Reverse Transcriptase Inhibitors

Science
#1

Going to try to keep this brief as possible and post some links to studies, along with plenty of speculation, regarding RTIs. As axolotl pointed out, the pertinent studies focus on cells where endogenous reverse transcriptase is highly expressed (cancerous and embryonic cells), and endogenous RTs shouldn’t be expressing at appreciable levels in healthy adult cells, meaning this RT inhibition is likely to be irrelevant to us. Also, 1 or 2 guys experiencing improvement during a certain treatment doesn’t mean much according to the history of the many other previous recovery/remission stories.

Still, the recent discussion around PFS and PrEP, Truvada, and Nevirapine is interesting for several reasons:

  • The study axolotl posted where restoration of normal growth and the re-expression of a few androgen-responsive genes was achieved upon DHT stimulation after hormone-resistant cells were treated with high concentrations of Nevirapine. An AR blocker prevented this effect of DHT on nevirapine-treated cells. This showed that nevirapine did restore the androgen signalling pathway’s sensitivity to stimulation by androgens.

  • I went looking for other stories of an effect of Truvada in “normal” people and potential unrecognized cases of “PFS” and found dozens of men and a few women reporting an unanticipated increase in sexual function, sometimes to the extreme, after starting PrEP medications. I could not find one person claiming a benefit from anti-retrovirals other than reverse-transcriptase inhibitors and cocktails containing an RTI. This was mainly limited to Atripla (Efavirenz, Emitricitabine, Tenofovir combo) and other drugs containing Efavirenz. There are a few others found via google search beside irishguy754 who had unexpected benefits from Truvada (Emitricitibine, Tenofovir combo) alone.

  • With the few exceptions taking Truvada, all of the people claiming increased libido and/or erections were taking PrEP or HIV treatment regimens containing Efavirenz (Atripla, Tribuss, and Sustiva), Etravirine (Intelence), or Rilpivirine (Edurant, Complera, Odefsey), which are non-nucleoside reverse transcitptase inhibitors (NNRTIs), like Nevirapine. A couple of the guys who switched from Efavirenz to Rilpivirine noticed that both had the effect of increased sexual function. One of them mentioned a greater effect of Rilpivirine compared to Efavirenz.

Woke Up With Major Hot Flash/Flush, Atripla? - Living with HIV/AIDS

Question for the men on Atripla… - Living with HIV/AIDS

Wow, Tripping on Atripla! :slight_smile: - Living with HIV/AIDS

Rilpivirine? - Living with HIV/AIDS

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(There are some anecdotes on sites other than POZ.com, but this appears to be the hub of discussion surrounding these types of meds)

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  • Efavirenz has been shown to be a very potent inhibitor of the human reverse transcriptase encoded by LINE-1 and was trialed as a chomotherapeutic in HRPC. It’s effect was seen as non-significant, but prevention of cancer progression appeared to correlate with concentrations of the drug and extreme variation in blood plasma concentration of the drug was observed among patients:

Despite the fact that primary objective of the trial was not met, it was striking to note a high variability in plasma concentrations of the drug that was actually comparable with previously reported concentrations in HIV patients ranging from 125 to 15,230 ng/ml

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  • LINE-1 knock-down using silencing RNAs (siRNA) had a similar effect on proliferation and differentiation of melanoma cells as the NNRTIs had on proliferation and differentiation of PC3 (an androgen insensitive lineage of prostate cancer cells). This doesn’t mean LINE-1 has any direct link with androgen signalling, but shows that its inhibition may normalize cells, leading to normal androgen signalling in the process.
    https://www.nature.com/articles/1208562

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  • Rilpivirine is considered more potent, longer-acting, and less harmful than other NNRTIs and a standard dose is 25mg/day. Doses of up to 150mg/day were “well-tolerated” in the clinical trials:
    https://academic.oup.com/jac/article/68/2/250/675261
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    My consideration is that the effect of Nevirapine on androgen signalling may be able to be achieved by higher doses of Efavirenz or Rilpivirine, while avoiding the severe toxicity of the required doses of Nevirapine.

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The Negatives:

  • These types of drugs (NtRTIs and NNRTIs) have been shown to inhibit human telomerase, with tenofovir having a particularly significant impact.

  • Tenofovir can cause kidney problems

  • Efavirenz can cause CNS effects, with many of the patients on the discussion boards mentioning extremely vivid dreams and a mental haze after waking.

