12.1 Sexual Health Counseling & Risk-Reduction Strategies

Comprehensive Sexual History: The CDC 5 P's Framework

A thorough, non-judgmental sexual history is fundamental to primary care preventive medicine. It identifies risks for sexually transmitted infections (STIs), human immunodeficiency virus (HIV), unplanned pregnancies, and sexual dysfunction. The Centers for Disease Control and Prevention (CDC) formalizes this assessment through the 5 P's framework:

1. Partners:
   • Inquiry: Assess the gender, biological sex, and number of sexual partners over defined time horizons (past 2 to 3 months and past 12 months).
   • Clinical Phrasing: "In the past 12 months, how many sexual partners have you had? Are your partners men, women, nonbinary individuals, or all of the above?"
   • Risk Stratification: Assess concurrent partnerships, partners with known HIV/STIs, or partners with injection drug exposure.
2. Practices:
   • Inquiry: Clarify specific sexual acts to guide anatomical site-specific screening (pharyngeal, urogenital, rectal).
   • Clinical Phrasing: "To help me decide which lab tests are appropriate, what specific sexual acts do you engage in? Do you engage in oral sex, vaginal sex, or anal sex? Are you the insertive partner, receptive partner, or both?"
   • Clinical Significance: More than 70% of extragenital gonococcal and chlamydial infections are asymptomatic and completely missed if clinicians only obtain urine samples.
3. Protection from STIs:
   • Inquiry: Determine the frequency and consistency of barrier method use.
   • Clinical Phrasing: "How often do you use barrier methods such as external condoms, internal condoms, or dental dams? Do you use them all the time, sometimes, or never? In what situations do you use protection?"
   • Harm Reduction: Inquire about lubricant use (water-based or silicone lubricants are compatible with latex; oil-based products compromise latex integrity, resulting in condom rupture).
4. Past History of STIs:
   • Inquiry: Document historical STI diagnoses, completed treatments, and recurrence patterns.
   • Clinical Phrasing: "Have you ever been diagnosed with or treated for a sexually transmitted infection such as chlamydia, gonorrhea, syphilis, herpes, trichomoniasis, or HPV? Has any partner notified you of an STI?"
   • Epidemiological Correlation: A prior bacterial STI within the preceding 6 to 12 months is one of the strongest independent clinical predictors of future STI acquisition and HIV seroconversion.
5. Prevention of Pregnancy / Pleasure:
   • Reproductive Life Plan: "Do you or your partner have plans or desire for pregnancy now or in the future? What methods are you currently using to prevent pregnancy?"
   • Dual Protection: Emphasize that highly effective reversible contraceptives (e.g., intrauterine devices, subdermal implants, oral contraceptives) provide zero protection against STIs and HIV; condoms must be combined with systemic contraception for comprehensive risk reduction.
   • Sexual Satisfaction & Pleasure: Assess sexual function, pain (dyspareunia), erectile dysfunction, libido, and lubrication. Clinicians should ensure discussions are sex-positive and trauma-informed.

---

LGBTQ+ Affirming Care & Inclusive Practice

Creating an affirming, clinically competent environment for lesbian, gay, bisexual, transgender, queer, and gender-diverse (LGBTQ+) patients is essential to eliminate health disparities and build therapeutic trust.

