TRANSLATING SCIENCE TO END HIV IN EASTERN EUROPE AND CENTRAL ASIA

AIDS 2018 POST-CONFERENCE SYMPOSIUM

Georgia, 20 June 2019

www.iasociety.org Panel discussion: HIV, Tuberculosis and Hepatitis - The path forward for prevention and treatment: which way forward for an integrated approach?

Progress towards eliminating hepatitis C in : overcoming challenges through decentralization of services

George Kamkamidze, MD, PhD, MS Head of Research Department, Health Research Union (HRU), , Georgia www.hru.ge

www.iasociety.org HCV Treatment Sites within Elimination Program, January 31, 2019 (Total=40)

Total of 40 treatment sites: • 32 specialty clinics • 8 primary care centers

3 sites

Zugdidi 1 site Gori 1 site Akhaltsikhe Tbilisi 1 site 3 sites 1 site

155 physicians (ID specialists, gastroenterologist, primary care specialists ) Treatment Protocols

April 2015 – March 2016 Sofosbuvir (SOF) IFN-containing and IFN-free SOF regimens recommended based on various clinical scenarios (genotype, cirrhosis, previous treatment experience)

Since March 2016 Ledipasvir/Sofosbuvir (LDV/SOF) LDV/SOF is recommended in all genotypes Evidence supporting this recommendation included: - High prevalence of 2k/1b recombinant in Georgia - Results of some trials and observational studies indicating that LDV/SOF could be more effective that SOF alone

Since December 2018 Velpatasvir/Sofosbuvir (VEL/SOF) RBV-containing and RBV-free regimens recommended based on cirrhosis and previous treatment experience Georgia Hepatitis C Elimination Program Care Cascade, April 28, 2015 – January 31, 2019

Positive Anti- HCV Test (Total)* 108.747 73.4% HCV Confirmatory Testing 79.819 85.2% HCV Confirmed Chronic Infection 68.010 80.7% Completed Work-up (Enrolled) 54.858 99.6% Case Reviewed by Committee 54.649 99.9% Authorized to Begin Treatment 54.589 97.8% Initiated HCV Treatment 53.393 93.4% Completed Treatment 49.853 94.6% Eligible for SVR 47.162 75.1% Tested for SVR 35.427 98.2% Cured 34.805 Patients initiating treatment, Georgia HCV elimination program, April 2015 – January 2019

5000 60000

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Patients Initiating Treatment Cumulative Initiated Treatment PWID and HCV infection

 PWID are a major source of the burden of HCV in the country as documented by the national HCV sero-survey conducted in 2015

 Recent modeling indicates that priority treatment of PWID is needed to reach the elimination goals Milestones of HCV treatment integration initiative with HR services

April, 2016 • Meeting on integration of HCV treatment with harm reduction services – during EASL meeting, Barcelona

June, 2016 • Meeting of ECHO and CDC team with civil society representatives and NCDC at HRU/NEOLAB to discuss HCV treatment integration with HR services

• TAG recommendations

December 2017 • First meeting on HCV treatment decentralization

March 2018 • The session on integrating HCV treatment with HR services at the 5th National Hepatitis C Elimination Workshop HCV treatment decentralization

MOH Decentralization working group

Harm Reduction Primary Health Care group group Concerns related to integrating HCV treatment with HR services

• Unwillingness of HR center personnel

• Low trust among patients and preference to be treated at specialized clinics

• Quality of treatment and poorer outcome Study to evaluate barriers of integrated care

Funded by CDC/TEPHINET

• KAP survey of OST/NSP personnel on HCV care integration to evaluate readiness of health personnel to provide HCV care at OST/NSP sites.

• Qualitative evaluation of HCV treatment integration to understand barriers and challenges of HCV integrated care

• Patient satisfaction survey

• Chart review form for patients enrolled in integrated care services 13

Patient satisfaction survey

Question Answer % Is the location of medical facility convenient for you? Yes 93.3

How satisfactory are the conditions (building, waiting Good 97.9 space, sanitary conditions) at the medical facility?

