Association of Treated and Untreated Chronic Hepatitis C With the Incidence of Active Tuberculosis Disease: A Population-Based Cohort Study.

BACKGROUND: Hepatitis C virus (HCV) infection causes dysregulation and suppression of immune pathways involved in the control of tuberculosis (TB) infection. However, data on the role of chronic hepatitis C as a risk factor for active TB are lacking. We sought to evaluate the association between HCV infection and the development of active TB. METHODS: We conducted a cohort study in Georgia among adults tested for HCV antibodies (January 2015-September 2020) and followed longitudinally for the development of newly diagnosed active TB. Data were obtained from the Georgian national programs of hepatitis C and TB. The exposures of interest were untreated and treated HCV infection. A Cox proportional hazards model was used to calculate adjusted hazard ratios (aHRs). RESULTS: A total of 1 828 808 adults were included (median follow-up time: 26 months; IQR: 13-39 months). Active TB was diagnosed in 3163 (0.17%) individuals after a median of 6 months follow-up (IQR: 1-18 months). The incidence rate per 100 000 person-years was 296 among persons with untreated HCV infection, 109 among those with treated HCV infection, and 65 among HCV-negative persons. In multivariable analysis, both untreated (aHR = 2.9; 95% CI: 2.4-3.4) and treated (aHR = 1.6; 95% CI: 1.4-2.0) HCV infections were associated with a higher hazard of active TB, compared with HCV-negative persons. CONCLUSIONS: Adults with HCV infection, particularly untreated individuals, were at higher risk of developing active TB disease. Screening for latent TB infection and active TB disease should be part of clinical evaluation of people with HCV infection, especially in high-TB-burden areas.

Hepatitis C care cascade among patients with and without tuberculosis: Nationwide observational cohort study in the country of Georgia, 2015-2020.

BACKGROUND: The Eastern European country of Georgia initiated a nationwide hepatitis C virus (HCV) elimination program in 2015 to address a high burden of infection. Screening for HCV infection through antibody testing was integrated into multiple existing programs, including the National Tuberculosis Program (NTP). We sought to compare the hepatitis C care cascade among patients with and without tuberculosis (TB) diagnosis in Georgia between 2015 and 2019 and to identify factors associated with loss to follow-up (LTFU) in hepatitis C care among patients with TB. METHODS AND FINDINGS: Using national ID numbers, we merged databases of the HCV elimination program, NTP, and national death registry from January 1, 2015 to September 30, 2020. The study population included 11,985 adults (aged ≥18 years) diagnosed with active TB from January 1, 2015 through December 31, 2019, and 1,849,820 adults tested for HCV antibodies between January 1, 2015 and September 30, 2020, who were not diagnosed with TB during that time. We estimated the proportion of patients with and without TB who were LTFU at each step of the HCV care cascade and explored temporal changes. Among 11,985 patients with active TB, 9,065 (76%) patients without prior hepatitis C treatment were tested for HCV antibodies, of which 1,665 (18%) had a positive result; LTFU from hepatitis C care was common, with 316 of 1,557 (20%) patients with a positive antibody test not undergoing viremia testing and 443 of 1,025 (43%) patients with viremia not starting treatment for hepatitis C. Overall, among persons with confirmed viremic HCV infection, due to LTFU at various stages of the care cascade only 28% of patients with TB had a documented cure from HCV infection, compared to 55% among patients without TB. LTFU after positive antibody testing substantially decreased in the last 3 years, from 32% among patients diagnosed with TB in 2017 to 12% among those diagnosed in 2019. After a positive HCV antibody test, patients without TB had viremia testing sooner than patients with TB (hazards ratio [HR] = 1.46, 95% confidence intervals [CI] [1.39, 1.54], p < 0.001). After a positive viremia test, patients without TB started hepatitis C treatment sooner than patients with TB (HR = 2.05, 95% CI [1.87, 2.25], p < 0.001). In the risk factor analysis adjusted for age, sex, and case definition (new versus previously treated), multidrug-resistant (MDR) TB was associated with an increased risk of LTFU after a positive HCV antibody test (adjusted risk ratio [aRR] = 1.41, 95% CI [1.12, 1.76], p = 0.003). The main limitation of this study was that due to the reliance on existing electronic databases, we were unable to account for the impact of all confounding factors in some of the analyses. CONCLUSIONS: LTFU from hepatitis C care after a positive antibody or viremia test was high and more common among patients with TB than in those without TB. Better integration of TB and hepatitis C care systems can potentially reduce LTFU and improve patient outcomes both in Georgia and other countries that are initiating or scaling up their nationwide hepatitis C control efforts and striving to provide personalized TB treatment.

