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.

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I'll admit it now, I haven't been very up-to-date on the global approach to Hep C treatment, but this talk really brought me up to speed on several aspects.  Thanks to Dr Joseph Doyle for the great talk.

 

Global elimination targets

  • worldwide there are 2.2 million people living with HCV/HIV
    • compares to 37 million with HIV
    • odds of HCV infection were 6 times higher in people living with HIV
    • most HepC infections related to IVDU but some sexual exposure
  • target: 30% reduction in infections and 10% reduction in deaths (2020)

 

Elements needed for elimination

  • testing
    • early reliable diagnosis, frequent, regular testing
    • diagnosis allows connection with care and treatment, education, harm minimisation services, may influence at risk behaviour
    • Aust: recommends annual testing
      • but may need to recommend more frequent testing if we are serious about eradication
  • access to care
    • recent PBS listing to many new drugs
    • all are now interferon free
    • community prescribing is encouraged (after discussion with ID/hepatology)
    • no disease stage or drug/alcohol restrictions
      • in contrast to other countries where drugs are restricted to those with cirrhosis
      • this restriction would reduce costs but won't make much headway into eradication
  • effective treatment
    • sofosbuvir and velpatasvir (single pill regimen for all genotypes)
    • others are also coming soon
  • treating people at risk
    • target IVDU, MSM, born overseas in HPC
  • cost effective allocation
    • $20k for 4 years of extra life (if severe disease)
    • $60k for 6 years of extra life (if mild disease)
    • therefore even cost-effective to treat mild disease
      • many other options cost >$20k per year of life
  • harm reduction strategies
  • HCV vaccine

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The medications are effective, the funding is there to support the clinicians, patients are enthusiastic and actively seeking treatment - I think this is an exciting time for Hep C management and I am optimistic to see the future.

Andri Rauch, Bern University Hospital and University of Bern, Switzerland presented on the achievements and remaining challenges of Hepatitis C treatment.

We have all been fortunate to witness the breakthrough in HCV treatment from interferon-based regimens to DAAs:

  • Interferon acts by unspecific activation of innate and adaptive immune responses.
  • DAAs are specific and highly efficient in inhibition of the HCV life cycle.

The improvements in treatment efficacy in SVR genotype 1 infection:

  • by HIV status:
    • HCV SVR (cure) in both HIV/HCV co-infected, as well as HCV-monoinfected patients used to range from ~40% clearance in HIV/HCV co-infected patients to ~50% in HCV-monoinfected patients using PegIFN/RBV alone
    • Treatment with DAAs are now showing cure rates over 90% (and in some cases even up to 100%) in BOTH the co-infected and monoinfected patient
  • by cirrhosis status:
    • Cure rates of just over 30% have been observed in patients with cirrhosis who underwent treatment with PegIFN/RBV alone. The numbers were slightly better for patients with no cirrhosis at ~50% SVR on the PegIFN/RBV regimen
    • Treatment with DAAs are showing cure rates of ~95% and over.
  • by IL28B status:
    • SVR in IL28B risk allele were ~30% when PegIFN/RBV was used, compared to ~75% in IL28B protective allele carriers on the same regemine
    • Again, different DAA combinations show cure rates very close to 100%

Thus, DAAs achieve high cure rates irrespective of host and viral characteristics.

Changing from complex to simple treatments resulted a few (very welcomed) changes within the past 5 years:

  • Single tablet regimens
  • Treatment durations of 8; 12 or 24 weeks (depending on HCV genotype, cirrhosis status and past DAA failure)
  • No requirement for response-guided decisions
  • Minimal monitoring required

Andri discussed the remaining challenges:

