4th International HIV/Viral Hepatitis Co- Infection Meeting

Transcription

1 INSTITUTIONAL STRAPLINE 4th International HIV/Viral Hepatitis Co- Infection Meeting The Rocky Road to Viral Hepatitis Elimination: Approaches for simplified HCV diagnostics and screening algorithms: thoughts about a public health approach for LMICs Niklas Luhmann Médecins du Monde France Saturday - Sunday, July 2017 Paris, France

2 Conflict of interest No conflict of interest to declare

3 Background» Advances in the past 3 years in the assessment of non-invasive liver fibrosis and the availability of safe, well tolerated, and highly curative HCV antiviral therapy have transformed HCV management and essentially eliminated two core obstacles along the care cascade (C. Cooper; Lancet Gastroenterol Hepatol 2017)» Optimizing and simplifying algorithms of diagnosis and management will be key to approach global HCV elimination and to foster a real public health approach to HCV HCV testing is the gateway to HCV prevention, treatment, care and other support services.

4

5 Background» In 2015, of the 71 million persons living with HCV infection globally, 20% (14 million) knew their diagnosis, globally (WHO, Global Hepatitis Report, 2017)» The Region of the Americas had the highest proportion of those diagnosed (36%), while the African Region had the lowest (6%) (WHO, Global Hepatitis Report, 2017)» Lesson from HIV: The importance and difficulty of the first 90 Recent estimates report that 70% of people with HIV know their HIV status (UNAIDS, 2017)

6

7 Georgia: national HCV elimination plan

8 Georgia HCV Elimination Strategy Goal Elimination of HCV by ensuring prevention, diagnostics and treatment of the disease Targets By % of people living with HCV are diagnosed 95% of those diagnosed are treated 95% of those treated are cured

9 HCV Elimination Strategy Strategy 1 Promote Advocacy, Awareness and Education, and Partnership for HCVassociated resource mobilization Strategy 2 Prevent HCV Transmission Strategy 3 Identify Persons Infected with HCV Strategy 4 Improve HCV Laboratory Diagnostics Strategy 5 Provide HCV Care and Treatment Strategy 6 Improve HCV Surveillance

10 National Population-based seroprevalence survey 2015 Conducted by NCDC and CDC, Atlanta Characteristic n % Estimated # nationwide 18 years Anti-HCV % 208,800 HCV RNA % 150,300 around adults living with HCV need to be identified

11 Scale-up of HCV Screening Programs» In an estimated patients have been screened» Identification of an estimated HCV antibody positive patients» assuming 75% viremia estimated patients identified (28% - assuming 100% retention between screening and viral load testing) *data are available through September 30, 2016

12 Scale-up of HCV Care and Treatment SOF introduced LDV/SOF introduced

13 Barriers and difficulties» With the excellent safety and tolerability and high cure rates of DAAs (>95%), the major remaining barrier to treatment is the under-diagnosis of HCV and limited access to treatment in the diagnosed population» Barriers to large-scale screening and diagnosis in the past can be explained, at least in part, by the complexity of diagnostic and monitoring algorithms the costs of the required tests the absence of reliable alternative tests to classical serological and molecular assays (such as point of care test) gaps in public health leadership and policy implementation insufficient funding for HCV testing infrastructure failure of health-care providers to consider diagnosis and offer testing patient reluctance to divulge risk factors patients not returning to the testing site to obtain results Another key obstacle is reliance on diagnostic tests that require venepuncture, preparation and transport of blood specimens, specialized laboratory expertise, and days, if not weeks, of processing time to yield results.

14 Complexity of diagnostics algorithm Background Recent guidelines for low- to middleincome countries suggest a public health approach as much as possible (WHO, Guidelines for HBV and HCV testing, 2016)

15 (Fourati et al. submitted to J Int AIDS Soc in June 2017)

16 (Azumi Ishizaki et al. Survey of programmatic experiences and challenges in delivery of hepatitis C and B testing in low- and middle- income countries; submitted for supplement issue in BMC Infectiuos Disease)

17 Testing and diagnosis: data from programs in 19 countries» 22 viral hepatitis testing programmes from 19 countries were interviewed» All but 4 of the programmes were based in LMICs» 45.5% were supported by non-governmental organizations or international organizations.» All but 2 programmes undertook targeted testing of specific affected populations» The majority of programmes were testing in hospital-based or other health facilities, particularly HIV clinics» Community-based testing was limited.» Nucleic acid testing (NAT) for confirmation of HCV and HBV viraemia was available in only 30% and 18% of programmes, respectively.» Around a third of programmes required some patient co-payment for testing. (Azumi Ishizaki et al. Survey of programmatic experiences and challenges in delivery of hepatitis C and B testing in low- and middle- income countries; submitted for supplement issue in BMC Infectiuos Disease)

