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.

HIV Co-infections, hepatitis B, hepatitis C and TB

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Comment: Abstract follows.

Modelling studies presented at CROI in 2016 predicted that prompt treatment of Hepatitis C with direct acting antivirals (DAAs) may substantially decrease the incidence of acute Hepatitis C in HIV + MSM. This study applies modelling to assess the impact of the rapid uptake of Hepatitis C DAA therapy on the incidence of acute Hepatitis C infection among HIV+MSM in the Netherlands.

In November 2014, all oral DAA therapy became available for F3-4 fibrosis and from September 2015 for F0-2 as well, resulting in rapid DAA uptake in Dutch HIV+MSM with chronic HCV. 65% were cured or on DAA therapy 6 months after unrestricted DAA availability (CROI 2017 Boerekamps et al). Also, in 2014 and again in 2016, individuals with acute Hepatitis C were offered immediate therapy in DAHHS study centres across the Netherlands.

 In 2014, 93 acute infections occurred in 8290 PYFU while in 2016, 49 acute cases were diagnosed in 8961 PYFU. The incidence in 2014 of 11.2/1000 showed a continuous decline to 6.9/1000 and 4.0/1000 within the first and second half of 2016. 1 year after unrestricted DAA availability in the Netherlands, the incidence of acute HCV in HIV+MSM decreased by 52%.

 A delegate enquired whether this reduction may be due to a change in sexual practices of the participants with increased condom use in the era of sexual transmission of Hepatitis C. Review of syphilis and gonorrhoea rates in study participants however, showed a rise in these STIs and would suggest otherwise. Further, next door neighbours Belgium are yet to gain unrestricted access to DAAs and their incidence of acute hepatitis C remains unchanged in recent years. Although the presenter indicated that this modelling study doesnt provide proof, it strongly suggests that for the first time, real-life data shows that HCV treatment as prevention averts new HCV infections in HIV+MSM.

Exciting to document what we think we know! This strengthens the argument to treat acute Hepatitis C in high risk MSM and injecting drug users. The last word went to an American delegate who posed the question to the Dutch presenter: Does this mean you should build a wall between the Netherlands and Belgium?

 

137LB SUBSTANTIAL DECLINE IN ACUTE HCV INFECTIONS AMONG DUTCH HIV+MSM AFTER DAA ROLL OUT

Anne Boerekamps et al

1Erasmus Univ Med Cntr, Rotterdam, Netherlands,

Background: The incidence of acute HCV (AHCV) among Dutch HIV+MSM has been high for >10yrs. Recent modelling studies predict that prompt treatment with direct acting antivirals (DAA) may decrease this incidence substantially (CROI2016 A536) but confirmation from real-life data is awaited. In 11/2014 all oral DAA therapy became available for F3-4 fibrosis and from 09/2015 for F0-2 as well, resulting in rapid DAA uptake in Dutch HIV+MSM with chronic HCV with already 65% cured or on DAA therapy 6 months after

unrestricted DAA availability (CROI 2017 Boerekamps et al). Also, in 2014 (in DAHHS1 study NCT01912495) as well as in 2016 (in ongoing DAHHS2 study NCT02600325) patients with AHCV were offered immediate therapy in DAHHS centers across the Netherlands. We hypothesized that this rapid treatment uptake will result in a lower incidence of AHCV among HIV+MSM.

Methods: AHCV was defined as HCV-RNA positivity, preceded by a negative HCV-RNA or HCV-IgG within 12 months. When stored plasma could not be retested, a normal ALT preceding the first positive HCV-RNA test together with a negative IgG any time in the past or a positive HCV-RNA and a simultaneous negative IgG was also considered diagnostic for AHCV. The incidence of AHCV was calculated by dividing the cases by the patient years of follow-up (PYFU). Data were available from 18 HIV treatment centers, geographically

spread across the Netherlands having +/-80% of Dutch HIV+MSM in care. We compared the incidence in 2014 (year preceding DAA availability) to 2016 incidence (first year after DAA availability).

