INSTIs: Top 10 reasons they Rock for HIV treatment

Today we have a guest post by the one and only, Dr. Darcey Wooten! (@Darcy_ID_doc) from @UCSD. Here we will cover why INSTIs rock for HIV treatment!

INSTIs are potent medications for the treatment of HIV. Most experts now recommend them as first-line for MOST treatment naïve patients. Here we will highlight how they came to be preferred.

https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/what-start-initial-combination-regimens-antiretroviral-naive?view=full

1) STARTMRK Trial

STARTMRK was one of the early studies showing RAL + FTC/TDF (pink) was better than EFV + FTC/TDF (green). RAL is extremely well-tolerated, but unfortunately doesn’t come co-formulated w/NRTIs.

https://journals.lww.com/jaids/FullText/2013/05010/Durable_Efficacy_and_Safety_of_Raltegravir_Versus.11.aspx

2) SINGLE Trial

And no surprise, dolutegravir (DTG) outperformed EFV as well! The SINGLE trial was a randomized double-blind, noninferiority study comparing DTG/3TC/ABC to EFV/FTC/TDF. In 833 patients, a DTG based regimen appeared superior with fewer adverse effects.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645960/

3) ACTG A5257

In ACTG A5257, rates of virologic suppression were similar between RAL, boosted darunavir (DRV/r) and boosted Atazanavir (ATV/r). However, RAL was more tolerable. PI group = ⬆️GI side effects. RAL also caused less elevation in lipids.

https://www.acpjournals.org/doi/10.7326/M14-1084

4) ARIA study

Further evidence for INSTIs came from the ARIA study, which enrolled women only. Patients were randomized to either DTG/3TC/ABC (Triumeq) or ATV/r + FTC/TDF. Though it was conducted as a non-inferiority study, outcomes clearly favored the DTG arm.

https://pubmed.ncbi.nlm.nih.gov/28729158/

5) FLAMINGO Trial

In the FLAMINGO trial, DTG looked better than DRV!!! This was a HUGE finding! To this point, nothing had ever looked better than DRV with respect to virologic suppression. We also see the very rapid rate of virologic suppression with DTG here.

https://pubmed.ncbi.nlm.nih.gov/26424673/

6) SPRING-2 Trial

But what about choosing between INSTIs? SPRING-2 was a randomized, double-blind non-inferiority study comparing DTG + 2 NRTIs vs bid RAL + 2 NRTIs. 411 pts were in each arm – 81% in the DTG group and 76% in the RAL group had viral suppression.

https://pubmed.ncbi.nlm.nih.gov/24074642/

7) GS-1489 and GS-1490

And we can’t forget about the championship final: BIC vs DTG. GS-1489 compared BIC/FTC/TAF to DTG/3TC/ABC and GS-1490 compared BIC/FTC/TAF to DTG + FTC/TAF. The INSTIs demonstrated impressive viral suppression and BIC was non-inferior to DTG.

https://pubmed.ncbi.nlm.nih.gov/28867497/

8 and 9) GEMINI 1 and GEMINI 2

And finally, the GEMINI 1 and 2 trials showed that DTG/3TC was non-inferior to DTG + FTC/TDF as 1st line therapy in pts with VL <500,000, no RAMs, and no HBV. Would also caution the use of this regimen if CD4 <200. Still, not too shabby!

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32462-0/fulltext

10) Weight Gain with INSTIs 🙁

But remember, INSTIs aren’t perfect—no medication is. We have recently recognized the role of DTG and BIC in weight gain and associated metabolic consequences. This study by @Paulsax nicely demonstrates this concept. This will need more exploration

https://academic.oup.com/cid/article/71/6/1379/5586728

So there you have it – 10 studies demonstrating the impressive effects of INSTIs on HIV!

Did we miss any go to studies? Thanks to @Darcy_ID_doc for putting this together!

Have something to add?

Originally tweeted by Infectious Diseases Fellows Network (@ID_fellows) on 14 April, 2021.

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