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

The important ARV guidelines session featured 4 speakers and a discussion/scenario panel

We STARTed (sorry) with the START study preliminary results by Jenny Hoy. Jenny discussed the data we've all been looking at since it was released in May. Essentially, we can now confidently recommend ARV for all people diagnosed with HIV, regardless of CD4. The study was ceased early due the strength of results in both AIDS and Non-AIDS complications in the immediate ARV arm. The benefits were maintained regardless of age, gender, race, world location and CD4 and VL at entry to study. Worldwide ARV recommendations have updated accordingly. 

Next speaker was Julian Elliott who reminded us of other studies (TEMPRANO & CASCADE) which have shown similar data in terms of treatment benefit at higher CD4s. Understandably, the number needed to treat is greater with high CD4 counts.

As chair of the ASHM HIV guidelines, Julian re-iterated that the decision to start ARV, while recommended in all HIV infected patients, should be a patient & clinician collaboration. 

Mark Boyd was then tasked with summarising why the integrase inhibitors (InSTIs) are now first-line drugs. Pivotal and open label studies over the last few years have left no doubt that raltegravir, and more recently dolutegravir, show non-inferior (and often superior) efficacy, with minimal side effect profiles and a fairly high barrier to resistance. The tolerability of the InSTIs really make them an appealing option for almost everyone.

James McMahon concluded the formal presentations running through the important changes based on the updated DHHS guidelines. In short, Efavirenz - gold standard for a decade - is on the out due to side effects (dreams, dizziness, rash). In actual fact, it's been on the out for a while and prescribers have been updating accordingly, however the official recommendations have now followed suit. James spoke about Darunavir, a PI worth considering, but not reimbursable on the PBS criteria as a first line agent. 

The scenario based panel followed with the abacavir CV risk a main topic for discussion. The jury is still out. Most of us are not keen to prescribe abacavir, and thus Triumeq, if the CV Framingham risk is a concern.

Thanks for a good session! 

Excellent plenary session lead by Ed Gane discussing an overview of the swift evolution of HCV over 25 years!

I've summarised the main points: 

- HCV first identified in 1989 as non A non B

Current epidemic

- 80-100 million (300,000 in Aust & NZ) and is overtaking HBV as liver mortality 

- infection leads to premature death - especially co-infected HIV/HCV

- the disease burden will continue to rise as infected (ageing) patients develop complications such as cirrhosis and liver cancer.

So, how do we eliminate HCV? 

Vaccination?

- genomic diversity (both virus & host)

- funding diminished now DAAs so potent 

- likely not to lead to eradicate HCV

Public Health interventions?

- eg harm reduction in PWID (syringe programs etc)

- can only do so much - decrease prevalence by 1/3 in countries which employ reduction methods ( and most countries don't)

DAA therapy?

- we need patients to be diagnosed prior to any dent being made in HCV prevalence

- currently Aust has reasonable diagnosis rates, but very poor treatment rates

- DAAs offering a new treatment paradigm for HCV by combining effective drugs with minimal SE and short durations

- e.g. Ledipasvir/Sofosbuvir (Gilead) - daily, oral, 12 week program, IFN & RBV free with excellent SVRs (97%) in GT1. Even in Pugh B/C patients, SVR nudging 90%. In the co-infected cohort the results are equally exciting

- Abbvie & Merck also have similar products 

We CAN eliminate HCV with:

- FUNDING

- better diagnosis rates 

- access to fibroscan 

- significant increased capacity to treat and uptake 

- employ treatment as prevention 

- make prescribing more accessible (in discussion in AUST) 

- FUNDING!!

Exciting to think that Australia looks to be leading the way!

Congratulations to Cuba! 

Certified as having eliminated HIV & Syphilis transmission from mother to child.

In 2007 the WHO developed the elimination of MTCT policy - all regions have been working towards elimination. There is a structured validation process to approve and celebrate successful countries/regions. Cuba is the first country to reach this target!

Worldwide there's much work to be done - almost 1,000,000 pregnant women have HIV. Assuming  a rate of 2% MTCT, there are a still a number of children diagnosed and a significant number more at risk. 

Great double session by John De Wit who discussed the current state of play with the VICPrEP study.

In summary - PrEP works! There have been a number of RCTs showing decreased HIV acquisition with PrEP. Of course, adherence is paramount to success.

One of the concerns put forward is that PrEP use may decrease condom use; risk compensation. 

VIC PrEP, thus far, has been a demonstration project. They have undertaken a multI-site , open label study. Participants have taken Truvada daily for 12 months.The 92 participants with follow up data took regular surveys to examine attitudes and behaviours regarding PrEP. 

They looked at the amount of regular & casual partners, frequency of sex as well as risk reduction methods - Serosorting, VL sorting, positioning, withdrawal and condom use. Interestingly , there was no change in sexual behaviour with regular partners while the main  significant change in behaviour with casual partners was some decrease in condom use. What does this mean? well, Yet to be determined as adherence to PrEP was generally very good.

However, it's  most important that PrEP is part of comprehensive package - with STI screening, condom use promotion. 

Look forward to further data from this study!