Results: In 2014, 93 AHCV infections occurred in 8290 PYFU (=11.2/1000 PYFU, 95% CI 9.1-13.7). In 2016, 49 AHCV were diagnosed in 8961 PYFU (=5.5/1000 PYFU, 95% CI 4.17.2, p<0.001). The incidence in 2014 of 11.2/1000 showed a continuous decline to 6.9/1000 and 4.0/1000 within the first and second half of 2016. A relative increase in genotype 4 infections was observed from 19% (n=18) to 31% (n=15) (p=0.02). The absolute number of AHCV infections decreased both in patients with a first AHCV infection as well as in

patients that had an AHCV reinfection (=patients previously cured of an AHCV infection), while the proportion of reinfections remained constant: 21/93 in 2014 and 12/49 in 2016 (p=0.8).

 

Conclusion: 1 year after unrestricted DAA availability in the Netherlands, the incidence of acute HCV in HIV+MSM decreased by 52%. For the first time, real-life data show that HCV treatment as prevention averts new HCV infections in HIV+MSM.

Tagged in: CROI 2017
Tagged in: CROI 2017
Elimination of Hepatitis C and HIV coinfection in Australia

 As Australian clinicians, policy makers and communities affected by hepatitis C march into a new era of widespread, accessible Direct Acting Antivirals (DAAs), Dr Joseph Doyle from Melbourne’s Royal Alfred Hospital gave a timely presentation about the feasibility of eliminating HIV/Hepatitis C Virus co-infection.

The global burden of Hepatitis C Virus (HCV) infection is massive at 115-130 million people. Australia shares a relatively small burden of these infections, with an estimated 230 000 people living with HCV.  Globally, 2.2 million people are co-infected with both HCV and HIV. Between 7 and 10% of people living with HIV have HCV, with their odds of acquiring HCV six times that of the HIV-uninfected population.

As with HIV infection and the familiar 90-90-90 goal-posts, the WHO has set ambitious targets for viral hepatitis. By 2030, WHO aims to eliminate hepatitis C transmission, with 90% reductions in incidence, and 90% of those infected treated effectively. This is expected to prevent 7.1 million deaths between 2015 and 2030.

To achieve this, health policy makers must address specific gaps in:

-       Testing

-       Access to care

-       Treatment, and

-       Prevention

To be maximally effective, testing must be sufficiently frequent among populations at risk. Early diagnosis and treatment scale up to the point where 80% of all new cases of HCV were treated has been modelled to drastically reduce HCV incidence. Testing must be available at little or no cost to consumers, and provide reliable results. In Australia, antibody screening assays are widely available in organized laboratories with excellent quality assurance. Gaps persist in the diagnosis and assessment of hepatitis C: the current requirement for Nucleic Acid Amplification Testing (NAAT), genotyping, and assessment for fibrosis each presents a barrier to treatment. Multiple visits are often required to plan effective antiviral therapy, and each step represents a risk for disengagement. Algorithms for laboratories to deploy reflex HCV Ag/RNA testing in the event of reactive antibody screens would be useful. When these factors are combined models suggest improvements in treatment uptake and reductions in HCV incidence.

For hepatitis C and HIV coinfection, injecting drug use plays a role in up to half of cases. In contrast to HCV mono-infection, sexual transmission is also important, particularly among HIV+ men who have sex with men (MSM). Modelling suggests that sexual behavioural change could dramatically reduce sexual transmission of HCV, but the challenges to implementing this in an era of reducing condom use are considerable. Linking testing and early diagnosis with harm minimisation is important, and in some cohorts results in reduction of IDU risk behaviour.

Rates of testing for HCV are currently good among people living with HIV. Victorian data suggest that PLWHIV are tested an average of 1.4 times each year. Consideration should be given to increasing the frequency of testing, but restriction of this to higher risk individuals seems prudent.

Access to care has significantly improved in Australia in 2016. PBS-subsidised DAA therapy became available in March 2016, and unnecessary restrictions on prescribing for able prescribers were lifted in November of the same year. Australia wisely and bravely avoided the temptation to impose restrictions to access DAAs based on fibrosis, alcohol consumption and ongoing drug use. These aspects have seen the proliferation of interferon-free treatment in Australia. Interdisciplinary collaborations that have embraced participation by hepatologists, infectious disease physicians, sexual health physicians, public health professionals, virologists, general practitioners, and community members have liberated hepatitis C treatments from hospital environments to the community where much wider, more acceptable, sustainable implementation can develop. The multidisciplinary Consensus Statement on hepatitis C treatment has been instrumental in facilitating community provision of hepatitis C treatment.