Inclusive Clinical Communication & Etiquette

• Pronouns and Chosen Names: Standard intake paperwork and verbal introductions should invite patients to share their pronouns (e.g., she/her, he/him, they/them) and chosen name, which may differ from their legal name or electronic medical record identifier.
• Neutral, Non-Heteronormative Language: Use open-ended phrasing. Ask "Are you in a relationship?" or "Do you have a partner or partners?" rather than presuming marital status, sexual orientation, or the gender of partners.
• Organ Inventory Approach: In transgender and gender-diverse patients, clinicians must never make assumptions regarding anatomical structures based on gender presentation or identity. Conduct an explicit organ inventory: document the presence or absence of breasts, cervix, uterus, ovaries, prostate, testes, neovagina, or neopenis. Clinical screening rules follow anatomy: anyone with an intact cervix requires cervical cancer screening, and anyone with a prostate requires age-appropriate prostatic assessment.
• Patient-Affirmed Terminology: Clarify terms the patient prefers for their genitalia during examinations (e.g., "external genitalia," "frontal opening," "chest tissue").
• Gender-Affirming Hormone Therapy (GAHT) Considerations:
  • Masculinizing Therapy (Exogenous Testosterone): Induces amenorrhea and endometrial atrophy but does not reliably suppress ovulation; pregnancy can still occur. AFAB patients on testosterone engaging in penile-vaginal intercourse require effective non-estrogenic contraception (e.g., levonorgestrel IUD, copper IUD, depot medroxyprogesterone acetate, or etonogestrel subdermal implant).
  • Feminizing Therapy (Exogenous Estrogen + Antiandrogens): Induces testicular atrophy and reduces spermatogenesis, but is not a reliable contraceptive. AMAB patients engaging in insertive sex with partners who can become pregnant must be counseled on barrier methods or partner contraception.
  • Drug-Drug Interactions with PrEP: Tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), emtricitabine (FTC), and cabotegravir have no clinically significant pharmacokinetic interactions with feminizing (estradiol, spironolactone) or masculinizing (testosterone) gender-affirming regimens. Patients should be reassured that PrEP does not diminish the clinical efficacy or blood levels of their hormones.

---

HIV Pre-Exposure Prophylaxis (PrEP): USPSTF Grade A Recommendations

HIV Pre-Exposure Prophylaxis (PrEP) involves the administration of antiretroviral medications to HIV-negative individuals at high risk of HIV acquisition. The United States Preventive Services Task Force (USPSTF) issues a Grade A recommendation that clinicians offer PrEP with effective antiretroviral therapy to persons at high risk of HIV acquisition.

Clinical Indications for PrEP

According to CDC and USPSTF guidelines, PrEP is indicated for sexually active adolescents and adults (weight >=35 kg) and persons who inject drugs (PWID) meeting any of the following criteria within the preceding 6 months:

1. Men Who Have Sex with Men (MSM) and Transgender Women:
   • Any condomless anal sex (receptive or insertive) with a partner whose HIV status is unknown or positive (with a detectable or unknown viral load).
   • Diagnosis of a bacterial STI (chlamydia, gonorrhea, or syphilis) within the past 6 months.
2. Heterosexually Active Men and Women:
   • Condomless sex with a partner living with HIV who has a detectable or unknown viral load.
   • Inconsistent condom use with partners belonging to populations with high HIV prevalence (e.g., PWID, incarcerated persons, bisexual men).
   • Diagnosis of gonorrhea or syphilis within the past 6 months.
3. Persons Who Inject Drugs (PWID):
   • Sharing of injection drug equipment, needles, syringes, cookers, or cotton.
   • Engaging in transactional sex or condomless sex alongside injection drug use.

---

FDA-Approved PrEP Regimens: Comparative Pharmacology

Currently, three antiretroviral regimens are FDA-approved for HIV pre-exposure prophylaxis in the United States:

Clinical Deep-Dive: TDF/FTC vs. TAF/FTC

• Tenofovir Disoproxil Fumarate (TDF) is an acyclic nucleotide diester prodrug. Following oral ingestion, TDF is rapidly cleaved in plasma into free tenofovir, resulting in high circulating systemic tenofovir concentrations before intracellular entry. This high circulating load interacts with organic anion transporters (OAT1/OAT3) in the renal proximal convoluted tubule, potentially inducing mitochondrial DNA depletion, proximal tubular dysfunction (Fanconi syndrome with glucosuria, phosphaturia, aminoaciduria), and accelerated bone mineral turnover.
• Tenofovir Alafenamide (TAF) is a targeted phosphonamidate prodrug. TAF remains intact and highly stable in systemic circulation, resulting in >90% lower plasma tenofovir concentrations while delivering 4- to 7-fold higher intracellular active tenofovir diphosphate concentrations within target peripheral blood mononuclear cells (PBMCs) and lymphoid tissue. This translates into minimal nephrotoxicity and preservation of bone mineral density.
• CRITICAL BOARD EXAM PEARL: The Receptive Vaginal Exclusion for TAF/FTC: The landmark Phase 3 DISCOVER trial evaluated the non-inferiority of TAF/FTC compared to TDF/FTC exclusively in cisgender MSM and transgender women having condomless receptive anal intercourse. The trial explicitly did not enroll cisgender women or individuals engaging in receptive vaginal sex. Furthermore, pharmacokinetic studies indicate that active tenofovir diphosphate concentrations in cervical and vaginal mucosal tissues are markedly lower with TAF than with TDF. Consequently, TAF/FTC (Descovy) is NOT FDA-approved or guideline-endorsed for individuals at risk of HIV acquisition through receptive vaginal intercourse. In a cisgender female seeking oral PrEP, TDF/FTC (Truvada) is the only approved oral regimen!

Long-Acting Injectable Cabotegravir (Apretude)

• Mechanism: Long-acting formulation of cabotegravir, an integrase strand transfer inhibitor (INSTI) that binds the integrase active site, blocking the strand transfer step of retroviral DNA integration into host chromatin.
• Administration: Administered as a 600-mg (3-mL) deep gluteal intramuscular injection. Initiated with two consecutive monthly loading doses (Month 1 and Month 2), followed by injections every 2 months (every 8 weeks).
• Oral Lead-in Option: An optional 4-week oral cabotegravir lead-in (30 mg once daily) may be used to assess drug tolerability prior to receiving the depot injection; however, CDC guidelines endorse direct-to-injection initiation without oral lead-in based on trial safety data.
• Superior Clinical Efficacy: In randomized trials, long-acting cabotegravir demonstrated superior efficacy over daily oral TDF/FTC, reducing HIV transmission by 66% in cisgender MSM and transgender women (HPTN 083) and by 88% in cisgender women (HPTN 084). The superior efficacy was primarily attributable to overcoming the adherence challenges inherent to daily oral regimens.
• Injection Window and Oral Bridging: Injections must occur within a window of 7 days before to 7 days after the scheduled 2-month injection date. If a patient expects to miss an injection by more than 7 days, daily oral cabotegravir (30 mg daily) or daily oral TDF/FTC must be prescribed as oral bridging therapy starting 2 months after the last injection and continuing until injections are resumed.

Event-Driven ("2-1-1" or "On-Demand") Oral PrEP

• The Regimen: Taking 2 tablets of TDF/FTC 2 to 24 hours before anticipated sex, followed by 1 tablet 24 hours after the initial double dose, and 1 tablet 48 hours after the initial double dose (the IPERGAY protocol).
• Candidate Restrictions: The CDC and international guidelines endorse 2-1-1 dosing strictly for adult cisgender MSM engaging exclusively in anal intercourse who have infrequent sexual encounters and can anticipate sex at least 2 hours in advance.
• STRICT CONTRAINDICATIONS to 2-1-1 Dosing:
  • Cisgender women and all individuals engaging in receptive vaginal sex (vaginal mucosal drug saturation requires at least 21 days of daily dosing; 2-1-1 yields subtherapeutic vaginal tissue levels).
  • Transgender men having vaginal intercourse.
  • Persons who inject drugs (PWID).
  • Individuals with chronic Hepatitis B infection (intermittent dosing leads to inadequate HBV suppression and severe rebound viremia/hepatic flare).
  • Patients taking TAF/FTC (Descovy is not studied or approved for 2-1-1 dosing).

---

Mandatory Pre-PrEP Screening Protocol

Initiating PrEP without rigorous screening can lead to disastrous consequences, most notably the rapid emergence of antiretroviral drug resistance if PrEP is inadvertently initiated in a patient harboring undiagnosed, acute HIV infection.

