Is pre-exposure prophylaxis (PrEP) recommended for a 30-year-old transgender female in a monogamous relationship with an Human Immunodeficiency Virus (HIV)-negative partner?

PrEP for a 30-Year-Old Transgender Female in a Monogamous Relationship with an HIV-Negative Partner

PrEP is generally not necessary for this patient if both partners are confirmed HIV-negative and the relationship is truly monogamous, but offering it remains reasonable given the high HIV incidence in transgender women populations and the possibility of undisclosed exposures. 1

Primary Recommendation Based on Current Guidelines

The most recent 2025 IAS-USA guidelines explicitly state that for monogamous sexual partners of persons with HIV who are known to be receiving ART and have viral loads below 200 copies/mL, it is reasonable to defer PrEP, though it's also reasonable to provide it if requested due to the possibility of undisclosed exposures. 1 In this case, where both partners are HIV-negative, the transmission risk is effectively zero, making PrEP medically unnecessary from a strict risk-assessment standpoint.

However, the 2025 guidelines also recommend offering PrEP to all sexually active individuals and anyone requesting it, without specific risk criteria or screening tools. 1 This serostatus-neutral approach reduces HIV stigma and acknowledges that self-reported relationship status may not always reflect actual risk exposure.

Special Considerations for Transgender Women

Transgender women face disproportionately high HIV incidence and have historically faced barriers to PrEP adherence and access. 1 The Taiwan guidelines provide strong recommendations (high-quality evidence) for PrEP use in transgender women, recognizing them as a key population at substantial risk. 1

Key factors to consider:

• Transgender women have higher rates of transactional sex, multiple partners, and condomless receptive anal intercourse compared to cisgender MSM, even when not self-reported. 2
• Only 32% of transgender women without HIV infection recently used PrEP despite 57% discussing it with providers, indicating significant implementation gaps. 3
• PrEP adherence has been historically lower in transgender women compared to MSM, with drug detection rates of only 18% in transgender women versus 52% in MSM in the iPrEx trial. 2

Clinical Decision-Making Algorithm

If the patient requests PrEP, prescribe it. 1 The 2025 guidelines explicitly support providing PrEP to anyone who requests it, acknowledging that undisclosed exposures may occur even in reportedly monogamous relationships.

If the patient does not request PrEP:

• Confirm both partners' HIV-negative status with recent testing (within past 7 days ideally). 1
• Discuss the reality of relationship dynamics and any potential for sexual activity outside the relationship. 4
• Explain that PrEP would be immediately indicated if either partner has any sexual contact outside the relationship. 4
• Offer PrEP as an option that can be started rapidly if circumstances change. 1

If PrEP Is Prescribed

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is the recommended regimen for transgender women. 1 Event-driven (2-1-1) dosing is not recommended for transgender women, as the evidence supporting this approach is limited to cisgender MSM only. 1

Pre-Initiation Requirements:

• Combined HIV antibody and antigen testing plus HIV RNA if any suspicion of acute infection. 1
• Serum creatinine with calculated creatinine clearance. 1
• Hepatitis B surface antigen (critical—see below). 1
• Hepatitis C antibody. 1
• Comprehensive STI screening (gonorrhea, chlamydia, syphilis) at all exposure sites. 1

Monitoring Schedule:

• HIV testing at 1 month, then quarterly. 1
• Creatinine clearance at first quarterly visit, then annually (more frequently if kidney dysfunction risk). 1
• Quarterly STI screening and pregnancy testing if applicable. 1

Critical Counseling Points

PrEP does not prevent other sexually transmitted infections. 1 Condoms remain essential for STI prevention regardless of PrEP use. 1

If the patient has chronic hepatitis B infection (HBsAg positive), discontinuing TDF/FTC can cause acute hepatitis flares or hepatic decompensation, particularly with cirrhosis. 1, 4 This creates a unique situation where continuing PrEP may be medically beneficial even without HIV risk, purely for HBV suppression.

Drug interactions between TDF/FTC and feminizing hormone therapy have not been adequately studied, though no clinically significant interactions are expected. 1 Reassure the patient that current evidence suggests PrEP does not interfere with gender-affirming hormone therapy. 3

Common Pitfalls to Avoid

• Do not assume monogamy equals zero risk. Studies consistently show discordance between reported and actual sexual behaviors, particularly in populations facing stigma. 2, 5
• Do not use risk-assessment tools to deny PrEP. The 2025 guidelines explicitly recommend against using specific risk criteria or screening tools as barriers to PrEP access. 1
• Do not prescribe event-driven dosing for transgender women. This regimen is only validated for cisgender MSM. 1
• Do not forget to check hepatitis B status before any discussion of discontinuing PrEP. 1, 4

Access and Retention Strategies

Transgender women who receive gender-affirming care are significantly more likely to use PrEP. 3 Integrating PrEP services with existing transgender health care improves uptake and adherence. 3 If this patient is already receiving hormone therapy or other gender-affirming care, prescribing PrEP through the same provider may improve adherence if she chooses to use it.