How antiretroviral drugs work:
the science behind PEP and PrEP.
PEP and PrEP both use the same class of drugs. Understanding why they work, and why timing and adherence matter so much, makes you a much better user of them.
Medically reviewed by Jude Ozioko, Pharmacist (PCN 024035) • Last reviewed October 2026
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When someone tells you that PEP must start within 72 hours, or that you need to take PrEP every day, or that lenacapavir only needs two injections a year, those statements make more sense once you understand what the drugs are actually doing at a cellular level. This is not a lecture. It is the background that makes every piece of HIV prevention advice click into place.
Here is the core idea: HIV needs to complete a specific sequence of steps to infect you permanently. Antiretroviral drugs block those steps. If the drugs are present before or during the critical steps, HIV cannot establish itself. Understanding which steps get blocked, and when, explains everything else.
The steps HIV must complete to infect you permanently.
HIV is not capable of self-replication. To make copies of itself, it must hijack a human immune cell, specifically a CD4 T-cell, and use that cell’s own machinery to reproduce. This process follows a fixed sequence of steps. Block the right step early enough, and HIV never becomes permanent.
Steps 3 and 4 are the critical intervention window. Reverse transcription must be completed before HIV’s DNA can be integrated. Integration makes the infection permanent. Block either step before it completes, and the infection never takes hold. This is the entire logic of PEP and PrEP.
Three classes of drugs used in PEP and PrEP, and what each one does.
NRTIs are the backbone of both oral PrEP and PEP. They work by mimicking the building blocks of DNA. When HIV’s reverse transcriptase enzyme tries to convert viral RNA into DNA, it accidentally incorporates an NRTI instead of the real building block. This terminates the DNA chain, reverse transcription cannot complete, HIV’s genetic material cannot be converted, and integration cannot happen.
Because NRTIs need to accumulate inside cells at protective concentrations before HIV arrives, daily dosing is essential for PrEP. The drugs are present and ready to intercept the reverse transcription step the moment HIV enters a cell.
If HIV’s RNA does somehow get converted to DNA despite NRTI activity, the next step is integration into the host cell’s nucleus. INSTIs block the enzyme integrase, which HIV needs to cut open the host DNA and insert itself. Without successful integration, HIV cannot become a permanent part of the cell and cannot replicate at scale.
INSTIs are included in PEP for this reason: if reverse transcription has already partially occurred before the drugs were started, a second line of blockade at integration gives PEP a second chance to prevent permanent infection.
Capsid inhibitors are an entirely new drug class with a completely different mechanism. Instead of targeting a single enzyme, they target the HIV capsid itself, the protein shell that surrounds and protects HIV’s genetic material. This shell plays a role at multiple stages: protecting the RNA during entry, docking at the cell nucleus, unpacking inside the cell, and assembling new viral particles. Lenacapavir disrupts the capsid at several of these points simultaneously.
Because capsid inhibitors work at multiple stages with high potency, and because lenacapavir’s formulation is engineered for sustained slow release, a single subcutaneous injection can maintain protective concentrations for approximately six months. This is why twice-yearly dosing is possible, something no single-mechanism drug could achieve.
The same drugs, two different strategies.
This is why timing is everything. The more replication cycles that complete before PEP is started, the more cells HIV infects before the drugs arrive. After 72 hours, enough cycles have typically completed that no amount of blocking new replication can prevent the infection that has already taken hold.
This is why daily adherence matters. If you miss doses, tissue drug concentrations drop. An exposure during a low-drug window means HIV encounters less resistance in the cells it targets.
How a twice-yearly injection achieves the same protection as a daily pill.
The challenge with oral PrEP has always been daily adherence. Miss doses regularly and protection weakens. The solution has been long-acting formulations: drugs that maintain protective concentrations for weeks or months from a single dose.
Lenacapavir works on a fundamentally different mechanism from oral PrEP. Rather than waiting inside cells to block reverse transcriptase, it targets the HIV capsid at multiple points in the lifecycle. Its high potency means a smaller total drug quantity is needed to maintain protection. Its formulation, a suspension injected just beneath the skin, forms a depot that slowly releases into the bloodstream over approximately six months.
