How to determine common LASTING side effects of medications (for HIV)?

May 10, 2017 12:46 PM

I want to compare different medications’ long-term tolerability. The Patient Information for each medication lists its side effects. But many side effects go away after a few days or a few weeks on the medication. I want to know what side effects commonly/very commonly persist after that adjustment period. The particular medications I want to know about are for HIV, and are listed inside.

The medications I want to know about are:
abacavir (600mg)
cobicistat (150mg)
dolutegravir (50mg)
efavirenz (600mg)
elvitegravir (150mg)
emtricitabine (200mg)
lamivudine (300mg)
rilpivirine (25mg)
tenofovir alafenamide (25mg)
tenofovir dispoxil fumarate (300mg)

I understand these are most commonly taken in combination pills, but I’m most interested to know the long-term tolerability of each component. I do know that side effects are termed “common” when 1-10% experience them, and “very common” when more than that do, but I think those rates include people who experience the side effect only during the adjustment to a new medication, which isn’t what I want to know. Any data, or resources for finding it, would be very helpful.

posted by daisyace to Health & Fitness (8 answers total)

data, or resources for finding it

Your doctor, your pharmacist.
posted by JimN2TAW at 12:56 PM on May 10, 2017

Response by poster: Your doctor, your pharmacist.

Thanks - this is for a work project, not my own health. I could ask a pharmacist, but I suspect that what they'll know comes from something published, and ultimately, I'll need something I can cite.
posted by daisyace at 12:58 PM on May 10, 2017 [1 favorite]

Do you have access to a medical library near you? Like one affiliated with a university or hospital connected to your work? This is a search a medical librarian could run for you.
posted by LKWorking at 1:09 PM on May 10, 2017 [1 favorite]

I think those rates include people who experience the side effect only during the adjustment to a new medication

I don't think this is the case - side effects, especially serious side effects, can be reported to the FDA (and similar bodies in other countries) at any time, and there are plenty of longer (like, multi-month or multi-year) studies of most of these drugs, since they're maintenance medications.

Where have you looked so far? PubMed is probably a good place to start, but this is a tricky question. (I'm a former school-of-pharmacy librarian and I'm not coming up with an obvious starting place for this, even if I still had access to all the resources I had when I worked in the library.) If someone has done a nice Cochrane review of the available data that would be handy, but I suspect that your best-case scenario is going to involve finding smaller individual studies and trying to compare the results, which is difficult even for experts.

Also a problem with longer-term drug studies is the fact that people for whom the side effects persist are less likely to stay on the drug. And side effects are arguably not taken as seriously as they should be by a lot of medical professionals.

Anyway, the usual medical terminology is not "side effect" but "adverse effect" or "adverse event," if that helps at all. A really good academic pharmacist (on the clinical side, not the pharmacology side) might be able to help you, or a medical/pharmacy librarian.

You're asking a tough question!
posted by mskyle at 1:29 PM on May 10, 2017 [1 favorite]

My suggestion would be to look for the package inserts, which should summarize the clinical trial results for each of the drugs. For example,
For tenofovir disoproxil fumarate (TDF): Viread.
For tenofovir alafenamide fumarate (TAF): Vemlidy.
Dolutegravir (DTG): Tivicay
Rilpivirine (RPV): Edurant

&c. If you want to find out more detailed information, the names of the clinical trials will be in the package insert. You can then google (or Google Scholar) the clinical trial results. These are usually published. Be aware that sometimes HIV drug names change as they go to market (for example GSK-744 vs Cabotegravir). For example, DTG's safety/efficacy trials were SPRING-1 and SPRING-2. SPRING-1 results:

At week 96, adverse events were reported by 92% of participants each who received DTG (all groups combined) and who received EFV (Table 2). There were no clinically significant dose-related trends in adverse events in participants who received DTG. Drug-related adverse events were reported for a smaller proportion of participants who received DTG compared with EFV (47 and 62%, respectively; Table 2). Nausea and headache occurred more frequently with DTG, whereas dizziness, rash, insomnia, and fatigue occurred more frequently with EFV.

I don't think it'll be easy to find any more detail than the published clinical trial results.
posted by Comrade_robot at 1:36 PM on May 10, 2017

This is a complicated project. There's is a ton of data out there on tolerability of the various antiretroviral medications for HIV, but it isn't all apples to apples. I suspect you aren't going to find a head-to-head comparison of all these medications, and keep in mind that the meaningfulness of comparing adverse event rates in one study for drug A to rates of adverse events in another study for drug B is unclear.

I don't know how familiar you are with clinical trial lingo. A key term to look for is "adverse event" (the term more commonly used, rather than side effect). Also, tolerability can often be gauged by the discontinuation rate; if many people are discontinuing (or, really, switching medications) due to adverse events, you can infer that tolerability is low. This measure is helpful because a side effect that was brief and minor will not show up in this measure. It doesn't, however, capture side effects that are annoying, but not so much as to justify a treatment adjustment. Here's a 96-week trial comparing raltegravir and doultegravir. You can see on page 929 that treatment discontinuation due to adverse events was very low for both arms: seven in the raltegravir arm and 8 in the raltegravir arm. This is likely what you are going to find for most of these medications. Modern antiretrovirals are generally highly tolerable.

Google Scholar and PubMed are the best search engines to use for this. Enlisting the help of a librarian is not a bad idea, if you have one knowledgeable on medical research.
posted by reren at 1:41 PM on May 10, 2017

You might also want to look at the Positively Aware HIV drug guide. In addition to the typical info, there's comments about each drug from a physician and an activist, which may give you some more in the real world information. The Positively Aware site might have additional articles that could be useful.
posted by conic at 3:34 PM on May 10, 2017

Response by poster: Thank you, everyone! A lot of these replies are helpful. At the least, they confirm as a group that the lasting adverse effects I'm looking for are, in fact, hard to tease out from overall adverse effects (including whichever ones dissipated in the first days or weeks of use). Good to know it's not just me failing to uncover a readily available answer -- and equally good to know where to dig for less readily-available ones. Thanks again!
posted by daisyace at 9:47 AM on May 11, 2017