Most people on PrEP have no significant side effects. Some experience nausea, diarrhea, headache, fatigue, or stomach pain, usually in the first weeks, and these typically resolve. Truvada carries kidney and bone warnings that require routine monitoring. Apretude commonly causes injection-site reactions. No significant health effects have been seen in HIV-negative people taking PrEP for up to five years.
The common picture
HIV.gov states directly that PrEP is safe, and that no significant health effects have been seen in people who are HIV-negative and have taken PrEP for up to 5 years.[1]
The side effects that do occur are described the same way by both HIV.gov and CDC: some people taking PrEP may have nausea, diarrhea, headache, fatigue, and stomach pain, these side effects are usually not serious and go away over time, and you should tell your provider about any side effect that is severe, bothers you, or does not go away.[1][2]
The FDA label for Truvada gives the numbers from PrEP trials. Adverse reactions reported by more than 2% of Truvada participants and more frequently than by placebo participants were headache (7% versus 6%), abdominal pain (4% versus 2%), and weight decreased (3% versus 2%).[3] The gap between drug and placebo is narrow, which is a useful way to read a side-effect list.
Truvada: kidney and bone monitoring
This is the part worth taking seriously rather than being frightened by. The Truvada label lists serious potential side effects including new or worsening kidney problems, up to kidney failure, and bone problems — bone pain, or softening or thinning of bones, which may lead to fractures — along with worsening of hepatitis B, lactic acidosis, and severe liver problems.[3]
That is why monitoring exists. CDC states that before starting PrEP you must take an HIV test to make sure you don't have HIV, and that while taking PrEP you'll have to visit your health care provider routinely as recommended.[2] Those visits include kidney function testing.
Descovy (emtricitabine/tenofovir alafenamide) uses a different form of tenofovir and is one of the two daily oral options, though CDC notes it has not been studied for HIV prevention among people assigned female at birth who could get HIV through receptive vaginal sex.[4] If kidney or bone concerns are on the table, that is a specific conversation to have with your provider about which oral option fits.
Injectables: what the shots feel like
Injection-site reactions are the headline for Apretude and they are common. The FDA label reports that in HPTN 083, injection-site reactions occurred in 82% of participants receiving Apretude every two months, compared with 35% on daily Truvada; in HPTN 084 the figures were 38% versus 11%.[5]
Common does not mean intolerable. Of the 2,117 participants who received at least one Apretude injection in HPTN 083, 1,740 (82%) had at least one injection-site reaction — and only 3% of participants discontinued Apretude because of them.[5] Other reactions reported in at least 1% of participants included diarrhea, headache, fever, fatigue, sleep disorders, and nausea, generally at low single-digit rates.[5]
For lenacapavir, CDC specifies that injections go into the abdomen — at least 2 inches from the navel — or the anterior thigh, as two 1.5-mL injections at least 4 inches apart, with the upper arm under study as an additional site.[6]
Lenacapavir's safety record comes from two large Phase 3 trials: 2,134 participants received it in PURPOSE 1 and 2,179 in PURPOSE 2, and 99.9% or more of those participants remained HIV negative.[7] That is a substantial body of tolerability data for a twice-yearly injection.
A practical note: injection-site soreness or a small firm lump is expected and usually settles within days. Persistent, spreading, or worsening reactions are worth a call.
What to actually do about side effects
Give the first month a chance where it is safe to. Both CDC and HIV.gov describe early gastrointestinal side effects as typically resolving over time, and taking oral PrEP with food often helps.[2]
Do not simply stop. Stopping PrEP quietly leaves you without protection, and there are three other approved options plus generic alternatives to switch to.[1]
Do call about anything severe or persistent. HIV.gov's instruction is to tell your provider about any side effect that bothers you or does not go away.[1]
And keep your monitoring visits. They are how kidney and bone effects get caught early, when they are reversible.
Related questions
Will PrEP damage my kidneys?
It is a real but uncommon risk with tenofovir disoproxil fumarate, which is why the label carries a kidney warning and why routine monitoring is built into PrEP care. Most people's kidney function stays normal. If a change shows up on labs, your provider can switch you to another option before it becomes a problem.
How long do PrEP side effects last?
Usually a few days to a few weeks. Nausea, headache, fatigue, and stomach upset are most common when you first start and typically fade as your body adjusts. Taking the pill with food often helps. If something is still bothering you after a month, that is a reason to call rather than to quit.
Are the shots worse than the pills?
Different, not worse. Injection-site reactions are very common with Apretude, but only about 3% of trial participants stopped because of them, and there is no daily gastrointestinal adjustment period. Many people find two to six visits a year easier to sustain than 365 pills.
Does PrEP affect fertility, weight, or mood?
PrEP is not associated with infertility. Weight decreased was actually slightly more common than placebo in Truvada PrEP trials, at 3% versus 2%. Sleep disorders were reported in a small share of Apretude participants. If you notice a change you did not expect, mention it — most have another explanation worth checking.
Related from RiseUpToHIV
References & Sources
- HIV.gov — Pre-Exposure Prophylaxis (PrEP). States PrEP is safe with no significant health effects seen over up to 5 years, lists common side effects, and advises reporting persistent side effects; also lists the four approved options.. ↩ ↩ ↩ ↩
- CDC — Preventing HIV with PrEP. Lists diarrhea, nausea, headache, fatigue, and stomach pain as side effects that usually go away, and requires an HIV test before starting plus routine follow-up visits.. ↩ ↩ ↩
- FDA — TRUVADA prescribing information. Reports PrEP-trial adverse reactions (headache 7%, abdominal pain 4%, weight decreased 3%) and serious warnings including kidney problems, bone problems, hepatitis B worsening, lactic acidosis, and severe liver problems.. ↩ ↩
- CDC HIV Nexus — Clinical Guidance for PrEP. Documents F/TAF (Descovy) as a daily oral option excluding people likely to acquire HIV through receptive vaginal sex.. ↩
- FDA — APRETUDE (cabotegravir) prescribing information. Reports injection-site reactions in 82% (HPTN 083) and 38% (HPTN 084) of Apretude participants, 3% discontinuation due to ISRs, and other adverse reactions at 1% or more.. ↩ ↩ ↩
- CDC MMWR — Clinical Recommendation for the Use of Injectable Lenacapavir as HIV PrEP. Specifies lenacapavir injection sites in the abdomen and anterior thigh and the two-injection administration technique.. ↩
- Gilead Sciences — Yeztugo (lenacapavir) FDA approval announcement. Reports 2,134 participants receiving lenacapavir in PURPOSE 1 and 2,179 in PURPOSE 2, with 99.9% or more remaining HIV negative.. ↩
Community publications like POZ, Positively Aware, and TheBody inform framing and lived-experience context on RiseUpToHIV. Every clinical, epidemiological, or public-health claim above is anchored to a primary source.