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Lovely morning plenary by Paddy Mallon discussing ART toxicities.
With the lofty ambitions of 90-90-90 upon us, there will be increasing numbers of people starting ART at higher CD4 counts. Given that all the regimens we would be prescribing have excellent efficacy, toxicities & tolerability is now firmly back in the spotlight.
Interesting point comparing tolerability and toxicity; in general, tolerability (side effect profile) is easier to identify and often brought up by the patient themselves. Patients have been known to put up with mild/moderate side effects if they are satisfied with their regimen.
Toxicities are often silent which means as clinicians we need to have appropriate monitoring strategies if we are to stay ahead of the game.
Paddy briefly talked to the PIs and lipoatrophy (now essentially obsolete), as well as some PK data suggesting the PIs may not have the level of association with insulin resistance or CV risk once thought.
Efavirenz got a mention - it's definitely out of favour now, ostensibly due to its side effect profile (dreams, rash, dizziness), though some of the data for abnormal dream is fairly subjective.
The main toxicities Paddy focused on were the big 3 silent toxicities due to the NRTIs
1. CV risk due to abacavir:
- Paddy's opinion is that the the evidence is conclusive with a number of studies, including the recent US NA ACCORD (palella 2015) showing a hazard ratio of 1.95 for AMI.
2. bone and kidney health due to tenofovir
- bone health seems to be predominantly lost in the initial 48 weeks on ART, implying that it is the ART, rather than HIV alone, which leads to decreasing BMD and subsequent increased fracture risk. Cessation of TDF leads to increased BMD.
- renal function - consideration for TAF is important - the cost will need to be taken into account.
And into the future?
- cost is and will remain an issue
- should we drop the NRTI altogether?
- the silent toxicities will become less silent as our HIV population ages
Thanks for a great summary of the topic