  1. Difficult to treat: cirrhosis, NS5A RAS, GT3
    • lower SVR in GT3, cirrhotics and those with NS5A RAS
  2. Difficult to treat: renal impairment eGFR <30mL/min or haemodialysis
    • Suggested options for GT 1 and 4:
      • ombitasvir/paritaprevir/r +/- dasabuvir
      • grazoprevir/elbasvir
    • Other genotypes:
      • use sofosbuvir-based regimens with caution
      • close monitoring of renal function
  3. Drug-drug interactions:
  4. Events after SVR if therapy is started too late:
    • clinical improvement moderate in patients with decompensated cirrhosis with SVR
    • SVR does not eliminate risk of HCC
    • deferring treatment increases risk of liver-related events:
      • persistent metabolic risk factors
      • co-infections
      • liver toxicity due to drugs alcohol or co-medication
      • genetic predisposition to accelerated liver fibrosis
      • reversion of liver fibrosis/cirrhosis is frequent but not universal
  5. New epidemics and reinfections
  6. The cascade of care: comparing HCV with HIV (following the 90:90:90 targets). Increase of treatment rates to reduce prevalence by 90% in 2030.
  7. Affordability and reimbursement restrictions
    • Due to cost the DAAs are not readily available in many countries
    • The costs of treating all patients with hepatitis C would be equal to at least a tenth of the current annual cost for all medicines.
  8. Treatment-as-prevention and risk behaviour
    • Stabilisation in high-risk behaviour combined with an increase in treatment uptake is required to curb the HCV epidemic among HIV-infected MSM.
    • If this can be achieved, treatment-as-prevention can reach to HWO elimination targets (90% reduction in new cases by 2013)

In summary:

Goals of HCV therapy: achievements and challanges.

  • Cure HCV infection
  • Minimise adverse events
  • Provide universal access to therapy
  • Prevent HCV transmissions

 

"So, what are you doing about TB?"

There’s a particular gentleman at the AIDS 2016 Conference who causes a kerfuffle wherever he goes and I’ve witnessed his performance a number of times over the past few days.

At the end of every session he asks the lecturer “So, what are you doing about TB?”

It’s an AIDS Conference so most speakers are caught off guard when they don’t get a question about AIDS, but on Tuesday a speaker retorted “Well Anton, I didn’t know you were in the room, otherwise I wouldn’t have asked if there were any questions”.

I’m sure you’ll be pleased to hear that Dr Anton Pozniak finally got his own platform to speak in the plenary session.

He informed his captive audience that it’s all very good to treat HIV, but every year in Africa, Tuberculosis causes more deaths. He reminded us that our current TB vaccination is 95 years old and we need a new one.

Tuberculosis is diagnosed too late, with half the diagnoses made at post-mortem. HIV testing is improving, but we also need to be using a rapid test for TB. Whether it’s spitting in a pot or peeing in a jar, we already have the technology to test for Tuberculosis - but we need it to be quick, portable and affordable. 

We know Tuberculosis causes significant morbidity and mortality for people living with HIV (PLHIV). We also know that using Anti-Retroviral Therapy (ART) by itself is not sufficient to treat Tuberculosis. ALL patients co-infected with HIV & Tuberculosis need to be treated by a combination of ART and anti-TB medications.

We cannot shorten the duration of Tuberculosis treatment to any less than 6 months using our current anti-TB medications. New drugs are being trialled and some appear promising, but we’re even trialling old drugs to see if they might possibly work for Tuberculosis too.

Nelson Mandela once said “We can’t fight AIDS unless we do much more to fight TB”, but Anton isn’t keen to stop there. He not only wants to fight HIV and Tuberculosis, but he’s keen to eradicate viral hepatitis too.

Anton's dream is for everyone with viral hepatitis to be treated, but this dream comes with a price.

Hepatitis B treatment costs ~$15,000 in the USA, but the estimated true cost is $36. Hepatitis C treatment in the USA costs ~$84,000, but the estimated true cost is $62. Affordable medication can truly change the lives of millions of people around the world, but that's not yet happening.

Anton urged everyone to communicate and combine efforts to provide integrated health services for people in need. Testing and treatment should not only be for HIV, but also for Tuberculosis, Hepatitis B & Hepatitis C. 

We’re aiming to end HIV by 2030, but let’s aim to eliminate Hepatitis C and Tuberculosis too.

Anton closed his speech by saying that we need new 90:90:90 goals. We should aim for the cost of HIV treatment to be $90 per year, Hepatitis B treatment should be $90, and Hepatitis C cures should be $90 too.

