🧬 Pre-Exposure Prophylaxis (PrEP) Eligibility Simulator

HIV-Negative Status Confirmation — The Non-Negotiable First Checkpoint

Pre-exposure prophylaxis (PrEP) is, by design, a prevention tool for people who do not have HIV. Before a single prescription is written, a documented negative HIV test — typically a 4th-generation antigen/antibody test, sometimes paired with a nucleic acid test (NAT) if recent exposure or acute infection symptoms are suspected — is mandatory. Skipping this step is the single most consequential error in PrEP initiation.

• Ag/Ab 4th-gen: Required test type (antigen/antibody combo assay)
• ~2–4 wk: Acute infection window (NAT closes the "eclipse" gap)
• Every 3 mo: Repeat testing cadence (while on PrEP, indefinitely)
• 2: Drugs in standard oral PrEP (tenofovir + emtricitabine)

Why PrEP is inadequate treatment for existing HIV infection

Oral PrEP regimens (tenofovir disoproxil fumarate/emtricitabine, or tenofovir alafenamide/emtricitabine) and the long-acting injectable (cabotegravir) all rely on a small number of active drug classes at doses calibrated to prevent a small viral inoculum from establishing infection — not to fully suppress an already-replicating, genetically diverse viral population.

If someone with unrecognized, established HIV infection is started on a two-drug PrEP regimen, the virus is exposed to sub-suppressive drug pressure. This is a classic setup for selecting resistance mutations — particularly against emtricitabine (M184V) and, with the injectable, integrase strand-transfer inhibitor resistance. A resistant virus can then compromise future treatment options, not just for that person but potentially for onward transmission partners.

This is why every published clinical guideline — WHO, CDC, and national protocols — places a negative HIV test as an absolute prerequisite, not a formality, before the first dose of any PrEP formulation.

A PrEP prescription written without a current negative HIV test is not a smaller version of treatment — it is treatment with resistance-selecting drug pressure aimed at an undiagnosed infection. The testing checkpoint exists to prevent exactly this scenario.

The acute infection window and why timing of testing matters

Standard antigen/antibody tests can miss very recent infections during the "eclipse period" — the first 1–2 weeks after exposure, before detectable p24 antigen or antibodies appear. A person who was exposed shortly before testing could receive a negative result despite carrying an early, rapidly replicating infection.

Clinical assessment therefore includes:

• A careful history of recent exposures and any symptoms consistent with acute retroviral syndrome (fever, rash, pharyngitis, myalgia, lymphadenopathy) in the preceding weeks • Consideration of a nucleic acid test (NAT/RNA test) when recent high-risk exposure or acute symptoms raise suspicion, since NAT can detect the virus days before antibodies form • A plan to repeat HIV testing at the next visit before continuing PrEP if any uncertainty exists

Starting PrEP during unrecognized acute infection is the scenario most strongly associated with treatment-emergent resistance in real-world PrEP cohorts, which is why this checkpoint is treated as a hard gate rather than a soft recommendation.

Baseline testing as the entry point to the full PrEP visit

The baseline HIV test does not stand alone — it anchors an initial visit that typically bundles several elements together before a prescription is issued:

• Confirmed negative HIV antigen/antibody test (and NAT if acute infection is suspected) • Risk factor and exposure history (covered in Stage 2) • Renal function and hepatitis B screening (covered in Stage 4) • Counseling on formulation choice (covered in Stage 3) • Agreement on the follow-up monitoring schedule (covered in Stage 5)

Organizing PrEP initiation around this sequence — test first, assess risk, choose formulation, check labs, schedule monitoring — is what turns PrEP from a single prescription into a structured, ongoing prevention program.

Risk Factor Assessment — Identifying Who Benefits Most from PrEP

PrEP eligibility is not a yes/no biological test — it is a clinical judgment built from behavioral and epidemiological risk factors, each of which independently raises the probability of HIV exposure. Guidelines list specific factors to screen for explicitly, because identifying even one substantially shifts the risk-benefit calculation in favor of starting PrEP.

