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.

 

A few “Snapshots” from the Inflammation and Age-related Complications session, of interest:

 

1.       An update of D.A.D. data looking the association of cardiovascular disease and contemporarily used protease inhibitors, Atazanavir and Darunavir: Analysis looked at a prospective 7 years’ median follow-up (IQR 6.3 – 7.1) of 35,711 participants with 1,157 (3.2%) of participants having cardio and cerebro-vascular events (incidence rate 5.3/1000 PYFU (95% 5.0 5.6).  The analysis, with which we are now familiar, looked at crude incidence rates of CVD per 1000 PYFU stratified by cumulative use of ATV/r and DRV/r, and MI and Stroke separately. In this analysis, the cumulative use of DRV/r, but not ATV/r was independently associated with a small but increasing risk of 59% per 5 years’ exposure. The strength of the association is of a similar size for the older PIs but in contrast, does not appear to be modified by dyslipidemia.  We were reminded to exercise caution in interpretation as the study is observational only, and there are risks of unmeasured confounding. (L. Ryom et al CROI 2017 # 128LB.)

 

2.     Investigators in the North American AIDS Cohort Collaboration on Research and Drugs (NA ACCORD) looked at the incidence occurrence of Type 1 MI (atherothrombotic coronary event from plaque rupture) and the association with modifiable traditional risk factors by analysing the Population Attributable Factors (PAF) for MI.  They concluded that 43% of cases of MI in this cohort could have been avoided if these individuals did not have an elevated cholesterol, holding all other variables constant, 41% of MI were avoided by treating hypertension and 38% by smoking prevention. (K. Althoff et al CROI 2017 # 130.)

 

3.       A further analysis from the D.A.D cohort looked at cessation of cigarette smoking and the impact on cancer incidence. (N= 242 cases of lung cancer, and N=487 cases of smoking related cancers, excluding lung).  There were limitations in the study relating to the collection of cessation dates, intensity, duration or pack years unfortunately. However, the investigators concluded that smoking related cancers, excluding lung cancer, rapidly declined following cessation. Lung cancer incidence appeared to remain elevated in HIV patients several years after cessation, which is in contrast to studies in HIV negative individuals. (L. Shepherd et al CROI 2017 #131.)

 

Tagged in: CROI 2017

 

Venous thromboembolism (VTE ) risk is increased in HIV patients (5.7 -11.00/1000 person years) compared to the general population (1.0/1000 person years, with all data predating 2003. C. Rokx et al aimed to look at VTE in the current era in the Dutch Athena cohort with data between 2003-2014 on 14,386 patients.202/229 first VTE occurred in proximal leg veins or pulmonary arteries and 153/202 had withdrawn anticoagulants. 32 recurrent VTE occurred (59 VTE/1000person years; 95% CI; 41-83). Kaplan-Meier recurrence rates at 1, 2 and 5 years of follow-up were 16% 19% and 28% following unprovoked first VTE. When CD4 cell count is above 500, VTE incidence approaches that of the general population. Conclusion: Patients with persistent low CD4 cell counts might benefit from longer anticoagulant therapy. C Rokx et al, CROI 2017 Abstract #620.

 

I have seen a number of HIV patients with VTE over the years, the last being 2 months ago with the major concern at the time being a potential drug-drug interaction.  So, what new information was available at CROI regarding that drug-drug interaction?

 

As you are all aware, Ritonavir (RTV) and cobicistat (COBI) are antiretroviral pharmacokinetic (PK) enhancers that can inhibit several drug transporters, including P-glycoprotein (P-gp) and renal multidrug and toxin extrusion-1 (MATE-1). Dabigatran etexilate DE (trade name Predaxa) is the prodrug form of the oral direct thrombin inhibitor, dabigatran, and is a substrate for these transporters. Kristina M. Brooks and colleagues conducted a single centre open-label fixed sequence PK study on 16 healthy volunteers to evaluate the effects of separated and simultaneous administration of RTV and COBI on dabigatran PK. Findings: No significant changes in dabigatran exposure were observed with simultaneous RTV administration, possibly due to mixed induction and inhibition of P-gp by RTV. However, COBI resulted in significant increases in dabigatran exposure that persisted despite separating administration, most likely due to intestinal P-gp inhibition. These findings suggest RTV and DE can likely be co-administered, whereas the use of DE and COBI may require reduced dosing and careful clinical monitoring. K. Brooks et al CROI 2017 # 409. My patient is continuing to do well on Dibigatran (normal dose) and Genvoya. We will see Dabigatran used more often in HIV patients with thrombo-embolic disease.

