Hep C infections drop by half after direct-acting antivirals are rolled-out

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A little more than a year after the Netherlands instituted a policy allowing unrestricted access to direct-acting antivirals (DAAs) for the treatment of hepatitis C, researchers have already seen a dramatic decline in acute hepatitis C virus (HCV) infections among one at-risk population, HIV-positive men who have sex with men.

These findings were reported at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) in Seattle, in a session that also included presentations on rising incidence of HCV infection among HIV-positive gay men in San Diego and predictions about eradication of HIV/HCV co-infection in France.

Direct-acting antivirals in the Netherlands
Anne Boerekamps of Erasmus University Medical Centre in Rotterdam and colleagues looked at outcomes among people with HIV/HCV co-infection after restrictions on the use of DAAs were lifted in the Netherlands. As of November 2015, DAAs can be prescribed to all people with co-infection regardless of liver fibrosis stage.

Abstract 1
Direct acting antiviral (DAA) therapy is a short, safe and effective treatment for chronic hepatitis C virus (HCV). Its high costs led to restricted reimbursement in most countries. Since 11/2015, DAAs can be prescribed to all HIV-HCV co-infected patients in the Netherlands, regardless of the fibrosis stage. We evaluated the impact of unrestricted DAA availability on HCV treatment uptake in HIV-HCV co-infected patients.
The ATHENA cohort collects nationwide data through an opt-out system from 98% of all HIV infected patients in care since 1998, and can provide an overview of HCV treatment uptake and impact over time in this population. Data were collected up until the database lock of 05/2016, i.e. 6 months after unrestricted DAA availability. Patients were included if they ever had 1 positive HCV RNA test, were classified as having a chronic or acute HCV infection, did not spontaneously clear HCV and were still in care (at least 1 clinical visit after 06/01/2015). The presence of severe chronic liver disease (clinical, radiographic or endoscopic signs of severe liver disease, whether or not combined with a histology or FibroScan® result), treatment characteristics and sustained virological response (SVR) were analyzed. When patients were treated more than once, only the most recent treatment and its outcome was included in the analysis.
Of the 22,042 HIV infected patients in the database, 1812 with HCV co-infection were included, of whom 1420 were still in care. Of the 392 patients not retained in care, 63 were lost to follow up, 269 had died and 60 had moved abroad. Of the 1420 still in care, 613 (43%) completed treatment with (PEG)-IFN +/- BOC/TVR, 413 (29%) completed treatment with DAAs, 94 (7%) had not yet completed DAA therapy and 300 (21%) remained untreated (figure). At the time of analysis, 65% (923/1420) of HCV-HIV co-infected patients had either been cured of HCV (n=829) or were completing DAA treatment (n=94). Notably, a high uptake was observed for patients without severe chronic liver disease: only 6 months after unlimited DAA availability, 33% (246/736) of those were cured with DAAs (n=192) or still on DAAs (n=54). The overall SVR after completing DAA treatment was 98% (404/413; 95%CI 96-99%).
Unlimited DAA availability resulted in a rapid treatment uptake among HIV-HCV co-infected patients without severe liver disease in only 6 months. Altogether, 65% of Dutch HIV-HCV co-infected patients are cured or expected to be cured in the near future.

Anne Boerekamps, Astrid Newsum, Colette Smit, Peter Reiss, Clemens Richter, Marc van der Valk, Joop Arends, Kees Brinkman, Bart Rijnders

Abstract 2
The incidence of acute HCV (AHCV) among Dutch HIV+MSM has been high for >10yrs. Recent modeling 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.
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).
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 4.1–7.2, p
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.

Anne Boerekamps, Guido van den Berk, Fanny Lauw, Eliane Leyten, Joop Arends, Marjo Kasteren, Mark Claassen, Charles Boucher, Bart Rijnders

HIV/HCV co-infection in France
Victor Virlogeux of INSERM in Lyon reported findings from a mathematical model looking at changes in the epidemiology of HIV/HCV co-infection in France in the DAA era.

Abstract 3
HCV Direct-Acting Antiviral (DAA) treatment uptake has drastically increased in HIV-HCV coinfected patients in France, resulting in HCV cure in more than half of patients at the end of 2015. We used model projections to estimate the impact of DAAs on HIV-HCV epidemiology over the next decade.
The model was based on epidemiological data from the French DatAIDS cohort. Eight risk groups were considered: high-risk (HR) and low-risk (LR) MSM and males/females heterosexuals, IVDU or patients with other risk. To model HIV-HCV epidemiology we used a mathematical compartmental deterministic model calibrated using the 2012-2015 observed incidence, prevalence and treatment coverage. Figures of the undiagnosed HIV-HCV epidemic were estimated from a previously published model (Supervie AIDS 2014). The impact of scaling-up DAA on HCV prevalence was investigated across the different risk groups.
On January 1st, 2016, 156,811 patients were estimated to be infected with HIV in France (under care: 131,861) of whom 7,939 (5.1%) had an active HCV infection with a detectable serum RNA (under care: 7,216 (5.5%)). Assuming a treatment coverage (TC) of 30%/year (observed rate in 2015), active HCV prevalence among patients under care dropped to 1.31% in 2021 and to 0.55% in 2026. Sub-analyses showed similar results in most risk groups, including LR MSM. Due to higher acute infection and reinfection rates, the predicted prevalence in HR MSM increased from 2.39% in 2016 to 2.46% in 2021 and 3.96% in 2026. Increasing TC in HR MSM to 50/70% per year decreased the prevalence in this group to 1.10/0.50% in 2021 and to 0.86/0.19% in 2026. With the current TC of 30%, the mean delay to reach
Our model suggests that DAA based treatments could nearly eradicate HIV-HCV coinfection in France within 10 years in most of the risk groups, including LR MSM. Consequently acute infections and reinfections in HR MSM and undiagnosed HIV-infected patients will account for the majority of infections in the future. Eradication in these 2 groups will require increased treatment coverage of acute infections in HR MSM and increased engagement in care for undiagnosed infections.