• 4: Core risk factors screened (behavioral + epidemiological)
• Key factor: Condomless sex, unknown status (partner HIV status unknown/positive)
• Key factor: Shared injection equipment (needle/syringe/works sharing)
• Key factor: Recent bacterial STI (marker of condomless exposure)

The four risk factors that drive a PrEP recommendation

Clinical risk assessment for PrEP typically screens explicitly for:

1. Condomless sex with a partner of unknown or HIV-positive status: the single most commonly cited indication. "Unknown status" is treated the same as "positive" for risk purposes, because status cannot be assumed.

2. Injection drug use with shared needles, syringes, or other injection equipment: blood-to-blood contact through shared works is an efficient transmission route independent of sexual activity, and is assessed separately from sexual history.

3. A recent bacterial sexually transmitted infection (e.g., syphilis, gonorrhea, chlamydia): a recent STI diagnosis is not itself an HIV risk factor biologically alone — it is a strong behavioral marker that condomless sex occurred, and some STIs (particularly ulcerative ones like syphilis) also biologically increase susceptibility to HIV acquisition.

4. A partner with a detectable HIV viral load: for couples where one partner is living with HIV, PrEP for the HIV-negative partner is recommended whenever the partner's viral load is not durably undetectable — since "undetectable = untransmittable" (U=U) only holds once suppression is confirmed and sustained.

None of these four factors is required in isolation for PrEP to be appropriate — but each one identified raises the clinical benefit, and the presence of multiple factors together moves a candidate from "consider PrEP" to "strongly recommended."

Risk assessment is a conversation, not a checklist alone

Because sexual and drug-use history are sensitive topics, effective risk assessment relies on non-judgmental, direct questioning rather than assumptions based on demographic group. Guidelines explicitly caution against limiting PrEP counseling to specific populations by assumption (e.g., offering it reflexively to some groups while failing to ask other patients directly) — risk factors, not identity categories, should drive the conversation.

Practical assessment typically covers:

• Number and HIV status of recent sexual partners, and consistency of condom use • History of injection drug use and any equipment sharing, including non-prescribed substances • STI testing history and any diagnoses in the past 6–12 months • Relationship structure — including serodifferent partnerships and whether the partner living with HIV is on suppressive treatment • Anticipated future exposure patterns, since PrEP is also appropriate for anticipated risk, not only past exposure

From risk factors to a candidacy recommendation

Translating identified risk factors into a recommendation follows a simple gradient used throughout this simulator:

• Zero identified risk factors: PrEP is not indicated — the discussion shifts to periodic reassessment, since risk can change over time • One identified risk factor: PrEP should be discussed and offered — "consider PrEP," with shared decision-making about formulation and adherence • Two or more identified risk factors: PrEP is strongly recommended — the cumulative epidemiological risk clearly outweighs the low absolute risk of medication side effects

This is a simplified illustrative gradient for teaching purposes; real clinical decisions also weigh local HIV prevalence, patient preference, and anticipated adherence.

Formulation Options — Daily Oral, On-Demand, or Long-Acting Injectable

Once a candidate is identified, PrEP is not a single product — it is a menu of three delivery approaches, each trading off adherence burden, dosing complexity, and applicability to different populations and exposure patterns. Matching the formulation to the person's life is often what determines whether PrEP actually prevents infection in practice.

• 1×/day: Daily oral tablet (tenofovir-based, continuous)
• Event-driven: "2-1-1" on-demand (around anticipated exposure)
• Every 2 mo: Long-acting injectable (cabotegravir, intramuscular)
• Varies: Adherence demand (lowest for injectable, event-timing for 2-1-1)

Daily oral tablet — the original and most widely available option

Daily oral PrEP (tenofovir disoproxil fumarate/emtricitabine, or tenofovir alafenamide/emtricitabine) remains the most studied and most broadly available formulation worldwide. Taken once per day regardless of sexual activity, it reaches protective tissue drug concentrations after a loading period — full protection for receptive anal sex is generally reached faster than for receptive vaginal sex, which is one reason daily dosing (rather than on-demand) is preferred for people at risk through vaginal or frontal sex.

Advantages: broadest population applicability, well-established long-term safety data, easily paused and restarted, low cost relative to injectable formulations, wide generic availability.