Are you satisfied with the attitude towards you from your Yes 98 doctor? Are you satisfied with the attitude towards you from the Yes 98 nurses? 14 Patient satisfaction survey

Have you received comprehensive information about hepatitis C Yes 98% treatment and side effects?

Do you think that your confidentiality is protected during HCV treatment? Yes 96.2%

Do you think that it’s convenient to receive HCV treatment and Yes 98% methadone substitution therapy at the same clinic?

In general, how would you assess HCV treatment services at this facility? Very Good 93.5%

Will you recommend your family member/relative/friend (if interested) Yes 100% to be enrolled in National HCV Elimination Program? 15 Provider attitude to HCV treatment integrated services (IS)

(N=81)

Question Answer % Do you believe HCV treatment should be Yes 98 integrated with HR services

Do you believe your institution has enough Yes 82.8 administrative resources for IS?

Do you believe your institution has appropriate Yes 68.8 infrastructure for IS?

Willing to have IS at their institution Yes 98 Simplified Algorithm of pre-treatment diagnostics Simplified Treatment Monitoring Algorithm Pilot project

Integration of HCV treatment with harm reduction services

Funded by CDC Goal and Objectives

The goal of this project is to integrate HCV treatment with harm reduction services at four OST/NSP sites in different regions of Georgia Objective 1 To provide three NSP sites with security equipment to meet the MOH requirements to the facility for enrollment in HCV treatment Objective 2 To train personnel of NSP/OST sites enrolled in HCV treatment Objective 3 To introduce simplified testing algorithm among patients treated at harm reduction sites Objective 4 To monitor diagnostic and treatment process and to establish ECHO teleconsultations with the Hub Activities

Facilitate enrollment in treatment program for 4 sites with different services:

3 sites (in Tbilisi, and Batumi) having on-site RNA testing (FIND study site, arm 1)

One private OST site (using suboxone) with low linkage to HCV care rate Simplified regulation

• This project needed regulatory changes from MOH to make possible treatment integration at HR centers • The basic security measures (camera, security system, lockers) on site • Physician on site (contracted) • Simplified diagnostic and monitoring algorithm • Contract with elimination program provider clinic 22 Outcomes of pilot project

• Overall referral rate of patients from HR center to specialized clinics – 24%

• Integration of hepatitis C care with HR services is likely feasible and it is highly acceptable for personnel providing HR services.

• Based on experience of pilot sites, 4 new HR sites are selected for enrollment into HCV integrated treatment Challenges during the implementation of pilot project

• The treatment integration process took longer than previously expected and planned.

• The MOH regulatory agency requested multiple re-arrangements at HR sites to meet regulations for treatment integration.

• Because these sites were not operating as medical facilities before HCV treatment was introduced, starting treatment process was challenging and several steps of adjustments were needed to meet all requirements.

• Cases of personnel replacement and retraining needed

• Lessons learned during this process will be very important for further enrollment of the new HR sites in HCV treatment program. Hepatitis C treatment outcome among people with history of drug use

• Initial concerns among medical personnel and policy makers that PWID would have poor treatment compliance that would lead to poorer outcomes.

• Study estimating RVR and SVR rates among patients reporting injecting drugs compared to those without a history of injection drug use (data from clinic Neolab) Comparison of the two study groups

• Of the 4091 patients in the HCV elimination program by the time of analysis, 1775 (43.4%) had history of injecting drugs.

• The two study groups were comparable in age and fibrosis stage.

• Among PWID only 0.7% were females compared to 27.1% of females among non-PWID (p<0.0001).

• Genotype 3 predominated among PWID (43.2%) vs. non-PWID (34.8%, p<0.001).

• RVR was higher in PWID (97.3%) vs non-PWID (95.0%, p<0.01).

