Q and A

Question

Are drug levels in penile tissue important for PrEP?

I read about PrEP levels having to be at good levels in vaginal and rectal tissue but can’t find any references to drug levels in the penis.

If a man is only the active partner will event-based dosing be okay?

Answer

Hi

Thanks for your question.

Event based dosing is fine for men whether or not they are top or bottom because it will achieve good drug levels thoughout the body. For men the important sites are in lymph tissue in the anus and groin.

For a man whose risk is only insertive – whether with a man or woman – any risk is likely to relate to how long infectious fluids are in contact with penile tissue. This includes the foreskin and glans – which are not skin but mucous membrane that are easier for HIV to get through. (This pic shows different tissue types and HIV risk)

PrEP doesn’t need to be at high levels in penile tissue because it is in the local lymph nodes – ie in the groin – where HIV develops. So even though the infection happens through the foreskin or glans, it takes hold in the lymph nodes and this is the tissue which need good drug levels.

The way drugs are process by the body is quite complicated though and varies for different drugs (and different people).

Tenofovir is interesting for reaching very high level in rectal tissue – about 10 x higher than in vaginal tissue and 100 times higher than in blood. This is why event-based dosing is good enough for receptive anal sex but not receptive vaginal sex. These internal tissues are also much closer to and include lymph nodes which is where HIV infection get hold and multiplies.

The evidence to support this answer comes from the lack of HIV transmission in PrEP studies where men have clearly been both active and partners.

4 comments

  1. Roy Trevelion

    Hi Hyun,

    Heterosexual men having vaginal sex can use on-demand dosing as well as daily dosing. Both of these can be started with a double dose. The double dose should be taken ideally between 2 and 24 hours before you first have sex on PrEP.

    For daily dosing, just carry on taking a single pill every day. But never take more than one double dose when you start PrEP

    Please see this guide to PrEP for more info on how to do on-demand dosing.

  2. Hyun

    Hello, I’m a heterosexual male.
    How long days should i wait to intercourse after Starting Prep????

  3. Simon Collins

    Hi Marco, thanks for your comments.

    Your first comment seems to miss that the penile tissue that lets infection occur is not skin but a mucous membrame. This is what the answer explains. HIV does not pass through skin. It can pass through some mucous membranes – and this explains why men catch HIV from insertive sex, whether circumcised or not. Circumcision reduces risk because the inner foreskin is not skin but a mucous membrane).

    Your second comment is also not quite right. HIV doesn’t persist in the mucosa – it travels through it. The exact time and way that HIV infection takes hold are still not well known – and scientists also have different views. They also have different views about where PrEP drugs are active and the target concentrations that are needed.

    Luckily, PrEP is so effective that so long as you taken is as prescribed (either daily or on demand depending on your circumstances) it is 100% effective, so long as the HIV is not drug resistant. This means that even if drug levels in the urethra (for example) are needed, PrEP must be reaches these tissues too.

  4. Marco

    I this is really inaccurate information.

    When you write “This includes the foreskin and glans – which are not skin but mucous membrane that are easier for HIV to get through” I would say the virus can also penetrate through the skin, and that is one of the reasons why uncircumcised men are more prone to catch HIV from being tops.

    When you write: “PrEP doesn’t need to be at high levels in penile tissue because it is in the local lymph nodes – ie in the groin – where HIV develops. So even though the infection happens through the foreskin or glans, it takes hold in the lymph nodes and this is the tissue which need good drug levels.”

    My comment to this is:
    How can you possibly share this information. As long as the viral infection persists in the mucosa, it is more likely that it will spread to lymph nodes and other tissues. Therefore concentrations of PrEP in these regions (specially in the urethra) are critical.

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