Required Baseline Laboratory Testing Checklist

1. HIV Diagnostic Testing (Documentation of Negative Status):
   • Must document a negative laboratory-based HIV-1/2 4th-generation antigen/antibody (Ag/Ab) immunoassay within 7 to 14 days prior to starting or refilling PrEP.
   • Acute Retroviral Syndrome Assessment: Inquire about any viral syndrome (fever, pharyngitis, adenopathy, rash, myalgias) or condomless exposure within the past 14 to 30 days. If acute retroviral syndrome is suspected or if the patient received post-exposure prophylaxis (PEP) within the preceding 30 days, a plasma HIV-1 RNA NAAT (viral load) must be ordered concurrently, as the viral RNA test has the shortest window period (detectable within 10 to 12 days).
   • Exam Rule: Never initiate PrEP based solely on an oral fluid rapid test or if an HIV test is pending. If HIV status is indeterminate or positive, withhold PrEP and refer immediately for fully suppressive antiretroviral therapy.
2. Renal Function (Serum Creatinine and eGFR):
   • Required for oral TDF/FTC (must have eGFR >=60 mL/min) and oral TAF/FTC (must have eGFR >=30 mL/min). Baseline urinalysis to check for proteinuria/glucosuria is recommended.
3. Hepatitis B Virus (HBV) Serology (HBsAg, anti-HBs, anti-HBc):
   • Both TDF and TAF, as well as emtricitabine, are highly active against Hepatitis B virus polymerase.
   • The Hep B Flare Warning: If a patient with chronic Hepatitis B (HBsAg-positive) starts TDF/FTC or TAF/FTC, their HBV replication is suppressed. However, if the patient subsequently discontinues PrEP abruptly (e.g., due to loss of insurance, side effects, or changes in sexual activity), severe, life-threatening acute hepatitis exacerbations (flares) and fulminant hepatic failure can occur due to sudden HBV rebound. In HBsAg-positive patients, PrEP should be co-managed with a hepatologist, and if PrEP is discontinued, continuation of alternate anti-HBV therapy (such as entecavir) or intensive clinical hepatic monitoring is mandatory.
   • If the patient is seronegative (HBsAg, anti-HBs, and anti-HBc all negative), administer the complete Hepatitis B vaccine series.
4. Baseline Sexually Transmitted Infection (STI) Screening:
   • Perform multi-site Nucleic Acid Amplification Testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae (pharyngeal swab, rectal swab, and first-catch urine / vaginal swab) regardless of symptoms.
   • Serologic screening for Treponema pallidum (syphilis) using non-treponemal or treponemal assays.
5. Lipid Panel:
   • Required prior to initiating TAF/FTC due to potential elevations in total cholesterol, LDL, and triglycerides.
6. Pregnancy Testing:
   • Urine human chorionic gonadotropin (hCG) in individuals of childbearing potential. TDF/FTC is preferred and established as safe during pregnancy and lactation.

---

Longitudinal On-PrEP Monitoring Schedule

PrEP requires ongoing clinical surveillance to ensure continued HIV negativity, monitor renal safety, and treat asymptomatic STIs promptly:

Every 3 Months (All Patients on PrEP)

• HIV-1/2 4th-generation Ag/Ab immunoassay: Repeat testing is mandatory prior to issuing a 90-day medication refill.
• HIV-1 RNA NAAT: Recommended by CDC for all patients on long-acting cabotegravir at every 2-month injection visit. Cabotegravir can delay antibody production during breakthrough infections; RNA testing detects early virologic breakthrough and prevents the selection of INSTI-resistant viral strains.
• Symptom Review: Screen for symptoms of acute retroviral syndrome or medication side effects.
• Adherence & Behavioral Risk Counseling: Evaluate adherence, pill counts, missed doses, and discuss harm reduction.
• Pregnancy Testing: Repeat urine hCG for individuals with childbearing potential.

