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

 

 

Hi everyone,

Another interesting and interactive panel discussion featuring Professor Jennifer Hoy, Dr Julian Elliot, Dr Mark Boyd, Dr James McMahon, and Dr Mark Bloch. This discussion built on earlier plenary session presentations on Theme B: ARV Guidelines - When and What to Start.

Three interactive clinical scenario on starting ART were presented to the audience and the panellists. These cases reflected the daily practical challenges facing clinicians and patients in deciding the best regimen to start that will optimize treatment outcomes with minimal side effects. Dr Mark Bloch pointed out that  the decision on what to start should be tailored to the patient, taking into consideration their presenting general health, medical history, concurrent medical conditions, life style, emotional and psychological wellbeing and  socioeconomic status.

It was interesting to note from the panellists that while for patient simplicity of the treatment regimen and toxicity are most important issues to consider in starting and continuing with medications, for clinicians the decisions on what to start can be very challenging. Clinicians always find themselves in situations where the existing guidelines do not provide them evidence based recommendations on what to start or when and how to switch from one regimen to another, or from one drug to another.

The question of Abacavir and the risk of AMI for patients with or without background risk of cardiovascular disease was highlighted as the perfect example where the current evidence is still contentious. Mark Boyd also highlighted another challenge facing clinicians when they have to manage patients who are generally not represented in clinical trials. He gave example of patients with reduced kidney functions (measured by eGFR) and the lack of evidence from randomized trials for the use of petentially nephrotoxic drugs like Tenofovir (TDF) or drugs which have been shown to impact creatinine clearance(Dolutegravir and Cobicistat).

The take home message from this session is that clinicians need to carefully engage and comprehensively review their patients before starting or switching ART. They need to make sure that their patients understand existing guideline recommendations and options available, the potential adverse events and toxicity for each drug(s) they are going to take. It is also important for HIV clinicians to work collaboratively with  non HIV clinicians, and allied health professionals in managing non-AIDS conditions. This will eventually optimize treatment outcome and minimize any drug–drug interactions and risk of non AIDS events.