Episode 213: HIV PrEP Review
H. Nicole Magaña, medical student, reviews the history of PrEP and outlines the currently FDA-approved medications used for HIV prevention. Dr. Arreaza provides additional perspective on long-acting injectable options, including how quickly they begin to protect patients after initiation.
Written by Nicole Magana, MSIV, American University of the Caribbean. Comments and edits by Hector Arreaza, MD.
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Pre-exposure prophylaxis for HIV.
Previous episodes related to HIV:
-Episode 67, HIV history (September 2021)
-Episode 68, HIV transmissibility (October 2021)
-Episode 70 (October 2021), HIV prevention (including HIV Prep with oral medications)
-Episode 98 (June 2022), we introduced Apretude, the first injectable for HIV PrEP. Apretude was approved in December 2021.
What is Pre-Exposure prophylaxis (PrEP)?
Pre-exposure prophylaxis, or PrEP, is the use of antiretroviral medications taken by individuals who are HIV-negative to prevent HIV acquisition. There are 30,000 new HIV infections annually in the US.
How effective is it?
When taken as prescribed, PrEP is highly effective at reducing the risk of HIV transmission through sexual exposure and injection drug use. Patients who are adherent to PrEP can lower their risk of contracting HIV by 99%.
The effectiveness of oral PrEP is highly adherence dependent. In trials with 70% adherence, the relative risk of HIV acquisition was 0.27, compared to 0.51 with 40-70% adherence and no significant benefit with adherence ≤40%.
How does PrEP work?
PrEP works by maintaining therapeutic drug levels in the bloodstream and in target tissues. If HIV exposure occurs, viral replication is inhibited, preventing the establishment of infection.
Brief History of PrEP.
The concept of PrEP originated from early animal studies demonstrating that antiretroviral medications could prevent retroviral transmission when administered before exposure.
In 2010, the iPrEx trial showed that daily oral tenofovir disoproxil fumarate (known as Truvada) with emtricitabine significantly reduced HIV acquisition among men who have sex with men and transgender women. This was the first large clinical trial to demonstrate the effectiveness of PrEP.
In 2012, the FDA approved oral Truvada, which is TDF/FTC (tenofovir disoproxil and emtricitabine) for HIV prevention. Since then, additional studies have expanded indications and introduced new formulations, including long-acting injectable options.
Who Should Be Offered PrEP?
PrEP should be considered for any HIV-negative individual at increased risk of HIV acquisition, including Men who have sex with men, transgender individuals, heterosexual men and women with an HIV-positive partner, individuals with recent bacterial sexually transmitted infections, people who inject drugs, individuals engaging in condomless sex with partners of unknown HIV status.
Remember that PrEP should be offered in a nonjudgmental, patient-centered manner, make it a safe space to talk openly about prevention of HIV.
Available HIV PrEP Options.
Daily Oral PrEP: There are 2 formulations of Tenofovir. There is Tenofovir disoproxil fumarate (TDF)/ Truvada and Tenofovir alafenamide (TAF)/ Descovy. Each is available in a tablet combined with Emtricitabine a nucleoside reverse transcriptase inhibitor.
Truvada: It is approved for all populations at risk through sexual exposure or injection drug use. Something to look out for before starting this medication is for pre-existing CKD. Do not give to patients who have an estimated glomerular filtration rate of less than 60 mL/min. (6)
Descovy: This option is approved for men who have sex with men and transgender women but is not approved for individuals at risk through receptive vaginal sex. It has less impact on renal function and bone mineral density compared to Truvada. It can be used in moderately reduced kidney function (GFR between 30-60 mL/min).
Truvada and Descovy are taken orally once a day.
After patients start taking these medications, when are they considered to be protected?
Nicole: With daily oral PrEP, guidelines differ with WHO and International Aids Society-USA stating it takes about 7 days, while CDC states 21 days to allow for adequate concentration in tissues (1). Adherence is critical for efficacy.