Every 6 Months

• Multi-Site STI Screening: Repeat chlamydia and gonorrhea NAAT at all anatomical sites of sexual exposure (pharyngeal, rectal, urogenital), plus serologic testing for syphilis, regardless of symptoms.
• Renal Function (eGFR): Repeat serum creatinine/eGFR for individuals taking oral TDF/FTC who are aged >=50 years or whose baseline eGFR was <90 mL/min.

Every 12 Months

• Renal Function (eGFR): For all other patients taking oral TDF/FTC or TAF/FTC (e.g., age <50 with baseline eGFR >=90 mL/min).
• Fasting Lipid Profile: For patients taking TAF/FTC.
• Comprehensive Clinical Reassessment: Evaluate whether PrEP remains indicated based on the patient's ongoing sexual and substance use behaviors.

---

Post-Exposure Prophylaxis (PEP): Occupational & Non-Occupational (nPEP)

Post-Exposure Prophylaxis (PEP) is an emergency antiretroviral regimen administered to prevent HIV infection following an isolated, high-risk exposure to blood or body fluids (e.g., accidental needlestick, broken condom during sex with an HIV-positive partner, sexual assault, sharing injection equipment).

The Critical 72-Hour Window

• Initiation Timeline: PEP must be started as soon as possible following exposure—ideally within 2 hours, and no later than 72 hours (3 days) post-exposure.
• Biological Basis: Animal models prove that HIV takes approximately 48 to 72 hours to replicate within dendritic cells and travel to regional lymph nodes. Once systemic lymphatic dissemination occurs, antiretroviral prophylaxis fails. If a patient presents >72 hours after exposure, PEP is not effective and not recommended; the patient should instead undergo baseline testing and close clinical monitoring.
• Duration of Therapy: PEP must be taken consistently for exactly 28 days.

Recommended PEP Regimens (CDC Guidelines)

For adults and adolescents with normal renal function (eGFR >=60 mL/min), the preferred regimen consists of a 3-drug combination incorporating a dual-NRTI backbone plus a high-barrier integrase strand transfer inhibitor (INSTI):

1. Dual-NRTI Backbone:
   • Tenofovir disoproxil fumarate (TDF) 300 mg / Emtricitabine (FTC) 200 mg (Truvada) PO once daily. (If eGFR is 30 to 59 mL/min: adjust TDF/FTC dosing interval or substitute Tenofovir alafenamide / emtricitabine [Descovy] PO once daily).
2. PLUS an Integrase Strand Transfer Inhibitor (INSTI):
   • Dolutegravir (Tivicay) 50 mg PO once daily, OR
   • Raltegravir (Isentress) 400 mg PO twice daily (or Raltegravir HD 1200 mg PO once daily).
3. Alternative Approved Regimen:
   • Bictegravir 50 mg / Emtricitabine 200 mg / Tenofovir alafenamide 25 mg (Biktarvy) PO once daily as a single-tablet 3-drug regimen.

Laboratory Testing Cascade for PEP

• Baseline Testing (Day 0): HIV-1/2 4th-generation Ag/Ab test, Hepatitis B serologies (HBsAg, anti-HBs, anti-HBc), Hepatitis C antibody, baseline serum creatinine/eGFR, urine pregnancy test, and baseline STI screening (chlamydia, gonorrhea, syphilis). Crucial: Do not delay the first dose of PEP while waiting for baseline laboratory results.
• Follow-up Testing: Repeat HIV Ag/Ab immunoassay at 4 to 6 weeks post-exposure (immediately upon completing the 28-day regimen) and at 12 weeks post-exposure.
• Transitioning from PEP to PrEP: If a patient completing a 28-day course of PEP has ongoing, persistent sexual or injection drug behaviors that confer high risk for HIV, they should be transitioned immediately to PrEP without any gap in medication coverage, provided their 4th-generation HIV test at day 28 is confirmed negative.