Pre-exposure prophylaxis, better known as PrEP, has transformed HIV prevention over the last decade or more. PrEP is not one specific medicine, but a medication regimen designed to prevent HIV. The first medication approved for HIV prevention in 2012, Truvada, has since been joined by Descovy and in the last few years two injectable options, one which lasts for 2 months, Apretude and a new option that lasts for 6 months, Yeztugo. While PrEP is often targeted to cis-gendered gay men, both the transgender and straight communities can benefit if at increased risk of contracting HIV.
PrEP requires assessment and baseline labs and then regular monitoring by a provider to ensure safety, proper use and allows us to screen and detect other STDs such as gonorrhea or chlamydia early and treat if needed. So how do you decide between oral and injectable PrEP? Let’s compare how each works, their pros and cons, and who might benefit most.
Oral PrEP: Familiar, Flexible, Accessible
Truvada
Available in generic form (tenofovir disoproxil fumarate + emtricitabine)This is the original PrEP pill: one tablet once daily. For anal sex, it reduces risk of HIV by up to 99% when taken consistently, and 96% or more during vaginal sex (where the drug concentrations are lower) even if condoms are not used. However doctors still strongly encourage condom use to prevent other STDs and pregnancy.. The FDA label and CDC guidance describe this dosing and monitoring. FDA Access Data+1 Common side effects / safety: Most people tolerate Truvada well. Common mild side effects include GI upset and headache. Important safety considerations: rare declines in kidney function and modest reductions in bone mineral density (usually reversible on stopping), so baseline and periodic kidney checks are recommended. The medication guide lists these risks. FDA Access Data+1
Descovy
Descovy is the alternative oral PrEP option. Essentially, it contains the same active ingredients as Truvada, but they are formulated differently and there are some important differences. Also taken once daily, it has the same effectiveness as Truvada in MSM (men who have sex with men) studies. However, according to FDA guidelines, Descovy is not as effective in preventing HIV transmission with vaginal sex as Truvada. Importantly, compared with Truvada, Descovy tends to have fewer side effects on the GI system and less impact on kidney function and bone density but can be associated with small increases in lipids and weight gain in some people. Descovy HCP
On-demand (2-1-1) dosing — what it is and who can use it
What is 2-1-1? The 2-1-1 “on-demand” schedule uses Truvada only: take 2 pills 2–24 hours before sex, then 1 pill 24 hours after the first dose, and 1 pill 24 hours later (so 2 → 1 → 1). If sex continues over multiple days, continue one pill daily until 48 hours after the last exposure. This method was studied in the IPERGAY study and is recommended for cisgender men and transgender women who have sex with men as a reasonable option when exposures are intermittent. It is not recommended for people having receptive vaginal sex, people who inject drugs, or populations where it hasn’t been studied. CDC+1
Efficacy: Studies and follow-up analyses showed very high protection from HIV (estimates in the mid-90% range among adherent users in those trials). PMC+1
Pros/cons: Pros — fewer pills overall for those with infrequent exposure, reduced cost and daily pill burden. Cons — requires planning, not suitable for everyone, and only Truvada (not Descovy) should be used in this way.
Injectable PrEP; more convenient, more effective.
Apretude
An intramuscular injection every 2 months after initial loading doses Apretude (Cabotegravir) is approved for all sexes and genders. It showed in MSM & transgender women 66% fewer infections vs daily oral PrEP (0.41% annual incidence vs 1.22%) and in cisgender women 89% fewer infections vs oral PrEP (0.21% vs 1.79%) This means it’s even more effective than oral PrEP and ideal for those who don’t like pills, prefer its convenience or have adherence issues. Side effects include injection-site reactions (most common), fever, headache. Rarely, allergic reactions. Other downsides include the cost and insurance coverage along with contracting HIV while on injectable PrEP can complicate the treatment options available.
Yeztugo
Yeztugo (Lenacapavir) became available in June 2025 and is a 6 monthly injection. The PURPOSE 1 trial found 0 HIV infections in the lenacapavir group vs 16 in Truvada → essentially 100% protection in trial participants. Side effects are low but include injection-site reactions, mild GI upset, headache with long-term data still emerging. Pros: Only twice-yearly injections; strong efficacy; could reduce adherence barriers even further. Being new, it is costly and insurance coverage is still emerging. There is less long-term safety data, but no worrying or concerning trends about its safety so far.
Which Option Is Right for You?
- Daily pill may be best if: You like flexibility, already take other daily medications, or cost is an issue.
- Injectable PrEP may be best if: You want long-term protection without daily reminders, have trouble with pill adherence, or value privacy.
Your healthcare provider can help weigh personal factors like other medications, medical history, and lifestyle.
Why Access to PrEP Matters
In Atlanta and across the South, HIV disproportionately affects LGBTQ+ and Black communities. Expanding access to PrEP HIV prevention—whether pills or injectables—saves lives and supports healthier communities. Yet research shows many patients still lack access to providers who are familiar with PrEP or comfortable prescribing it.
At Somerset Medical, we believe sexual health deserves the same respect and attention as any other part of healthcare. Whether you’re exploring PrEP for the first time or considering switching to injectables, our inclusive, judgment-free care makes the conversation safe and straightforward.
Bottom Line
PrEP is one of the most powerful tools we have to prevent HIV. The choice between daily pills and 6-month injectable PrEP depends on your lifestyle, preferences, and comfort. What matters most is finding an option that works for you—and having a doctor you trust to guide the decision.
Ready to learn more about PrEP options in Atlanta? Text or call (470) 666-5567 to learn more.