Economic evaluation of the Hepatitis C virus elimination program in the country of Georgia, 2015 to 2017.

BACKGROUND AND AIMS: In 2015, the country of Georgia launched an elimination program aiming to reduce the prevalence of Hepatitis C virus (HCV) infection by 90% from 5.4% prevalence (~150 000 people). During the first 2.5 years of the program, 770 832 people were screened, 48 575 were diagnosed with active HCV infection, and 41 483 patients were treated with direct-acting antiviral (DAA)-based regimens, with a >95% cure rate. METHODS: We modelled the incremental cost-effectiveness ratio (ICER) of HCV screening, diagnosis and treatment between April 2015 and November 2017 compared to no treatment, in terms of cost per quality-adjusted life year (QALY) gained in 2017 US dollars, with a 3% discount rate over 25 years. We compared the ICER to willingness-to-pay (WTP) thresholds of US$4357 (GDP) and US$871 (opportunity cost) per QALY gained. RESULTS: The average cost of screening, HCV viremia testing, and treatment per patient treated was $386 to the provider, $225 to the patient and $1042 for generic DAAs. At 3% discount, 0.57 QALYs were gained per patient treated. The ICER from the perspective of the provider including generic DAAs was $2285 per QALY gained, which is cost-effective at the $4357 WTP threshold, while if patient costs are included, it is just above the threshold at $4398/QALY. All other scenarios examined in sensitivity analyses remain cost-effective except for assuming a shorter time horizon to the end of 2025 or including the list price DAA cost. Reducing or excluding DAA costs reduced the ICER below the opportunity-cost WTP threshold. CONCLUSIONS: The Georgian HCV elimination program provides valuable evidence that national programs for scaling up HCV screening and treatment for achieving HCV elimination can be cost-effective.

Retreatment of Chronic Hepatitis C Infection: Real-World Regimens and Outcomes From National Treatment Programs in Three Low- and Middle-Income Countries.

Access to recommended second-line treatments is limited for patients who fail initial hepatitis C virus (HCV) therapy in low- and middle-income countries. Alternative regimens and associated outcomes are not well understood. Through a pooled analysis of national program data in Egypt, Georgia, and Myanmar, we observed SVR rates >90% for alternative retreatment regimens.

Three Years of Progress Toward Achieving Hepatitis C Elimination in the Country of Georgia, April 2015-March 2018.

BACKGROUND: In April 2015, in collaboration with the US Centers for Disease Control and Prevention and Gilead Sciences, the country of Georgia embarked on the world's first hepatitis C elimination program. We aimed to assess progress toward elimination targets 3 years after the start of the elimination program. METHODS: We constructed a hepatitis C virus (HCV) care cascade for adults in Georgia, based on the estimated 150 000 persons aged ≥18 years with active HCV infection. All patients who were screened or entered the treatment program during April 2015-March 2018 were included in the analysis. Data on the number of persons screened for HCV were extracted from the national HCV screening database. For the treatment component, we utilized data from the Georgia National HCV treatment program database. Available treatment options included sofosbuvir and ledipasvir/sofosbuvir-based regimens. RESULTS: Since April 2015, a cumulative 974 817 adults were screened for HCV antibodies; 86 624 persons tested positive, of whom 61 925 underwent HCV confirmatory testing. Among the estimated 150 000 adults living with chronic hepatitis C in Georgia, 52 856 (35.1%) were diagnosed, 45 334 (30.2%) initiated treatment with direct-acting antivirals, and 29 090 (19.4%) achieved a sustained virologic response (SVR). Overall, 37 256 persons were eligible for SVR assessment; of these, only 29 620 (79.5%) returned for evaluation. The SVR rate was 98.2% (29 090/29 620) in the per-protocol analysis and 78.1% (29 090/37 256) in the intent-to-treat analysis. CONCLUSIONS: Georgia has made substantial progress in the path toward eliminating hepatitis C. Scaling up of testing and diagnosis, along with effective linkage to treatment services, is needed to achieve the goal of elimination.

