Post-Exposure Prophylaxis (PEP) is an emergency medical intervention designed to prevent Human Immunodeficiency Virus (HIV) infection following a recent, potential exposure. PEP involves a 28-day course of antiretroviral medications, the same powerful drugs used to treat established HIV infection. When used correctly, PEP is highly effective, reducing the risk of acquiring HIV by over 80%. However, PEP is not an absolute guarantee. Failure, though rare, can occur when the biological or pharmacological balance of the treatment is disrupted.
Starting Treatment Too Late or Missing Doses
The success of PEP hinges on starting the medication as quickly as possible, ideally within a few hours of the exposure. HIV begins to replicate almost immediately after entering the body, establishing itself in local tissues before migrating to the lymph nodes. If treatment is delayed beyond 72 hours, the virus has likely established systemic infection and integrated its genetic material into the host’s immune cells. At this point, the antiretroviral drugs are less effective at clearing the infection, leading to PEP failure.
Once initiated, the complete course of medication must be taken every day for 28 consecutive days to maintain therapeutic drug levels in the bloodstream. Skipping doses or stopping the regimen early is one of the most common reasons PEP is unsuccessful. The goal of the 28-day treatment is to stop the virus from replicating until the body’s immune system can clear the residual HIV particles. Missing pills allows the virus to multiply without the full pressure of the drugs, providing an opportunity for the infection to take hold.
When the Virus is Resistant to Medication
PEP can fail if the individual was exposed to an HIV strain resistant to one or more medications in the prescribed regimen. Drug resistance occurs when the virus mutates, altering its structure so that antiretroviral drugs can no longer block replication. If the person who transmitted the virus had a history of inconsistent treatment, their viral strain may have developed resistance, which can be passed on during exposure.
To counteract this risk, PEP regimens use a combination of two or three different classes of antiretroviral drugs. This strategy, known as combination therapy, ensures that if the virus is resistant to one drug, the others remain active and suppress the infection. However, in rare instances, a highly resistant strain can evade the protective effects of the entire combination, leading to treatment failure. Healthcare providers often try to assess the source person’s treatment history, if possible, to select the most appropriate regimen.
Drug Interactions and Poor Absorption
The concentration of antiretroviral drugs in the bloodstream must remain above a specific therapeutic level to be effective. Certain other medications, including prescription drugs, over-the-counter remedies, and herbal supplements, can interfere with how the body metabolizes or absorbs the PEP drugs. This interference often involves the cytochrome P450 enzyme system in the liver, which is responsible for breaking down many compounds.
If a co-administered drug causes the PEP medication to be broken down too quickly, the drug concentration in the blood drops, rendering the treatment ineffective. Conversely, some interactions can increase drug levels, causing toxicity, which may lead the patient to stop the medication due to severe side effects. Additionally, physiological issues like severe vomiting or diarrhea can prevent the gastrointestinal tract from fully absorbing the PEP medication. Insufficient drug levels enter the bloodstream to combat the virus, resulting in treatment failure.
Subsequent Exposure to HIV
PEP is a post-exposure measure, meaning it only offers protection against the single event for which it was prescribed. It does not provide continuous or long-term immunity against future exposures. A person who engages in high-risk behavior while taking the 28-day course of PEP, or shortly after completing it, can become infected from a new exposure.
In such a scenario, the new infection is not a failure of the original PEP regimen, but the result of a subsequent, unprotected exposure to HIV. The infection is often mistakenly attributed to the original treatment failing because it occurs close in time to the PEP course. For individuals who anticipate ongoing risk, healthcare providers may recommend transitioning to Pre-Exposure Prophylaxis (PrEP), a daily medication taken to prevent HIV acquisition continuously.