Apretude, the injectable form of HIV prevention (PrEP), reduced the risk of acquiring HIV by 66% compared to daily oral PrEP pills in its landmark clinical trial. That comparison is important to understand: Apretude wasn’t tested against a placebo but against an already highly effective medication. Its real-world advantage comes from eliminating the need to remember a daily pill, which is where many people’s HIV prevention falls short.
How the 66% Number Works
The main trial behind Apretude’s approval, called HPTN 083, enrolled cisgender men who have sex with men and transgender women. Participants were randomly assigned to either Apretude injections or daily oral PrEP. Those who received injections had a 66% lower chance of acquiring HIV than those taking the pill. Again, this doesn’t mean Apretude only blocks 66% of infections. It means it performed 66% better than a drug that itself prevents the vast majority of HIV cases when taken consistently.
The key factor driving that gap is adherence. Daily pills only work if you take them daily, and real-world adherence is often far lower than in clinical settings. Because Apretude requires an injection only once every two months after the initial doses, there’s no daily routine to maintain or forget. For people who struggle with pill fatigue, travel frequently, or simply prefer not to take a daily medication, that difference in convenience translates directly into better protection.
How Apretude Prevents HIV
The active drug in Apretude, cabotegravir, blocks an enzyme HIV needs to insert its genetic material into your cells. Without that step, the virus can’t hijack your immune cells to replicate. When injected as a long-acting suspension, the drug slowly releases from the muscle tissue into your bloodstream, maintaining protective levels for weeks at a time.
The Injection Schedule
Starting Apretude involves two loading doses one month apart, both given as injections in the gluteal muscle. After that, you continue with one injection every two months. You have a seven-day window on either side of each scheduled appointment, meaning you can be up to a week early or a week late without needing to change your plan.
If you expect to miss an appointment by more than seven days, the prescribing guidelines recommend switching to a daily oral version of cabotegravir for up to two months to bridge the gap until your next injection. If you miss the window entirely without bridging with oral pills, your provider will need to reassess whether restarting injections is appropriate, which involves getting retested for HIV before resuming.
The Long Pharmacokinetic Tail
One of Apretude’s most distinctive features is also one of its trickiest. After your final injection, cabotegravir doesn’t leave your body quickly. The drug remains detectable in the blood for many months. In the HPTN 077 trial, the median time for the drug to become undetectable was about 44 weeks for male participants and 67 weeks for female participants. Some individuals still had measurable levels more than two years after their last shot. People with higher body mass index tend to clear the drug more slowly.
This matters because as levels slowly decline, they pass through a range where the drug concentration is too low to fully prevent infection but high enough to create conditions for drug resistance. If you acquire HIV during this “tail” period, the virus may develop resistance to cabotegravir and potentially to other drugs in the same class, which are commonly used in HIV treatment. To manage this risk, guidelines recommend starting an alternative form of PrEP within two months of your final Apretude injection if you remain at risk for HIV.
Injection Site Reactions
The most common side effect is soreness where the shot is given. In the HPTN 083 trial, about 81% of participants reported at least one injection site reaction. That sounds high, but these reactions were typically mild: tenderness, pain, or a small lump at the injection site. Symptoms started within about a day and resolved in a median of three days. In the trial conducted in cisgender women (HPTN 084), the rate was considerably lower at 32%, though the reasons for that difference aren’t entirely clear. Most participants continued with the injections despite the temporary discomfort.
How Apretude Compares to Newer Options
Apretude was the first injectable PrEP option, but it’s no longer the only one. In 2025, the CDC issued a strong recommendation for lenacapavir, an injection given just once every six months under the skin rather than into muscle. For people who prefer even less frequent visits, that newer option may be appealing. Current guidelines encourage clinicians to discuss all available PrEP options, including daily pills, bimonthly injections, and twice-yearly injections, so the choice can match each person’s preferences and lifestyle.
Cost Considerations
Apretude carries a list price of roughly $3,700 per injection. With six doses per year (accounting for the loading phase in the first year), that works out to approximately $22,200 annually for the drug alone, before adding in the cost of clinic visits and lab work. Most people with insurance or access to assistance programs pay significantly less. Federal programs like “Ready, Set, PrEP” and manufacturer copay assistance can reduce out-of-pocket costs to zero for eligible individuals, but navigating coverage remains a real barrier for many.
For people at ongoing risk of HIV who find daily pills difficult to maintain, Apretude offers a genuinely effective alternative. Its protection is strong, its dosing schedule is manageable, and its main tradeoff, the long drug tail after stopping, is something that can be planned around with proper follow-up.