Progress and challenges of a pioneering hepatitis C elimination program in the country of Georgia.

BACKGROUND & AIMS: Georgia, with a high prevalence of HCV infection, launched the world's first national hepatitis C elimination program in April 2015. A key strategy is the identification, treatment, and cure of the estimated 150,000 HCV-infected people living in the country. We report on progress and key challenges from Georgia's experience. METHODS: We constructed a care cascade by analyzing linked data from the national hepatitis C screening registry and treatment databases during 2015-2018. We assessed the impact of reflex hepatitis C core antigen (HCVcAg) testing on rates of viremia testing and treatment initiation (i.e. linkage to care). RESULTS: As of December 31, 2018, 1,101,530 adults (39.6% of the adult population) were screened for HCV antibody, of whom 98,430 (8.9%) tested positive. Of the individuals who tested positive, 78,484 (79.7%) received viremia testing, of whom 66,916 (85.3%) tested positive for active HCV infection. A total of 52,576 people with active HCV infection initiated treatment and 48,879 completed their course of treatment. Of the 35,035 who were tested for cure (i.e., sustained virologic response [SVR]), 34,513 (98.5%) achieved SVR. Reflex HCVcAg testing, implemented in March 2018, increased rates of monthly viremia testing by 97.5% among those who screened positive for anti-HCV, however, rates of treatment initiation decreased by 60.7% among diagnosed viremic patients. CONCLUSIONS: Over one-third of people living with HCV in Georgia have been detected and linked to care and treatment, however, identification and linkage to care of the remaining individuals with HCV infection is challenging. Novel interventions, such as reflex testing with HCVcAg, can improve rates of viremia testing, but may result in unintended consequences, such as decreased rates of treatment initiation. Linked data systems allow for regular review of the care cascade, allowing for identification of deficiencies and development of corrective actions. LAY SUMMARY: This report describes progress in Georgia's hepatitis C elimination program and highlights efforts to promote hepatitis C virus screening and treatment initiation on a national scale. Georgia has made progress towards eliminating hepatitis C, treating over 50,000 people, approximately one-third of the number infected, and achieving cure for 98.5% of those tested. However, identifying infected individuals and linking them to care remains challenging. Novel approaches to increase diagnostic testing can have unintended consequences further down the care cascade.

Treatment outcomes of patients with chronic hepatitis C receiving sofosbuvir-based combination therapy within national hepatitis C elimination program in the country of Georgia.

