Hiv

[Olddaddy]

When I was in Thailand I started PRep medicine a few days before my travel 

In hindsight I should of taken it a week before 

In fact some days I missed my dose 

I started to get flu symptoms on my return to Australia 

It was a silly thing to do , thankfully I tested negative for my HIV test although my doctor said he will need to test again in 2 months 

As he said there is no assurance that Prep works 100% and you may want to consider your partner using a condom if they are in the high rusk category eg sex workers 

I have no idea of any of you are living with HIV and you may not want to disclose that .

Apparently you must take anti virals everyday , 

Unfortunately as I got older I became complacent ,

I won't take Prep everyday though unless I'm travelling 

I do wonder if many of you who have HIV are still ok in your lifestyle 

 

 

 

[PeterRS]

I had a Thai boyfriend who contracted AIDS and died in 1994. Although desperately sad, I was terrified about getting an HIV test even though I had always used condoms. AZT was on the market but very expensive. I just assumed I did not need it! Two years later I finally took a test and was negative. But the next year one of my closet friends in Hong Kong arrived at my apartment and told me he had tested positive. He was in a dreadful state. By then antiretrovirals had been developed and he was put on a course. Now nearly 30 years later and aged 70 he is still not only alive, he is enjoying life as much if not more than before. I believe he takes one pill a day (but not 100% sure it is only one).

[unicorn]

If you can't remember to take your pills every day, oral PrEP is not for you. There are injectable alternatives which can be dosed months apart.

[unicorn]

I should also add that if your "HIV test" was an antibody test only, then you very definitely need to be rechecked in 2 months, as one wouldn't expect a seroconversion so soon, and that test result could easily change. If the test also included an antigen test (i.e. viral RNA), then it's quite unlikely to be a false negative.

[unicorn]

I was at a medical conference today, and there is a new HIV prevention injection which lasts 6 months between injections. Unlike the previous injection, which is given in the muscle every 2 months, this one is injected under the skin. The big catch of this medication (Yeztugo/lenacapavir) seems to be that a majority (64%) of patients get a sizable lump under their skin, which averages 3 cm in diameter and lasted, on average, about a year! Although less common (31%), pain could last over 52 weeks! 

Half of the subjects received a placebo injection and were given Truvada or Descovy (FTC/TAF or FTC/TDF) pills, and half received the lenacapavir and dummy pills. 

The most frequent adverse reactions associated with LEN SUBQ injection use in PURPOSE 1 and PURPOSE 2 were ISRs. The most common ISRs (all Grades) in at least 2% of participants who received LEN in either PURPOSE 1 or PURPOSE 2 are presented in Table 1. Table 1. ISRs (All Grades) Reported in 2%a of Participants Receiving LEN in PURPOSE 1 or PURPOSE 2 Injection Site Reactions PURPOSE 1 PURPOSE 2 LEN (N=2140) FTC/TAF or FTC/TDFb (N=3205) LEN (N=2183) FTC/TDFb (N=1088) Nodule 64% 17% 63% 39% Pain 31% 24% 56% 53% Induration 4% <1% 16% 10% Swelling 4% 5% 7% 10% Pruritis 2% 1% 3% 3% Erythema 1% 1% 17% 19% Bruising <1% <1% 3% 4% Warmth <1% <1% 2% 2% a Frequencies are based on all injection site reactions attributed to study drug (or to the procedure) by the investigators.

Nodules

Injection site nodule was reported in 64% of participants who received LEN and resolved more slowly than other ISRs. The median duration of nodule associated with the first injections of LEN was 350 days (IQR: 182–470). The median of the maximum observed nodule diameter from each participant was 3 cm (IQR: 2–3.5). Qualitative descriptions of the visibility of injection site nodules were not routinely reported, but, where reported, the majority of injection site nodules were palpable but not visible.

Other ISRs

The other ISRs reported in more than 2% of participants who received LEN were pain (31%), swelling (4%), induration (4%), and pruritus (2%). The median duration of induration, of 8 which resolved more slowly than most ISRs, was 173 days (IQR: 22–267).