Effective antiviral treatment of hepatitis C is the cornerstone of hepatitis C elimination. Although the safety and efficacy of the current generations of DAAs have provided extraordinary advances in the treatment of HCV infection, further advances are needed. The development of well-tolerated, safe, efficacious, pangenotypic regimens that require increasingly less reliance on fibrosis status and previous treatment history would be beneficial.

Communities at risk of coinfection include people who inject drugs and men who have sex with men predominantly, but those born overseas in countries with hig prevalence of both infections should not be neglected. 

Cost effectiveness of interferon-free DAAs is well-established for those with advanced liver disease, but the cost of treating those with early infection without fibrosis is well within Australia’s resources. 

Harm reduction strategies around injecting and sexual behaviour are an important part of primary prevention, but also crucial in preventing reinfection after successful therapy. Treatment offers opportunities to collaborate with harm reduction agencies, and reinforce messages of risk minimisation.

Although no highly efficacious vaccine for hepatitis C has been developed, the public health role of partially effective vaccines should be considered. The role for such vaccines will depend on the degree to which prevalence is reduced. If treatment uptake is high enough to reduce the prevalence of HCV to very low levels, a partially effective vaccine is unlikely to be of benefit. In the setting of ongoing high prevalence, or of high reinfection rated, a partially effective vaccine may be of considerable benefit.

Just as the HIV Cascade from the Kirby Institute’s Annual Surveillance Report informs HIV public health practice, so does the HCV care cascade. Priot to the introduction od DAAs in the community, only 2000 people accessed treatment for HCV. The introduction of HCV DAAs saw 27 000 HCV-infected people being treated by the end of July 2016, representing 13% of all people with HCV infection in Australia. We are on track to providing treatment to 40 000 people by the end of 2016. This enormous scale up of treatment for hepatitis C is unprecedented, and is a globally important public health intervention.

Networking models for HCV acquisition among PWID are well-described. Higher connectedness to communities with high HCV prevalence of confirms intuition. The high level of connectedness to others with HCV suggests strategies for increasing effective uptake among  networks. Similar strategies might be effective among sexual networks of MSM in whom HCV is prevalent. ‘Bringing your friends in’ is potentially effective for both PWID and MSM networks, suggesting a singular effective strategy for co-infected networks.

To meet the WHO targets regarding reduced transmission, modelling suggests Australia must treat 4 700 HCV-infected PWID annually. To meet WHO mortality targets, 5 600 HOV infected PWID must be treated annually according to modeling. Given the uptake of DAA treatment in its first year, Australia is on track for reducing both mortality and transmission targets. Costs for achieving this are estimated to be around $7 billion, but prudent deal-making on behalf of the federal government is likely to achieve thi results for substantially less cost.

Reducing HCV acquisition among PLWHIV requires an understanding of the complex environment in which HCV transmissions occur. Factors include rates of partner change, condom utilization, injecting behaviour, sexual dynamics that include group sex an use of sex toys, and concomitant partnerships. Agency-based modelling, which accounts for such complexity, suggests a greater efficacy in HCV incidence reduction than compartment based modelling, and supports the efficacy of providing treatment to those with high risk sexual or injecting networks.

How can this be implemented? The Co-EC Study examines the utility of nurse-facilitated hepatitis C treatment in community settings. This study demonstrated that most people aith coinfection can be treated safely and effectively in community settings, providing that collaborative care is available when needed.

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In summary, there are many parallels between HIV and Hepatitis C treatment. Treatment cascades are informative for both conditions, and there are many primary and secondary prevention messages that can be shared with benfit between sexual and injecting risk networks. Australia is on track to eliminate hepatitis C and HIV coinfection with its insightful, innovative adoption of community-based direct acting antiviral treatments for hepatitis C.

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

 

RT @hepqld: Curing #hepatitis C is easy, and no longer needs a specialist to prescribe treatment. Community doctors play a pivotal role in…

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