The result is a drug level curve that starts high after injection and tapers gradually, staying within the protective range for the entire six-month period. There is no daily adherence calculation, no missed-dose window, no brief dip in tissue concentrations after a forgotten pill. Protection is simply continuous until the next injection date.
This is not a compromise on mechanism. The PURPOSE 1 trial found zero new HIV infections among 2,134 young women on lenacapavir. The protection is at least as robust as daily oral PrEP, and in real-world settings where daily adherence is inconsistent, substantially better.
Translating the mechanism into practical decisions.
Understanding how these drugs work changes the way you think about your own protection. A few things that make more sense now:
Starting PEP at hour 2 is meaningfully better than starting at hour 70. Not just somewhat better: HIV replicates exponentially. Each cycle doubles the number of infected cells. Intercepting at cycle 1 versus cycle 35 is a completely different clinical situation. If there was a real exposure, every hour of delay matters.
One missed PrEP dose is not catastrophic. The drugs accumulate in tissue over days. A single missed dose creates a small dip in concentrations, not an immediate gap. Two or three consecutive missed doses are more concerning because tissue levels fall significantly. Weekly or more frequent misses, however, progressively undermine the entire purpose of daily dosing.
Lenacapavir’s zero-miss profile is its single biggest advantage. For anyone whose life makes a consistent daily habit genuinely difficult, moving to twice-yearly injections removes the adherence equation entirely. The mechanism is more complex, but the user experience is dramatically simpler.
Ready to start? Our team will help you choose the formulation that fits your life and arrange everything on WhatsApp. Read the full guide to starting PrEP in Nigeria.
Questions about how HIV prevention drugs work.
QIf PrEP blocks HIV, why can’t it cure existing HIV infection?
PrEP prevents new infections by blocking reverse transcription and integration, the steps HIV needs to establish itself. But in someone who is already HIV-positive, HIV has already completed those steps, its DNA is already integrated into thousands or millions of cells in a permanent reservoir. PrEP’s drugs cannot reach inside those cells to remove the already-integrated viral DNA. That is why HIV cannot be cured with the current generation of antiretrovirals, and why PrEP must be started before infection, not after.
QDoes taking PrEP affect how well PEP would work if I needed it?
For oral PrEP: if you are on oral PrEP and have an exposure, you are already partially protected by the PrEP itself. If the exposure is high-risk and you are concerned, contact our team, the assessment of whether additional PEP is needed depends on your adherence history. For lenacapavir: lenacapavir belongs to a different drug class from the PEP regimen (TDF/FTC/DTG), so there is no overlap or interaction that reduces PEP’s effectiveness.
QCan HIV develop resistance to PrEP or PEP drugs?
Drug resistance is a real concern but primarily relevant in specific scenarios. For PrEP, resistance can develop if someone starts PrEP while unknowingly already HIV-positive, as the drugs then act as incomplete treatment. This is why a negative HIV test before starting PrEP is non-negotiable. Resistance to PEP is possible but rare, and typically occurs only when PEP is used in someone already infected with a resistant strain from their source partner. For lenacapavir, its multi-stage mechanism creates a higher barrier to resistance than single-target drugs.
QAre the drugs in PrEP and PEP safe for my kidneys and liver?
Tenofovir disoproxil fumarate (TDF), the standard oral PrEP backbone, is processed by the kidneys and can affect kidney function and bone mineral density with long-term use at higher doses. At the lower doses used in PrEP (versus full HIV treatment doses), these effects are generally mild and reversible. A kidney function test before starting and monitoring during use is standard. Tenofovir alafenamide (TAF) is a newer version with much better kidney and bone safety. Lenacapavir and the integrase inhibitors (dolutegravir) used in PEP have no significant kidney or liver concerns at standard doses.
Now you know how it works.
PrEP puts the drugs in your tissues before HIV arrives. PEP races to block HIV before it can establish itself. Both rely on the same fundamental principle: interrupt the replication cycle early enough, and HIV cannot take hold. Our team can help you choose the formulation that suits your life and arrange it on WhatsApp.
Start PrEP Today →Understanding the mechanism is the beginning. Using it is the protection.
Daily pill, twice-monthly injection, or twice-yearly injection. The biology works the same way. The choice is yours.
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