  • Rilvirapine was associated with increasing risk of long-QT syndrome (rapid heartbeats) with increasing dosage.

  • There were 7-8 anecdotes of an RTI, or regimen containing an RTI, suspected of causing ED or lowered libido. Most were regimens containing protease inhibitors, but 2-3 anecdotes were truvada or atripla alone.

  • This is failrly speculative without studies directly addressing the effect that RTIs other than Nevirapine have on androgen signaling.

  • The benefits some of these people are noticing on RTIs may not have anything to do with androgen sensitivity.

I have an acquaintance taking Truvada as a prophylactic and he is having no noticeable side effects. Of course, results on a medication may vary, as we have all learned.

7 Likes
Prep medication, reversing pfs?
#2

Sooooo… you’re saying there’s a chance ? :wink: jk but thanks a lot for the research it’s appreciated, I will most likely try this sooner rather than later unfortunately I feel the benefit potential outweighs the risk

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#3

You’re welcome. There’s no subtext here. In all honesty, there have been so many treatments that looked promising at first, many with as much science to back them up as what was discussed here, which later turned out to be total duds or make some people worse-off.

#4

We’re 1 for 1 so far on this, the next guy to try it is going to but I feel like PSSD is different than accutane and fin which work very similarly

#5

Hey dubya one more thing, tons of “recoveries” and theories forsure but have any been said to do what that study said? To restore and resensitize cells to DHT?

#6

There was a hypothesis going around on one of these forums that HDAC6 inhibition by curcumin could alleviate AR hypersensitivity via decreasing AR nuclear localization.

I gave it a shot and felt curcumin worsened my sexual sensation and function while taking it. There was another story, I think of a PSSD patient who said they have been persistently worse-off after taking high dose curcumin supplements. His attempt was based on another PSSD patient saying curcumin had nearly cured him.

I also tried extract from danshen (red sage root) in 2015 and have only been worse-off since; although, I was going through a ton of intense stress at the time that may have also had something to do with the decline in sexual health. …Phytochemicals in danshen have been shown to decrease AR nuclear localization, reduce AR mRNA, and reduce AR protein levels though increased proteosomal degradation.

Granted, these are different mechanisms than what is described in the nevirapine study. Maybe they were both foolish ideas since an anti-androgen effect through AR inhibition was being sought after.

#7

just to mention that im starting prep tommorow but have to make notice that i dont respond to drugs, alcohol,benzos etc…
so if it doesn’t work for me doesn’t mean it wont work for u

i have pssd and not only physical sexual symptoms but also emotional bluntness etc…
so im not a marker for u
if i have improvements on prep than i can report back daily,if not im just gonna say that i don’t and thats it

best regards

3 Likes
#8

How you getting on? Have you tried it yet :thinking:

#9

yea
no effect good or negative so far
if i experience anything i will post here

3 Likes
#10

Thanks for the reply, hope you see some improvement :blush:

#11

Very interesting as always Dubya! Im in follow, i hope it can cure you. Im waiting for the improvements and news.

#12

hey man i just got a coquetel of dolutegravir tenofovir and lamivudine am i g2g??

its what they give people here as emergent PEP treatment

also in case it works is gene re-expression permanent you think??

#13

It did not work for zadig777 :choro:committed suicide

#14

should i be worried about DNMT1 overexpression ??

1 Like
#15

Nice. Vinny, you just provided a possible alternative mechanism of action, besides effects on reverse transcriptase, to explain why Tenofovir (ingredient of Truvada) might have had a positive influence on some of us.

Like you said though, increasing DNMT goes against what people conjecturing about epigenetic therapies are usually seeking.

Over 6 months since the first person described success with RTI/PrEP, and it appears to not be a useful treatment, going by the number of people who said they were trying it compared to the number of people who reported their experience with it.

#16

yeah, maybe if i can get nevirapine I’ll try one more month before i quit
also going by the homeostasis pov hydralazine could exacerbate that overexpression, being that it’s a direct hypomethylator, what do you think??

and thank you very much for the feedback, it means a lot when people help others doing things alone ;D

#17

I dunno. Nevirapine is harsh and if you look at the studies, you might be able to achieve the same effect with Efavirenz with much less risk.

I think it’s all a big risk without knowing more about this condition.

1 Like