PrEP, HIV, Exposure, and What Happens Next … In 7 Questions, 5 Answers, 5 Pics … And More

(About the author…)

I recently saw a question posted online, or rather a series of questions, but it was predicated on the “what if, what then” of PrEP use and HIV exposure.

7 Questions

“How does Truvada work to protect us from getting infected with HIV? … Does that mean that if you get infected, the virus is always going to be there and Truvada will keep stopping the virus from replicating but doesn’t eliminate it? … What happens if, after 30 days, you stop taking Truvada? … Will the virus that’s already in your body start replicating? … Or what happens with it? … What happens with the virus if it enters your body while you’re on PrEP?…How is your body supposed to eliminate it? …”

So, here go replies in rapid-fire progression.

5 Answers, 5 Pics

1. How does Truvada work to protect us from getting infected with HIV?

Tenofovir/Emtricitabine (TDF/FTC, the two drugs usually in PrEP) are in a class of HIV antiretroviral drugs called Nucleotide Reverse Transcriptase Inhibitors (NRTIs). NRTIs are fake DNA building blocks that “jam” or stop HIV’s ability to copy itself into DNA inside immune cells. If HIV can’t get itself into the cell’s DNA, then it can’t take over the cell’s copying machinery, grow, overwhelm the immune system, and establish itself by lodging itself in organs and tissues.

NRTIs blocking HIV from getting into cellular DNA (AIDSIinfo)

2. Does that mean that if you get infected, the virus is always going to be there and Truvada will keep stopping the virus from replicating but doesn’t eliminate it?

PrEP is highly effective in all populations when taken properly, so the only ways it could fail are if a person were exposed to HIV before starting, if multiple pills are missed at the time of exposure, or if one is exposed to a strain of HIV resistant to the drugs. In such a rare and unfortunate case, yes, other than Timothy Ray Brown (the Berlin Patient) and the São Paulo Patient so far, if a person acquires HIV (whether during PrEP use or not during PrEP use), then it will always be there in the body. It hides in many organs and tissues all over the body, including the brain, lymph nodes, the gut, etc., so PrEP drugs will only stop the virus from replicating temporarily without eliminating it.

The two drugs in PrEP will also slow the process of HIV seroconversion, but they are not enough to fully treat and suppress an established HIV infection given how fast HIV can copy itself and grow in the body. While both drugs in PrEP are in the same class of HIV drugs, you need at least two different classes of HIV drugs (in two-drug and three-drug combinations) in order to treat and fully suppress an established HIV infection.

Where HIV hides (Avettand-Fenoel 2016)

3. So, what happens if, after 30 days, you stop taking Truvada?

When you stop taking PrEP, the protective drug levels fade in about 7-10 days.

TDF 30-day top-off and drop-off (Seifert 2015)

4. Will the virus that’s already in your body start replicating?

If you are taking PrEP properly, then it blocks HIV from copying and growing in the body. Next, the immune system identifies, neutralizes, breaks down, and disposes of the HIV that PrEP has blocked. (See questions 5 and 7 for more info/images.) That HIV can’t suddenly reverse the blocking process or otherwise start copying.

If, however, you were on PrEP and PrEP drops below protective drug levels (multiple and/or frequent missed pills, total PrEP stoppage) and the body is still being exposed to HIV more times (or if the body is exposed to a rare, mutated strain of HIV already resistant to the drugs even while you’re taking them), then the new exposures to HIV (or mutated HIV strains) can allow the cell-entering and HIV-copying process to start. If more HIV gets into the body after PrEP stops/drops, then it might be time immediately for PEP.

5. Or what happens with it?

Whenever HIV gets into the body, in hours and days, a race against time starts where the body tries to recognize and stop HIV before the virus lodges itself inside immune cell DNA and overwhelms immune system bases. With PrEP in the body before HIV, it gives the body time to recognize the invader by stopping the virus from getting into immune cell DNA. Over the course of those hours and days, the immune system recognizes any free-floating virus particles or cells with HIV inside, labels and immobilizes them, destroys them, and gets rid of the waste.

The immune system identifying, destroying, and getting rid of a virus (Lambert 2010)

6. What happens with the virus if it enters your body while you’re on PrEP?

This takes us back to questions 1, 4, and 5. If HIV enters the body and you’re already on PrEP, then PrEP “jams” HIV copying efforts inside the immune cells, the virus is essentially “frozen” or blocked from activity, and the body recognizes, breaks down, then gets rid of those free-floating virus particles and cells with frozen viral material inside.

7. How is your body supposed to eliminate it?

The immune system uses messengers (basophils, mast cells, dendritic cells), chemical labels and signals (B-cell antibodies and T-cell cytokines), destroyers (natural killer cells, neutrophils, eosinophils), and breakdown cells (macrophages, neutrophils) to identify free-floating HIV virus particles and any of its own cells with HIV inside, neutralize and destroy the bad genetic material and the contaminated cells, and then consume/break down/dispose of it all.

Basic components of the immune system (Yamauchi 2019)