• SVR rates were comparable (96.0% vs 95.0%, p=0.24) Comparison of two study groups

Conclusion

Treatment outcomes among PWID were similar to patients without history of drug use, suggesting that treatment adherence may be sufficiently similar to achieve reasonably comparable clinical outcomes. Barriers and Facilitators to Enrollment in HCV Treatment Program among PWIDs

FUNDED BY MDM AND CDC

27 www.iasociety.org Methods

“Linked to care” individual was defined as: – Having positive anti-HCV screening and RNA/Core antigen test in elimination database “Lost to follow-up” was defined as: – Not having HCV RNA or Core antigen test in the elimination database at 90th day from being screened anti-HCV positive

Stratified sample of PWID having positive HCV antibody test between August 1, 2017 and January 31, 2018 and tested for HCV RNA/cAg Sample Size

• The stratification was done by Georgian Harm Reduction Network (GHRN)

• Proportional to size samples for lost to follow up and linked to care PWID were selected from each HR site

• 13 HR centers located in 10 cities were participating in the study

• Overall sample size = 500 PWID Study sites 31 Not having enough information about HCV program

P<0.05 0,1 0,09 0,08 0,07 0,06 0,05 0,04 0,03 0,02 0,01 0 Linked to care Lost to follow up 32 Age by linkage to care

P<0.05

<35 <35

Linked to care Lost to follow up 33 Do not trust/partly trust HCV elimination program

P>0.05

Linked to care Lost to follow up 34 HCV elimination program is not affordable

P<0.0001

Linked to care Lost to follow up 35 How to improve enrolment in HCV elimination program?

More information Must be Free Increase N of clinics

Linked to care Lost to follow up 36 Conclusions

Barriers to linkage to care among anti-HCV positive PWID include:

• Perceived high cost of care • Lack of information on elimination program • Perceived lack of access to treatment sites • Younger age.

Educational programs in HR sites to address misconceptions about the program may improve linkage to care among PWID. Pilot project Integrating HCV screening and simplified treatment services in primary healthcare

This model will provide the basis for the decentralization of treatment and care in PHCs and hospitals nationwide Decentralization of HCV diagnostics, treatment and care services in Primary healthcare centers (PHCs) in Georgia

Senaki

Poti Khashuri

Kobuleti Tbilisi Telavi Akhaltsikhe Akhalkalaki

Integration of HCV diagnostics, treatment and care services in at least one PHC of each district of Georgia

HCV diagnostics, treatment and care services should be integrated in 69 PHCs across the country during the first phase of the program Challenges/Gaps

 Declined enrollment in treatment program  lack of access to treatment program (financial barriers)  Current HCV screening & linkage modality not adequately effective

 Missing SVR Data (21%) Challenges/Gaps (cont.)

 Unnecessary barriers (centralized approval for treatment, camera recording etc.) preventing same-site testing and treatment

 Limited access to pan-genotypic DAAs preventing to eliminate genotype testing, to simplify the workup and reduce costs

 Limited treatment options for end-stage kidney disease patients including hemodialysis

 Scarcity of treatment centers (including PHCs, HR sites, TB clinics etc.) in some geographic and especially in rural areas Integration of HCV RNA testing on existing GeneXperts in Georgia to assist in current HCV care decentralization efforts

• In line with the existing decentralization projects FIND plans to support MoH and NCDC by providing cartridges and trainings to facilitate HCV RNA confirmation.

• This will support the decentralization of HCV care efforts in other settings, which could be translated to the appropriate number of sites that integration of HCV RNA on existing GenExperts could be piloted. Specific aims

• To evaluate ongoing projects of integrated HCV treatment services in harm reduction as well as primary care settings

• To evaluate the process of integration of HCV diagnostics with existing GenExpert equipment

• To evaluate case finding of 5000 people screened positive and not linked to care to understand their linkage to decentralized RNA testing at integrated GeneXpert sites Next step ! Decentralization of HIV diagnostics and treatment services in Georgia CDC TEPHINET MOH NCDC Thank you ! GHRN FIND Gilead

George Kamkamidze, MD, PhD, MS Head of Research Department, Health Research Union (HRU), Tbilisi, Georgia www.hru.ge

www.iasociety.org