Challenges: requires consistent daily adherence indefinitely regardless of whether exposure occurs that day, which for some people is harder to sustain than event-driven dosing.

On-demand "2-1-1" dosing — event-driven protection for specific populations

The "2-1-1" regimen was developed and validated specifically for cisgender men and transgender women who have sex with men, around anticipated sexual activity:

• 2 pills taken 2–24 hours before sex • 1 pill taken 24 hours after the first dose • 1 more pill taken 24 hours after that (total of 4 pills around a single sexual event, or continued daily-style dosing for ongoing frequent activity)

This approach reduces total pill burden for people with predictable, infrequent exposure, and has demonstrated strong efficacy in the population it was studied in. It is not currently recommended for people at risk through receptive vaginal or frontal sex, where tissue drug levels take longer to reach protective concentrations — daily dosing remains preferred there.

On-demand dosing requires the ability to anticipate sexual activity in advance, which makes it less suitable for unplanned or unpredictable exposure patterns.

"2-1-1" dosing is validated for specific populations and exposure routes only — the formulation decision is not purely a matter of preference but must match the person's anatomy and predictability of exposure.

Long-acting injectable — maximal adherence forgiveness, every two months

Long-acting injectable cabotegravir, administered as an intramuscular injection every two months after an initial loading phase, removes daily pill-taking from the equation entirely. For people who struggle with daily adherence — a well-documented driver of real-world PrEP failure despite near-100% efficacy in clinical trials with perfect adherence — the injectable offers a fundamentally different adherence profile.

Advantages: no daily pill, discreet dosing interval, strong efficacy data, well suited to people who have struggled with oral adherence.

Considerations: requires clinic visits every two months rather than a pharmacy refill, has a long "tail" of low drug concentrations after discontinuation that could theoretically favor resistance if HIV is acquired near the end of the dosing interval, and is not yet as universally available or affordable as oral formulations.

Formulation choice is ultimately a shared decision: same candidacy, different regimen, matched to what the person can realistically sustain over months and years.

Renal Function & Baseline Labs — Screening Before the First Dose

Confirming HIV-negative status and identifying risk factors establishes that PrEP is appropriate — but two additional baseline checks determine how safely it can be started: kidney function and hepatitis B status. Both influence which formulation is safe and what monitoring is needed once treatment begins.

• <60 mL/min: eGFR threshold of concern (triggers caution / alternative)
• 4: Labs drawn at baseline (eGFR, HBsAg, HIV test, creatinine)
• Flare risk: Why hepatitis B matters (on stopping active anti-HBV drugs)
• Ongoing: Renal recheck cadence (reassessed at monitoring visits)

Why kidney function is checked before oral PrEP

Tenofovir — the backbone drug shared by both oral PrEP formulations — is cleared by the kidneys and has a well-documented, generally small but real, effect on renal tubular function. Before starting oral PrEP, estimated glomerular filtration rate (eGFR) is calculated from a baseline serum creatinine to confirm the kidneys can safely handle and clear the drug.

As a general threshold used in this simulator: eGFR at or above 60 mL/min is considered adequate for standard oral formulations without special adjustment. Below that threshold, clinicians exercise caution — some oral formulations are not recommended, others may require dose adjustment or more frequent renal monitoring, and the long-acting injectable (which does not depend on the same renal clearance pathway) may become the preferred alternative.

This is not a hard universal cutoff for every formulation and guideline — thresholds and recommended actions vary by specific drug and local protocol — but the underlying principle is consistent: renal function must be known before the first dose, not discovered afterward.

Reduced eGFR does not automatically disqualify someone from PrEP altogether — it redirects the formulation decision, since the long-acting injectable pathway is not renally dependent in the same way as oral tenofovir-based regimens.

Hepatitis B screening — the second essential baseline test

Both oral PrEP drug backbones are also active against hepatitis B virus (HBV) — tenofovir is, in fact, a standard treatment for chronic hepatitis B. This creates an important, often under-recognized safety issue: if someone with undiagnosed chronic HBV infection starts PrEP and later stops it, they lose HBV-suppressive drug pressure abruptly, which can trigger a hepatitis flare — sometimes severe.