Victor Virlogeux, Laurent Cotte, Pascal Puglièse, Isabelle Poizot-Martin, Marc-Antoine Valantin, Lise Cuzin, Jacques Reynes, Eric Billaud, Thomas Huleux

HCV among MSM in San Diego
Turning to the US, Natasha Martin of the University of California – San Diego presented findings on the incidence of HCV infection among HIV-positive gay and bi men seen at the Owen Clinic, the largest HIV clinic in San Diego, between 2000 and 2015.

Abstract 4
International reports of a hepatitis C virus (HCV) epidemic among HIV-infected men who have sex with men (HIV+ MSM) associated with recreational drug use and with sex are causing concern. However, little is known about the HCV epidemic among MSM in San Diego. We assess HCV incidence among HIV+ MSM in San Diego in relation to injecting drug and methamphetamine use.
We performed a retrospective cohort analysis of HCV incidence among HIV+ MSM attending the largest HIV clinic in San Diego (UCSD Owen Clinic) from 2000-2015. Incident HCV infection was assessed among HIV+ MSM with a baseline negative anti-HCV test between 2000 and 2015, and defined as any new positive anti-HCV or HCV-RNA test after the start of follow-up. Group risks were defined as individuals who reported ever injecting drug use (IDU) or using methamphetamine.
A total of 2,396 MSM, who were initially HCV uninfected and had at least 1 further test during a median of 5.5 years of follow-up (IQR 2.8-9.2), were included in the incidence analysis. Overall, 149 HCV seroconversions occurred over 12,560 person-years of follow-up (incidence rate = 1.19/100py, [95%CI 1.01-1.39]), which increased over time (p=0.027, Fig.1A). Individuals were tested a median 3 times (interquartile range[IQR] 2-4) with a median testing interval of 1.2 years (IQR 0.6-2.2). Incident cases were identified on average of 10.6 years (IQR: 5.7-17.5) from HIV diagnosis and 3.6 years (IQR 1.5-6.4) from the first HCV negative test. Among individuals who seroconverted for HCV, 13.4% (20/149) denied IDU and methamphetamine use. HCV incidence was significantly higher among HIV+ MSM reporting IDU compared to those not reporting IDU (2.6/100py vs 0.97/100py, p
These findings suggest that HCV incidence is increasing among HIV+ MSM in San Diego. These rates are similar to London and other major European cities, and double that observed in the US Multicenter AIDS Cohort Study. This study also documented incident HCV infection among HIV+ MSM who do not inject drugs and an increased HCV incidence among individuals reporting meth use. Further work is needed to explain this trend and identify prevention strategies required to control the epidemic.

Antoine Chaillon, Christy M Anderson, Thomas C Martin, Edward R Cachay, David L Wyles, Davey M Smith, Susan J Little, Richard S Garfein, Natasha Martin

Abstract 5
Recognizing hepatitis C virus (HCV) as a major public health threat, the World Health Organization in 2016 released a strategy for global elimination by 2030 (i.e., 90% reduction in HCV transmission and 65% reduction in HCV-related mortality). The United States (US) National Academies of Sciences has deemed US elimination of HCV a feasible goal. HCV-Infected persons born during 1945-1965 are at greatest risk for HCV-related mortality. Certain strategies improve the HCV testing, care, and cure cascade and can reduce HCV-associated deaths. Provider education and adoption of clinical decision tools improve rates of HCV testing. Training and support of primary-care clinicians expand the workforce offering HCV services. Diagnosis of current HCV infection is improved by reflex testing of anti-HCV+ specimens for HCV RNA. Patient navigation services help persons begin and remain in care. At national and health-system levels, implementing policies and setting and measuring performance targets can improve quality of services. Issues with provider reimbursement for HCV treatment limit the number of persons treated through the Affordable Care Act and proposed changes might impact access to care. Creative solutions are needed for universal access to HCV treatment. Reducing US HCV transmission rate by 90% requires a targeted approach. Incidence is rising among persons who inject drugs (PWID); an increasing number of infants are born to HCV-infected mothers. Harm reduction services (e.g., clean injection equipment, drug treatment services) can prevent >70% of infections among PWID; HCV testing and treatment can enhance prevention. Access to these interventions is poor, particularly in areas with high HCV incidence. In the absence of an effective HCV vaccine, reaching elimination goals for transmission will require improved detection and investigation of transmission networks, increased availability of harm reduction services, affordable HCV therapies, and better evidence and capacity to deliver prevention services. Targeted intervention delivery to incarcerated and other vulnerable and marginalized populations is key to achieving elimination goals. With strong societal commitment and support for implementing comprehensive HCV prevention, testing, care, and treatment, HCV can be eliminated as a public health threat in the US.

John W Ward, Centres for Disease Control and Prevention

Aidsmap material
CROI 2017 abstract 1 (136)
CROI 2017 abstract 2 (137LB)
CROI 2017 abstract 3 (135)
CROI 2017 abstract 4 (134)
CROI 2017 abstract 5 (98)

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