 

 

 

 

 

Tagged in: CROI 2017

 

Day 3 CROI:

 

I am sure all the General Practitioners reading this topic are much more familiar with the management of patients with this condition than I am. 

 

Dr Rohit Loomba is a Gastroenterologist/Hepatologist at University of California, San Diego and he presented current work he, and colleagues, are undertaking in imaging and monitoring patients long term with NAFLD (Non- Alcoholic Fatty Liver Disease) and progression to NASH (Non-Alcoholic Steatohepatitis): Defined as >5% fatty infiltration on liver biopsy with pathognomonic ballooning of hepatocytes. NASH is now the second cause of liver transplantation in California.

 

NAFLD is divided into NAFL (non-progressive over many decades) and NASH (rapidly progressive over 7-8 years with a high mortality rate).

 

Some of the identifying clues to a patient with NAFLD are:  Metabolic Syndrome, Diabetes mellitus, older age, high AST/ALT, low platelets and low albumin. For these patients consider Hepatologist assessment for liver biopsy and appropriate imaging.

 

We are all aware that patients with HIV have increasing mortality due to liver disease. Dr Loomba indicated that NASH is 30-40% higher in patients with HIV infection and is independent of age, sex and BMI. He is currently looking at appropriate imaging strategies for NASH which monitor impact on pericardial fat and loss of muscle mass with progressive NASH. Sarcopenia is associated with increased mortality. His unit is also currently undertaking trials with a new medication Aramchol together with lifestyle intervention and weight loss strategies

 

TAKE HOME MESSAGE: We all need to be more proactive in assessing HIV infected patients with “fatty infiltration” of the liver on ultrasound especially if they have other associated clinical parameters.

 

Tagged in: CROI 2017

           Cerebral small-vessel disease (CSVD) is a common problem with increasing age and accounts for approximately 20% of strokes and 45% of dementia. In addition to age, hypertension is a major risk factor for the development of CSVD.  CSVD is characterised by white matter hyperintensities, silent infarcts and microbleeds.

           This cross sectional study examined the prevalence of CSVD in PLHIV (who immunovirologically controlled for at least 2 months on cART), comparing them with age and sex matched controls. A 3T MRI scanner was used and the diagnosis of CSVD was made by 2 neuro-radiologists who were blinded to serostatus.

           After adjusting for known risk factors, the prevalence of CSVD was twice higher in middle aged PLHIV (aOR 2.3).

           This study adds to the continually growing list of conditions that are more common in PLHIV, even where they are immunovirologically controlled. This therefore leads us to the question of how we go about managing or mitigating this effect. I did some further reading around up-to-date guidelines on CSVD. It seems that aside from managing blood pressure, there is little evidence to support the routine use of other agents, including statins or anti-platelets. These studies however have been done primarily in HIV negative individuals. The pathophysiological mechanisms underlying (at least some of) CSVD in PLHIV may be different. Given the extensive interest in the anti-inflammatory effects of statins in HIV, one wonders whether there may be a role in managing CSVD.

Tagged in: CROI 2017

Amber D'Souza outlined the epidemiology of anal cancer pointing out the significantly elevated risks for HIV positive MSM. She found DARE acceptable to patients within a study of 327 men.

Dr Jason Ong posed the question "What should we be doing with our patients now?"

He gave compelling reasons to screen for anal cancer targetting the most at risk, that is HIV positive men > age 50 ideally with an annual digital rectal exam to try and detect anal cancer at an earlier stage than is currently achieved with reactive checks related to symptoms.

50% of anal cancers are visible externally ie just looking would make a huge difference and currently less than 10% of HIV positive MSM have annual anal exams.80-100% will be found with DARE.

It is a simple safe cost effective and acceptable practice and can lead to better outcomes.

The evidence for screening for precursor lesions seems less compelling. 

HSIL is present in 30-50% of HIV positive gay men however only 1/400 progress to cancer in HIV positive men and 1/4000 progress to cancer in HIV negative men. 

SPANC has greatly increased understanding of this process.?Highest risk to progression to anal cancer is seen in those with persisting HPV16.

It was also suggested by Jason and Dr David Templeton to consider HPV vaccination in this group as despite the lack of evidence for efficacy, it may work.

From positivelife NSW we learned that most PLHIV  thought their risk for anal cancer was the same or lower than the general population.

84% of respondants in that survey and 64% HIV respondants had never talked to thier doctor about anal HPV/cancer- we should clearly be doing better than this.

Please join us for a memorial event celebrating the life of one of Australia’s leading HIV advocates, Levinia Crook… https://t.co/N7dof5xaGa

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