long half‑life gives some leeway. If you forget a dose and remember within 12 hours, take it. If you remember the next day, skip the missed pill and take your regular dose. Avoid doubling up.
Some prefer on‑demand dosing when eligible. A patient I follow, a 36‑year‑old man who has sex with men, has a predictable pattern of weekend encounters. He uses the 2‑1‑1 schedule: two tablets 2 to 24 hours before sex, then one tablet 24 hours later, then another tablet 24 hours after that. He sets a series of phone alarms when he takes the first two pills, which prevents drifting off schedule. He switches to daily dosing during travel or festivals when plans turn fuzzy. Flexibility, not perfectionism, keeps him protected.
Monitoring that matters
Follow‑up visits every three months hit the right cadence for most people. We repeat HIV testing to ensure there is no breakthrough infection. We screen for STIs where they occur: throat, rectum, and urine for chlamydia and gonorrhea, plus syphilis serology. We check kidney function at least twice yearly, more often if baseline eGFR hovers near the lower limit or if other risks accumulate. Many clinics combine a quick conversation about partners, condom use, substance use, and mental health with refills, making the visit more than a lab check.
Acute HIV infection on PrEP is rare, but it does happen, usually after stopping PrEP or during stretches of poor adherence. If someone has fever, rash, sore throat, or lymph node swelling after a high‑risk exposure, I test immediately with a fourth‑generation antigen/antibody test and consider an HIV RNA test. Continuing or pausing PrEP while we sort that out depends on symptoms and timing, a decision best made with a clinician who can evaluate the specific situation.
Managing cost and access without losing continuity
Insurance policies vary. Some cover PrEP fully, others Famotidine benefits require prior authorization. Patient assistance programs can close gaps for those with high deductibles or no coverage. Disruptions often occur at pharmacy counters, not in exam rooms. I keep a short list of programs and partner pharmacies that know how to process PrEP claims. A two‑week starter supply bridges many bureaucratic delays.
If a person anticipates a gap, we plan. Say a college student returns home for the summer and changes pharmacies. We refill a month early, transfer the prescription, or arrange mail delivery timed to the move. Small logistics prevent large risks. If a gap still occurs, restart promptly and remember the lead‑in: about 7 days for anal exposure, about 21 days for vaginal exposure.
Special situations worth thinking through
For people with chronic hepatitis B who are nonadherent or who stop PrEP abruptly, hepatic flares can occur as the virus rebounds. At baseline, we check hepatitis B surface antigen and antibody status. If a person is surface antigen positive, we talk through risks and coordinate with a clinician comfortable managing HBV. If they prefer to stop PrEP later, we taper attention, not the drug, by adding closer lab follow‑up for a few months after discontinuation.
For transgender and gender diverse people, hormone therapy remains a priority. Estradiol, testosterone, spironolactone, finasteride, and dutasteride do not have clinically significant interactions with FTC/TDF. I make the point explicitly because misinformation travels fast. What does impact PrEP success is respectful care, prompt lab access, and not using clinics that force people to choose between hormone refills and sexual health services.
For adolescents and young adults, bone health and confidentiality matter. Use the smallest effective lab schedule and consider peak school schedules to reduce missed classes. A 19‑year‑old I worked with kept his PrEP in a non‑descript vitamin bottle to maintain privacy in a shared apartment. He never missed a dose once we made that simple change.
For pregnancy and the peripartum period, daily FTC/TDF PrEP is an option when HIV exposure risk is present. The conversation centers on balancing risks: the high stakes of HIV acquisition in pregnancy against the reassuring safety data for FTC/TDF. If a person on PrEP becomes pregnant, we review risk, consider continuing, and coordinate obstetric and infectious disease care. Breastfeeding discussions follow the same individualized approach.
STI dynamics and why PrEP is still the right move
It is common to see a rise in bacterial STIs in some PrEP cohorts, partly due to more frequent testing that finds asymptomatic infections. The goal is not to moralize but to minimize harm. Quarterly screening catches infections early. Doxycycline post‑exposure prophylaxis, where appropriate, can reduce syphilis and chlamydia in certain populations, though practices vary by region. Counsel on symptoms and partner notification. HIV prevention should not be paused because of a gonorrhea diagnosis; we treat the STI and keep the HIV shield in place.
Real‑world stories that shape practice
One couple, serodifferent and hoping to conceive, used a combined strategy: the partner living with HIV maintained an undetectable viral load for over six months, and the HIV‑negative partner used daily PrEP. They had unprotected intercourse during the fertile window only. Two pregnancies later, both partners remain healthy and the babies are HIV negative. Undetectable equals untransmittable, and PrEP layered on top adds confidence when life plans matter.
Another patient, a 52‑year‑old trucker with type 2 diabetes on metformin and insulin glargine, worried about keeping PrEP on board during 10‑day hauls. He placed a second bottle and a spare phone charger in a glove compartment and tied dosing to the first fuel stop after dawn. His A1c improved with more predictable routines, and his kidney function stayed stable. He has stayed on PrEP for three years without missing a refill.
A third patient struggled. She was a 28‑year‑old with simultaneous depression and alcohol use disorder, on sertraline and naltrexone. She missed labs and ran out of pills. Rather than scolding, we shifted tactics: monthly prescriptions, text reminders, and lab draws at a walk‑in site near her workplace. Six months later, adherence improved. The change was not a new drug, just a schedule that respected her bandwidth.
What to do after exposure or after stopping
PrEP prevents infection when taken around exposures, but life happens. If someone has a high‑risk exposure and has not been on PrEP or has had a recent interruption, non‑occupational post‑exposure prophylaxis should be started as soon as possible, ideally within 24 to 48 hours and up to 72 hours. That typically involves a three‑drug regimen for 28 days. After the PEP course, many transition straight to daily PrEP to avoid a protection gap. The handoff between PEP and PrEP is smoother when planned at the first PEP visit, not at day 28.
If stopping PrEP intentionally, consider timing. For anal exposure risk, continue for at least two days after the last potential exposure. For vaginal exposure or injection risk, continue for 7 days after the last exposure. People often prefer a round number, so finishing a week after the last encounter is a simple, safe rule for most.
The quiet art of making PrEP stick
The technical parts of PrEP are known. The art lies in fitting a potent prevention tool into daily routines without judgment. The best adherence plan is the one a person can see themselves living with two months from now, not the one that sounds ideal in clinic. A protective habit feels simple, almost forgettable. Refill a week early. Keep a few pills in a gym bag or wallet. Sync lab reminders with other healthcare tasks, such as a refill for lisinopril or a shot of semaglutide. If an antibiotic like azithromycin or ciprofloxacin turns up for an unrelated infection, just take it, and keep PrEP going. If life goes sideways, tell your clinician quickly. Most problems are solvable within a day.
PrEP works. Not only in clinical trials, but in the messy context of jobs, breakups, moves, and unexpected opportunities. Emtricitabine/tenofovir is a simple pill, yet it safeguards choices and relationships. The promise is not just a lower probability on a graph. It is the freedom to plan a life without fearing one mistake will define it.