18 In the serach of perfecto-check» Easy to use (decentralized settings, community settings)» Good performance characteristics» Universal: can be used in HIV/HCV, all genotypes etc.» Stable at high and low temperatures» Same test for diagnosis and verification of cure» Affordable

19 HCV NAAT for diagnosis NAAT techniques are mainly performed in centralized laboratories using rather expensive and complex technology Although the vast majority of low- and middle-income countries recommend routine viral load testing in line with WHO recommendations, implementation lags far behind as of 2013 only 23% of the need for routine viral load testing was met, with availability expected to increase to only 47% by 2019 (UNAIDS, 2016)

20 HCV NAAT point of care for diagnosis Point-of care : The Xpert HCV Viral Load test (Cepheid) is a WHO prequalified HCV NAAT test - designed to quantify HCV RNA in serum or plasma Xpert HCV Viral Load test for HCV RNA detection in capillary whole blood collected by finger-stick and plasma collected by venepuncture compared with the Abbott RealTime HCV Viral Load RNA assay in people attending drug health and homelessness services in Australia showed high sensitivity and specificity (Grebley et al. Lancet Gastroenterol Hepatol 2017) Although promising, it is still unclear whether a NAAT assay in a decentralized setting can achieve a price cheap enough to be used as a first-line assay. Another limitation is the rather low throughput volume of such solutions

21 Core AG for HCV diagnosis» HCV cag is detected early and during the natural course of HCV infection as a surrogate marker of viral replication» Nowadays, several assays are commercially available for specific detection of HCVcAg» The evaluation of these assays compared to HCV RNA was recently presented in a meta-analysis with Abbott HCV cag assay and the ORTHO ELISA-Ag test showing the highest sensitivity (up to 93.4% and 93.2% respectively), with very high specificity (>98%) (Freiman JM et al. Ann Intern Med 2016)» The Abbott HCVcAg quantification displayed high performances also in HIV and HBV co-infected patients from Cameroon (Duchesne L et al. J Int AIDS Soc 2017)

22 Core AG for HCV diagnosis» However, the use of HCV cag in LMICs still faces the problem of the availability of sophisticated laboratory equipment» Point-of-care HCVcAg are still under development» The main benefit of using HCVcAg over molecular methods is the cost of testing: cost for HCV cag tests was estimated from $10 50 in LMICs, lower than HCV RNA tests ($13 100).

23 Price of diagnostics

24 Costs of treatment, diagnosis and social support: PWID treatment program Kenya USD for ITEM PER PATIENT treatment period SOF/LDV 12 weeks/patient 1191 SOF/DCV 12 weeks/patient 2091 Routine HCV laboratory tests 537 Baseline Fibro scan 40 Social support 119 TOTAL (SOF/LDV) 1887 TOTAL (SOF/DCV) 2787 NAME OF TEST UNIT COST TOTAL COST (TREATMENT PERIOD) Confirmation PCR Viral load pretreatment and after treatment LFTs (done twice) Genotyping Fibroscan TOTAL 577 The Viral load is done in South Africa The test can be done locally trough long and they work with batches so need of a certain minimum number of samples for them to do the test

25 Skipping HCV genotyping?» Once diagnosis is confirmed, the current algorithm of HCV management requires HCV genotyping before therapy is initiated.» Very few examples from LMICs where genotype is skipped today» However, with the pangenotypic profile of next-generation DAAs (e.g. sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) pre-genotyping may no longer be required in the future» Whether genotyping can also be skipped when first-generation DAAs (e.g. sofosbuvir/daclatasvir or generics) will be used in LMICs is questionable (at least in cirrhotic patients)

26 Arabian Sea

27 Pakistan- General Demographic Features Population GNI per capita million 1400 USD Urbanization 37.9% People living in cities > 100,000 population 22% Karachi million Data source: 1. PDHS

28 Total Viremic HCV Infections Countries Responsible for 80% of Global Infections (Gower, E., et al. Journal of Hepatology 2014)

29 With courtesy of Prof. Saeed Hamid, Pakistan, 2017 Patients get both an ELISA/RDT for screening and a PCR for confirmation PCR is only qualitative In these outreach clinics we are encouraging general/family physicians to treat only the noncirrhotic simple cases as a start. Altogether approx 150 people have gone through the test-andtreat strategy so far. However there are a good number of drop-outs at the treatment initiation phase, most likely we think due to cost

30 AND DIAGNOSTICS