**Background:** HIV preexposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition and is a critical component of the Ending the HIV Epidemic initiative's 'prevent' pillar, which aims for 50% PrEP coverage among people with indications by 2025. However, only 30% of people with PrEP indications received a prescription in 2021. The cost of PrEP medication, clinical visits, and laboratory testing has been identified as a key barrier. Since a 2015 analysis estimated approximately 90,000 people had uncovered costs, the landscape has changed significantly: the US Preventive Services Task Force issued a grade A recommendation for oral PrEP in 2019, the Affordable Care Act required most private insurance plans and Medicaid expansion programs to cover PrEP without cost sharing as of January 2021, generic tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) was introduced in 2021, and state and federal PrEP assistance programs were launched. This study aimed to update estimates of uncovered PrEP costs under 2021 guideline and coverage conditions.
**Methods:** The authors used a framework similar to the prior 2015 analysis by Smith and colleagues to identify people with uncovered costs for PrEP medication and clinical care. Population inputs came from the National HIV Surveillance System, National Health and Nutrition Examination Survey, and census data to estimate the number of adults aged 18+ with PrEP indications in 2018 (n=1,216,210), stratified by HIV transmission risk group: men who have sex with men (MSM), heterosexual men and women, and people who inject drugs (PWID). Insurance status and federal poverty level data were derived from the 2017–2019 National Survey of Family Growth and the 2019 National Survey on Drug Use and Health. For insured people, the authors estimated 1% would have a PrEP prescription denied by insurance. For uninsured people, 13% were estimated ineligible due to immigration status and 8% fell into the Medicaid coverage gap. People without PrEP insurance coverage and income <500% of federal poverty level were classified as having uncovered costs for clinical care only (eligible for manufacturer medication assistance), while those with income ≥500% of poverty had uncovered costs for both medication and clinical care. Cost inputs included net Medicaid prices for brand-name Truvada and Descovy, National Average Drug Acquisition Cost for generic TDF/FTC, CMS 2021 Medicare Physician Fee Schedule for clinical visits, and CMS 2021 Clinical Laboratory Fee Schedule for lab tests. Sensitivity analyses varied key inputs including poverty level percentages, medication costs, and a scenario without medication assistance programs.
**Key Results:** Among 1,216,210 US adults with PrEP indications in 2018, 63.6% had private insurance, 20.6% had public insurance, and 15.5% were uninsured. Insurance coverage varied substantially by risk group: 70.9% of MSM had private insurance versus 17.6% of PWID; 59.7% of PWID had public insurance. An estimated 49,860 people (4% of those with indications) had uncovered costs for PrEP: 32,350 MSM (4% of MSM), 7,600 heterosexual women (4%), 5,070 heterosexual men (6%), and 4,840 PWID (6%). Of these, 3,160 (6%) had uncovered costs for both medication and clinical care ($18.9 million annually), while 46,700 (94%) had uncovered costs for clinical care only ($83.5 million annually). The total annual uncovered cost was $102.4 million ($13.3 million for medication, $33.5 million for clinical visits, $55.7 million for laboratory testing). Per-person annual costs ranged from $5,345 (heterosexual men and women) to $6,325 (MSM) for medication and clinical care combined, and from $1,149 to $2,129 for clinical care only. Sensitivity analyses showed total annual uncovered costs ranging from $99.4 million to $105.7 million when varying poverty level inputs, increasing to $128.6 million using a secondary medication price source, and rising to $298.3 million in a scenario without medication assistance programs.
**Clinical Implications:** Compared to the 2015 analysis, the estimated number of people with uncovered PrEP costs decreased by 47% (from 93,630 to 49,860) and total annual uncovered costs decreased by more than 50% (from approximately $208 million to $102 million). Key drivers included insurance coverage gains from ACA implementation and Medicaid expansion, a higher proportion of uninsured people with incomes below 500% of poverty (making them eligible for medication assistance), and the introduction of generic TDF/FTC reducing annual medication costs from $10,770 (Truvada only in 2015) to $4,196 (weighted average in 2018). The authors note that 79% of uninsured adults with PrEP indications were eligible for health insurance coverage through ACA Marketplaces, Medicaid, or employer-sponsored plans. However, significant racial, ethnic, and geographic inequities in PrEP use persist, particularly in the southern US where 97% of the 2.2 million adults in the Medicaid coverage gap reside. The study likely overestimates real-world costs by assuming 100% PrEP uptake among those with uncovered costs, whereas actual PrEP coverage was only 30% in 2021. The findings are intended to inform ongoing policy discussions about establishing a national PrEP assistance program, with the authors noting that more than $100 million annually would be significant but represents a small fraction of the approximately $28 billion in total domestic HIV spending (of which prevention accounts for ~$900 million).