NB - There was no kerfuffle at the end of his presentation as Dr Anton Pozniak wisely did not ask the audience if they had any questions. 

Day 2 of the conference was informative, fun and interactive. Opportunities to use smartphone technology to interact using live polls added to the experience. Here are my key GP take home messages from day 2.

1. Hepatitis C is curable and can be eradicated! At present only 1% of people with Hepatitis C are offered treatment. There is an urgent need for more community prescribers. The new DAA should be PBS listed by the end of this year. These drugs offer 8 week treatment times, are well tolerated, and have minimal drug interactions. Regimens will be interferon free. These drugs are highly effective (over 90-95% cure rates, even in advanced cirrhotics and HIV/Hep C coinfected populations).

GPs will play a major role in the eradication of Hep C. Treatment needs to be accessible and affordable globally.

2. Integrase inhibitors should now be first line agents of choice for ARV naive patients. They have outperformed EFV, DRV, ATV and just about everything else. They are well tolerated, suppress viral load rapidly, have few drug interactions and have a good metabolic profile. They are also increasingly available in 'one pill daily' regimens.

3. We need to include the transgender community in our sexual health campaigns and research (see my blog "PASH" 17/9/15)

4. We should be open to HIV self testing, in the US HIV self testing kits were well received by patients, and available by voucher, post, sex on premises venues, and even from vending machines in car parks! Patients who tested positive did link in with care, and these tests offered a convenient, out of hours testing opportunity, potentially reducing barriers to HIV testing.

Looking forward to day 3!

The Global Elimination of Hep C

Professor Edward Gane from Auckland NZ gave a visionary plenary presentation on how we may be able to eradicate hepatitis C.

Background on the Hepatitis C epidemic

Global infected population consists of 80-100 million people, with about 250,000 people in Australia

The global mortality attributable to liver disease has increased 60% since 1990, making it one of the fastest rising causes of mortality. Most of this can be explained from liver cancer and cirrhosis due to hepatitis C.

Can vaccination eradicate hepatitis C?

There are many barriers to the successful development of a HCV vaccine:

1. HCV factors:

  • HCV genomic diversity
  • T cell exhaustion
  • Impaired DC maturation
  • HCV NS3/5A inhibits IFN

2. Patient factors:

  • Host genomic diversity
  • Aging population
  • HIV co-infection

3. Other factors:

  • The chimp is the only animal model for vaccine development
  • Preclinical results do not translate to humans
  • With new highly effective treatment, there is reduced interest in vaccine development

Can public health interventions eraticate hepatitis C?

Harm reduction strategies (needle exchange, opioid substitution programs) are moderately effective, modelling has shown that these strategies will reduce HCV prevalence in PWID by a maximum of 30% over 10 years. This is insufficient to eradicate HCV. These strategies do have other benefits, such as reductions in HIV transmission, reductions in crime and increased engagement with healthcare providers. 

Can treatment eradicate hepatitis C?

 b2ap3_thumbnail_IMG_0703.JPG

This slide demonstrates the current hepatitis C treatment cascade on the left, where about 1% of people living with hepatitis C achieve cure/SVR. If we only improve treatment with newly developed drugs, then cure rate will increase to 1.8% (middle cascade). Significantly driving up cure rates to 80% requires that 90% of people living with hepatitis C need to be diagnosed, and 90% of those diagnosed need to take up treatment.

I would think that with access to well-tolerated and highly effective hepatitis C treatment, there will be an increased drive for clinicians to test at-risk patients for hepatitis C, and there will be increased uptake of hepatitis C treatment by those who have been infected.

In Australia we are on the cusp of possibly being able to achieve a ramp-up in hepatitis C management, as the Pharmaceutical Benefits Advisory Committee (PBAC) has recommended the listing of several new hepatitis C treatments (see slide below) AND have recommended that these be available for treating people at any stage of liver disease AND that these treatments can be prescribed by general practitioners in the community, thus allowing for a large-scale rollout of hepatitis C treatment, potentially setting the scene for eradication of hepatitis C.

b2ap3_thumbnail_IMG_0720.JPG