Injectable HIV PrEP.
In 2021, the FDA approved the first Injectable PrEP option Long-acting cabotegravir (CAB-LA)- known on the market as Apretude. Cabotegravir is an integrase strand transfer inhibitor administered as an intramuscular injection.Dosing consists of an initial injection, a second injection one month later, and then maintenance injections every two months (1).
Another option is Lenacapavir (Yeztugo). The Yeztugo as a pre-exposure prophylaxis (PrEP) for HIV in Oct 2024. Yeztugo is the first and only FDA-approved HIV prevention treatment that requires just two injections per year, offering a long-acting option for people who weigh at least 35kg. It is given as 2 injections every 6 months. First dose is given with 2 tablets on Day 1 and Day 2, then every 6 months 2 injections on the same day.
Clinical trials, including HPTN 083 and HPTN 084, demonstrated that injectable cabotegravir is superior to daily oral PrEP in preventing HIV infection. This advantage is largely due to improved adherence rather than differences in intrinsic drug potency.
There have been no head-to-head comparisons between Yeztugo and Apretude, but they are both very effective. Apretude starts protecting 7 days after the first dose, and Yeztugo starts protecting 2 hours after Day 2 (if patient takes the oral loading dose) or 3-4 weeks if no oral load is taken.
Injectable PrEP is particularly beneficial for patients who struggle with daily pill adherence, have trouble swallowing pills, prefer a discreet option, have difficulty storing their medication or have renal or bone disease that limits the use of tenofovir-based regimens like Truvada and Descovy (6). In one unpublished report by Medline, patients who received Apretude had an increase in bone mineral density compared to those who received Truvada (1).
Tests prior to starting PrEP.
Before initiating PrEP, patients must be confirmed to be HIV-negative. Baseline evaluation includes HIV testing with a fourth-generation antigen/antibody assay, HIV RNA testing if acute infection is suspected, renal function testing for oral PrEP, Hepatitis B screening, sexually transmitted infection screening, and pregnancy testing when appropriate. PrEP should not be started in individuals with known or suspected acute HIV infection.
Monitoring for patients on HIV PrEP.
Monitoring typically includes HIV testing every 2 to 3 months, STI screening every 3 to 6 months, renal function monitoring for those on oral PrEP (tenofovir- based), ongoing adherence and risk-reduction counseling. And for injectable PrEP, adherence to the injection schedule is essential, as delayed dosing may increase the risk of resistance if HIV infection occurs.
HIV PrEP is not a prevention for other STIs. Screening for STIs and counseling about prevention is essential.
Breakthrough HIV infections on PrEP are rare and most often associated with poor adherence or delayed diagnosis.
Truvada is more studied in all populations and is considered safe during pregnancy and breastfeeding. There is less data regarding the injectable option in patients who are pregnant, may become pregnant, or whose primary risk factor is injection drug use (1). Injectable PrEP provides an important alternative for patients with chronic kidney disease and bone disease (1).
Key Takeaway
Pre-exposure prophylaxis is a safe, effective, and evidence-based strategy for HIV prevention. With both daily oral and long-acting injectable options available, PrEP can be individualized to meet patient needs. Normalizing PrEP discussions in clinical practice is essential to reducing new HIV infections and advancing public health goals.
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References:
- Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommendations of the International Antiviral Society–USA Panel. The Journal of the American Medical Association. 2025. Gandhi RT, Landovitz RJ, Sax PE, et al.
- Long-Acting Lenacapavir Acts as an Effective Preexposure Prophylaxis in a Rectal SHIV Challenge Macaque Model. The Journal of Clinical Investigation. 2023. Bekerman E, Yant SR, VanderVeen L, et al.
- Pharmacokinetics and Safety of Once-Yearly Lenacapavir: A Phase 1, Open-Label Study. Lancet. 2025. Jogiraju V, Pawar P, Yager J, et al.