(ISR stands for injection site reactions)

[Riobard]

The ratios were actually 2:2:1 for PURPOSE 1 (LEN : F/TAF : F/TDF) the cis-gender women population sample study; and 2:1 for PURPOSE 2 (LEN : F/TDF) the men and gender diverse population sample study. The latter more relevant to most of us. 

What catches my eye most for PURPOSE 2 are the supplementary bacterial STI data, not packaged in the original NEJM paper eleven months ago, but soon afterwards shown in the manner appended below, depicting the consequences of not using condoms. Not that it isn’t consistent with what we already know about STI incidence in the context of HIV PrEP.

One way to interpret person-years is that if the LEN trend for the entire study sample were to be theoretically reflected in any one individual study subject, that person would acquire a combined total of gonorrhea or chlamydia infection on approximately 8 separate occasions going forward 10 years. Bear in mind that condom use is not restricted or tracked in the research, so the incidence rates are actually higher, to an unknown degree, among persons consistently not using condoms.

[unicorn]

I agree. It's silly to take these anti-HIV meds without also using condoms.

[Riobard]

Simply landing, by misfortune it seems, in the Lenacapavir research was unhealthy for the comparison group assigned to daily FTC/TDF and LEN placebo. The oral PrEP incidence rate was 10 times that of the well-known previous observational cohort study (ANRS PREVENIR), for similar population parameters, in which the incidence rate for either daily or on-demand Truvada trended at the same level as for the more recent Lenacapavir study injection recipients. Thus, having been, by happenstance, in the study evidently better for one’s HIV infection incidence outcome would yield similar efficacy as the relative efficacy purported by Lenacapavir compared to conventional oral PrEP … about 90%.

You don’t have to pre-establish an agenda of meta-analysis to objectively reference apparent contradictions in outcome. No academic attempt to responsibly synthesize PrEP would omit the outcome difference 

This is what happens when researchers are so biased and disingenuous that they are keen to introduce the background of their aims, yet in discussion stages omit reference to the enormous differential between the findings for the comparison group they wish to describe as deprived by virtue of not accessing the “favoured” (bias source) product and previous research findings that document what could realistically be expected when sticking to oral uptake.

Here we have a marketing thrust that asserts that a vastly more expensive PrEP option is substantially superior to a comparative generic oral product, the latter at pennies to the dollar, when it is merely noninferior at the level of breakthrough infection incidence by person-years denominator when you drill down into the reasonably manageable breadth of PrEP research. In fact, the HIV seroconversion rates are virtually identical … 0.11 cases per 100 person-years for LEN in PURPOSE 2; 1.1 cases per 1,000 person-years for oral PrEP in ANRS PREVENIR.

[unicorn]

If someone can be compliant, I'd go for orals. If there are side-effects, one can always stop. There are those, such as the OP, however, for which taking medication daily seems to be difficult. It's for those that injectables are a better choice. When taken as directed, most PrEP medications show efficacy closer to 97% than to 90%. 

[Riobard]

7 hours ago, unicorn said:

If someone can be compliant, I'd go for orals. If there are side-effects, one can always stop. There are those, such as the OP, however, for which taking medication daily seems to be difficult. It's for those that injectables are a better choice. When taken as directed, most PrEP medications show efficacy closer to 97% than to 90%. 

For sure, an injectable with effectiveness level such as Lenacapavir’s is a good bet, particularly if the proposed generic product drops to anticipated <$50 annually compared to Yeztugo’s current $28,000, but that is still a few years off and I believe the patent negotiation at this stage is that generic will be restricted to LMICs. Not sure where OP lives. 

I wasn’t putting forward 90% as any option’s efficacy compared to no PrEP. The way I set it up was the intention to indicate that depending on whichever Truvada-inclusive study’s cohort a research subject assigned to Truvada uptake found themself in could be at close to 10-fold greater risk for infection and that doesn’t add up. I should have emphasized It isn’t a true efficacy metric because it’s comparing the case incidence outcome in two studies. However, it’s no less valid to make such comparisons than to indicate efficacy relative to estimated background HIV case incidence in which PrEP or PEP uptake is baked in to an unknown degree.

