ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

The pending introduction of a new formulation of tenofovir, a prodrug of the original formulation, raises the question of equivalence in terms of outcomes and virological suppression and adverse effects.  Don Smith and Mark Bloch presented data clearly showing that the newer formulation of tenofovir - tenofovir alafenamide (TAF) is superior to the original tenofovir disoproxil fumarate (TDF).  TDF, while a very effective agent, may cause clinical renal toxicity and adversely affect bone marrow density.  TAF is a novel prodrug that has a 90% reduction in serum plasma tenofovir levels and hence has the potential to reduce the adverse effects seen with TDF.

The speakers presented results of the GS-292-0109 study which looked at tenofovir disoproxil fumarate (TDF) 300mg switch to tenofovir alafenamide (TAF) 10mg in a cohort of well controlled patients at 48 weeks on once daily optimised background therapy.  1196 patients were randomised 2:1 to receive TAF based therapy to TDF based therapy with virological success occurring at least equally across both groups indicating non- inferiority.  Further positive results were seen in the TAF group where Statistically significant increases in BMD and multiple tests of renal function compared to those patients on theor prior TDF based regimen.  Lipid profiles however favoured TDF based regimens.  These results support the preferential use of TAF, especially in those at risk of metabolic and/or renal adverse effects.......well when it becomes available!

 

Tagged in: HIVAIDS2015

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.

The afternoon session: O21 - HIV and co-morbidity started with two speakers who complemented each others presentations very well.  

Dr Paddy Mallon provided an excellent overview of the cardiovascular risk factors associated not only with HIV itself, but the ART used in its management - especially abacavir.

Importantly he provided an overview on the potential role of increased platelet activity and their role in increasing the risk of vascular events and thrombosis. He concluded with reference to a current trial of pitavastatin to assess its potential in reducing hyperlypidaemic risk.  

Dr Janine Trevillyan followed on with an excellent overview of why HIV patients are at increased risk of CVD including dyslipidaemias, immune activation, platelet activity and other risk factors such as a higher incidence of smoking and diabetes.  

Janine then provided an overview of her current research activities on platelet derived soluble glycoprotein VI (sGPVI), where she described the observation that sGPVI levels are reduced in the month preceding a cardiac event in HIV positive patients and may have an important role in promoting cardiovascular disease in this population.  It was postulated that this reduction in levels may be linked to a pathological process leading to MI, or sign of an unstable plaque.

There seems to be a high risk of Cardiovascular Disease in HIV positive clients,even without cardiovascular risk factors.

Abacavir causes a platelet reactivity in HIV infected clients,this increases risk of thrombus,thus increasing risk of Myocardial Infarction.

Dyslipidaemia is now actually lower now than previously.Cholesterol levels now in clients with HIV now lower and better monitored than HIV negative clients.

Tagged in: HIVAIDS2015

Hello again.

As a follow up to this morning's plenary session, I attended this session which I believe will be of interest to some colleagues back in Australia. 

It was great to see Jenny Hoy from the Alfred Hospital moderating this session!!!!

The studies presented were

  • Statin Therapy Reduces Coronary Non-calcified Plaque Volume in HV Patients: A Randomised controlled Trial
  • Rosuvastatin Arrests Progression of Carotid Intima - Media Thickness in Treated HIV
  • Calcified Plaque Burden is Associated with Serum Gut Microbiota -Generated TMA in HIV
  • Varenicline vs Placebo for Smoking Cessation
  • Body Composition Changes after initiation of Raltegravir or Protease Inhibitors
  • Fracture Prediction with Modified FRAX in Older HIV+ and HIV- men
  • Exposure to ARVs and development of CKD (Chronic renal disease)
  • Renal and Bone Safety of TAF vs TDF

 

The studies were very well presented and indicate the importance of continued research into the co-morbidities that occur in our HIV positive patients

Just to summarise some of the conclusions from some the studies of interest

  1. Statin therapy prevented the progression of coronary athersclerosis and reduced overall plaque volume, especially lipid laden non calcified plaque volume .

Statin therapy reduced high risk morphology plaques

Statin therapy was safe and well-tolerated

Statin effects on arterial inflammation could not be adequately assessed but atorvastatin reduced a systemic marker of vascular inflammation

2. There appears to be a potential association of choline metabolism to subclinical atherosclerosis in HIV, assessed in relationship to plaque burden with the use of a sensitive CG angiographic technique

This relationship may be from altered gut flora or microbial translocation unique to HIV.

There is a need to assess the role of gut micro biome on CVD in HIV

3.The study on varenicline would be of interest to primary care physicians. Varenicline is safe and well-tolerated and effective as an adjunct to counselling in HIV positive patients as in general population and should be considered in HIV case management

Treatment of tobacco dependance in PLWH is a challenging priority.

4. PI/r or INSTI regimen initiation led to similar increases in limb fat with similar increases in central fat but ATV/r   containing arm tended to have higher gains in Lean Body Mass (LBM) than DRV/r but LBM gains were similar in pooled PIs vs INSTI

Higher pre-ART inflammatory markers were associated with increases in peripheral fat and LBM but not central fat

5. Studies have shown an association between the use of some ART and renal impairment as we all know. Implications from one of the studies in this oral presentation indicate cumulative increasing risk of Chronic Kidney Disease with increasing exposure to TDF, ATV/r, LPV/r in persons with an initially normal eGFR. The risk is cumulative over time.

A reminder that individual's risk of CKD can be calculated using the D:A:D CKD risk score to help determine benefits/risk  in incorporating ARVs into ongoing treatment regimen

and finally

6.  Looking at Tenofovir Alafenamide  (TAF)- the novel prodrug of Tenofovir (TDF) - we await in anticipation in Australia!!!! 

2 large RCT with detailed protocol specified renal and bone end points, confirmed favourable safety and tolerability profile of TAF  and that compared with TDF. TAF demonstrated no discontinuations due to renal Adverse effete, significantly smaller decreases in eGFR, significantly less proteinura, albuniuria and tubular proteinura, significanly less impact on spine and hip BMD and overall, greater increases in fasting lipids TC HDL same.

Most likely explanation for this = 90% lower tenofovir plasma exposure with TAF vs TDF

I would encourage colleagues to look up the webcasts which will be available later on.

Exciting work!!

Tagged in: croi2015

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