Baseline hepatitis B surface antigen (HBsAg) testing therefore serves two purposes:

• Identifying anyone with active HBV infection, so that stopping PrEP later can be planned and monitored appropriately (or so that HBV-specific care is coordinated) • Informing vaccination: people without evidence of HBV immunity are typically offered hepatitis B vaccination as part of the same visit

This baseline screen is a good example of how PrEP initiation intersects with, and can improve, overall preventive care beyond HIV alone.

The complete baseline lab panel

Put together, the baseline visit typically includes:

• HIV antigen/antibody test (Stage 1) — confirms negative status • Serum creatinine and calculated eGFR — establishes renal baseline and formulation suitability • Hepatitis B surface antigen (and often hepatitis B core antibody / surface antibody) — screens for active or past infection and immunity status • STI testing (syphilis, gonorrhea, chlamydia) — establishes a baseline and supports the risk assessment from Stage 2 • Pregnancy testing, where relevant, to inform formulation counseling

All of this is gathered before or at the same visit as the first prescription, so that formulation choice (Stage 3) and the monitoring plan (Stage 5) are built on complete information rather than assumptions.

Ongoing Monitoring Schedule — The Recurring Cadence That Makes PrEP Work

PrEP is not a one-time prescription — it is an ongoing program of care. Once started, guidelines call for periodic HIV testing, renal function monitoring, and STI screening at regular intervals, most commonly every three months for oral formulations. This recurring schedule is what catches breakthrough infections early, tracks emerging side effects, and keeps the regimen matched to the person's evolving risk and health status.

• 3 months: Typical oral PrEP interval (HIV test + STI screen + labs)
• Required: HIV testing at each visit (before continuing prescription)
• Periodic: Renal monitoring frequency (especially if baseline eGFR low)
• Every visit: STI screening frequency (often 3-site testing)

Why repeat HIV testing every visit is non-negotiable

Every follow-up visit begins the same way Stage 1 did: with a current HIV test, before the next supply of PrEP is prescribed. This is not redundant paperwork — it directly protects against the same resistance-selection risk described in Stage 1. If a breakthrough infection occurred despite PrEP (rare, but documented, particularly with inconsistent adherence or, even more rarely, with drug-resistant virus), continuing the same regimen unchanged would again apply sub-suppressive drug pressure to an active infection.

Repeat testing at each visit, most commonly every three months for oral PrEP, is therefore the mechanism that catches this scenario early — typically before extensive resistance can develop — and triggers a switch to full combination antiretroviral treatment if a breakthrough infection is identified.

The three-month interval is not arbitrary — it balances practical visit burden against the goal of detecting any breakthrough infection early enough to prevent both drug resistance and onward transmission.

Renal function and other laboratory monitoring over time

For people on oral tenofovir-based PrEP, renal function is rechecked periodically after the baseline assessment described in Stage 4 — more frequently for anyone with a lower baseline eGFR, older age, or other renal risk factors, less frequently for those with normal baseline function and no risk factors. This ongoing surveillance is what allows early detection of any drug-related decline in kidney function, well before it becomes clinically significant, and can prompt a switch in formulation if needed.

For the long-acting injectable, monitoring shifts focus somewhat — renal labs are less central, but injection-site reactions and adherence to the every-two-month visit schedule become the operational focus, since a missed or delayed injection creates a window of declining drug levels.

STI screening as an integrated part of every PrEP visit

Because many people on PrEP remain sexually active with variable partner status — indeed, that is often part of why PrEP was recommended in the first place — routine STI screening (commonly three-site testing for gonorrhea and chlamydia, plus syphilis serology) is bundled into the same recurring visit as HIV testing and renal monitoring.

This integration serves two purposes: it catches and treats STIs promptly (reducing further transmission and reinforcing the risk-assessment loop from Stage 2), and it reinforces PrEP as a comprehensive sexual health service rather than a narrow HIV-only intervention.

Taken together, the recurring cycle — HIV test, renal check, STI screen, adherence and side-effect discussion, formulation reassessment — is what transforms PrEP from a single prescribing decision into a sustained prevention program capable of delivering the high real-world effectiveness seen with consistent use.