Lenacapavir efficacy was described by the researchers as conferring 96% less infection risk relative to background HIV incidence. As you indicate, no PrEP taken as prescribed confers reduced risk as low as 90%. What I was pointing out was that the Lenacapavir researchers, based on comparing with the oral … Truvada … reported that Lenacapavir injection conferred 89% less infection risk. That leads the reader to believe that Lenacapavir is way more effective in a head-to-head comparison. However, when HIV case incidence for Truvada recipients in the Lenacapavir study, .92 cases per 100 person-years, is compared to the Truvada alone observational cohort study I referenced, 1.1 cases per 1,000 person-years, the degree to which Lenacapavir is purported as being more effective drops to 0%. 

An explanatory argument for such a difference (.92 vs .11), coincidentally the same reduced relative risk 89% in case incidence as was indicated comparing Lenacapavir to Truvada, could be that an experimental group was considerably less adherent to oral uptake than an observational group. But seriously, I would find it hard to buy that assumption even considering that a randomized trial is obviously a different methodological animal than a single product cohort. 

I grasp the difference between HIC and LIC privilege and resource access but If I or my public coffers or insurers had to fork out $28,000 for an equally clinically effective option … and given some amount of wiggle room for less than 100% oral meds taken as prescribed … because I suck at remembering daily pills I might try to find a way to overcome such adherence limitations. You can put a price on health even if a price shouldn’t be put on it. 

[Riobard]

On 10/17/2025 at 4:25 PM, Olddaddy said:

When I was in Thailand I started PRep medicine a few days before my travel 

In hindsight I should of taken it a week before 

In fact some days I missed my dose 

I started to get flu symptoms on my return to Australia 

It was a silly thing to do , thankfully I tested negative for my HIV test although my doctor said he will need to test again in 2 months.

Although you fell short of one-week lead-in dosing I’m not sure whether you meant you missed doses within the abbreviated lead-in or within the on-demand sequence. Maybe both? There may be a better episodic salvage option for an abbreviated lead-in with or without consistent dosing, that being immediately adopting 2-1-1. 

Interestingly, while one-week lead-in dosing or 2 start-up doses in on-demand 2-1-1-… structure is recommended for adequate protection, updated on-demand guidance states that the subsequent on-demand prophylaxis sequence is satisfactory at 1–1-1-… dosing if the latest dose was no more than 6 days previously, but 2-1-1 if a week or more. Now that’s much more flexible than how we perceived it years back when on-demand was approved, no?

This is not to say that one is restricted from 2-1-1-... in the subsequent sequence if the next occasion requiring protection is less than a week than the latest single dose. It’s your discretion and I certainly take 2 doses if merely a single non-dose day elapses from the previous sequence endpoint. If last dose in 2-1-1 is a Tuesday, my next 2-1-1 uptake the Thursday. Any toxicity concerns are assuaged by the rareness of such circumstances. If I needed to regularly double dose within short time frames I should be taking PrEP daily. 

However, my interpretation of how some interpret the guidelines is it is not recommended to compensate for a missed dose within the 7-day lead-in regimen by adding a second dose at any time, including 2-24 hours prior to activity as if you were initiating 2-1-1 given the notion of drug concentration absence or washout that renders you vulnerable. This seems rigid if strongly advised, and appears to be an artefact of the recommendation to not double-dose as compensation for a missed dose within a daily uptake regimen as long as uptake is generally very good at minimally 6 doses weekly. That said, it is deemed acceptable within a daily regimen plan to compensate for a missed dose within 12 hours past the typical uptake time, and the following dose as scheduled even though only an additional 12 hours or more elapses. 

There would be no reason to assume that failure to adhere to a full one-week lead-in would compromise the protection conferred by 2-1-1-… as called for when sexual activity imminently commences. The key is strict adherence once an on-demand sequence is initiated. 

The reason I put forward these ideas in detail is that you may have been unaware of your various prophylaxis salvage options in the context of missed doses that eventually created anxiety for you. In your shoes I’d have considered taking a lead-in category dose later than scheduled if I realized a dose was missed, or simply reverting to the established non-lead-in on-demand option depending on the details of less than optimal one-week lead-in uptake.