BACKGROUND: Georgia has one of the highest HCV prevalence in the world and launched the world's first national HCV elimination programs in 2015. Georgia set the ambitious target of diagnosing 90% of people living with HCV, treating 95% of those diagnosed and curing 95% of treated patients by 2020. We report outcomes of Sofosbuvir (SOF) based treatment regimens in patients with chronic HCV infection in Georgia. METHODS: Patients with cirrhosis, advanced liver fibrosis and severe extrahepatic manifestations were enrolled in the treatment program. Initial treatment consisted of SOF plus ribavirin (RBV) with or without pegylated interferon (INF). Sustained virologic response (SVR) was defined as undetectable HCV RNA at least 12 weeks after the end of treatment. SVR were calculated using both per-protocol and modified intent-to-treat (mITT) analysis. Results for patients who completed treatment through 31 October 2018 were analyzed. RESULTS: Of the 7342 patients who initiated treatment with SOF-based regimens, 5079 patients were tested for SVR. Total SVR rate was 82.1% in per-protocol analysis and 74.5% in mITT analysis. The lowest response rate was observed among genotype 1 patients (69.5%), intermediate response rate was achieved in genotype 2 patients (81.4%), while the highest response rate was among genotype 3 patients (91.8%). Overall, SOF/RBV regimens achieved lower response rates than IFN/SOF/RBV regimen (72.1% vs 91.3%, P < 0.0001). In multivariate analysis being infected with HCV genotype 2 (RR =1.10, CI [1.05-1.15]) and genotype 3 (RR = 1.14, CI [1.11-1.18]) were associated with higher SVR. Patients with cirrhosis (RR = 0.95, CI [0.93-0.98]), receiving treatment regimens of SOF/RBV 12 weeks, SOF/RBV 20 weeks, SOF/RBV 24 weeks and SOF/RBV 48 weeks (RR = 0.85, CI [0.81-0.91]; RR = 0.86, CI [0.82-0.92]; RR = 0.88, CI [0.85-0.91] and RR = 0.92, CI [0.87-0.98], respectively) were less likely to achieve SVR. CONCLUSIONS: Georgia's real world experience resulted in high overall response rates given that most patients had severe liver damage. Our results provide clear evidence that SOF plus IFN and RBV for 12 weeks can be considered a treatment option for eligible patients with all three HCV genotypes. With introduction of next generation DAAs, significantly improved response rates are expected, paving the way for Georgia to achieve HCV elimination goals.

Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia.

Human immunodeficiency virus (HIV) drug resistance is a major threat to the sustained impact of antiretroviral therapy (ART). We studied the epidemiology of drug resistance in the country of Georgia. The study included all adult patients who experienced virologic failure on first line ART and received HIV drug resistance testing between 2005 and 2016. The Stanford HIV Sequence Database was used for interpretation of the resistance data. Patient-level data were extracted from the national AIDS health information system. Of the 447 patients included, 85.5% harbored the subtype A6 virus, 8.0% - subtype B, 2.9% - subtype G, and other subtypes were <1%. The most frequent first-line regimens were Tenofovir/Emtricitabine/Efavirenz (28.4%), Zidovudine/Lamivudine/Efavirenz (28.4%), and Abacavir/Lamivudine/Efavirenz (15.9%). A total of 85.0% of the patients with treatment failure developed at least one drug resistance mutation affecting their susceptibility to ART. The most frequent nucleoside reverse transcriptase inhibitor mutations were M184V (65.3%), K65R (19.7%) and L74V (17.0%). At least three thymidine analogue mutations were detected in 6.3% of the patients. From non-nucleoside reverse transcriptase inhibitor mutations, G190S was shown to be the most prevalent (49.4%), followed by K101E (27.10%) and K103N (24.4%). G190S and K101E were more common in subtype A as compared with non-A viruses (G190S: 54.9% vs 11.3%, P < 0.0001; K101E: 29.8% vs 11.3%, P = 0.005). On the other hand, K103N was more frequent in non-A subtypes (43.4%) compared with subtype A (22.2%), P = 0.0008. A majority of persons failing on ART had HIV drug resistance. Drug resistance patterns may vary by subtype. K65R mutation remains below 20%, but given the high use of Tenofovir in the country, continuing surveillance of drug resistance is needed.

Progress in Testing for and Treatment of Hepatitis C Virus Infection Among Persons Who Inject Drugs - Georgia, 2018.

In April 2015, the country of Georgia, with a high prevalence of hepatitis C virus (HCV) infection (5.4% of the adult population, approximately 150,000 persons), embarked on the world's first national elimination program (1,2). Nearly 40% of these infections are attributed to injection drug use, and an estimated 2% of the adult population currently inject drugs, among the highest prevalence of injection drug use in the world (3,4). Since 2006, needle and syringe programs (NSPs) have been offering HCV antibody testing to persons who inject drugs and, since 2015, referring clients with positive test results to the national treatment program. This report summarizes the results of these efforts. Following implementation of the elimination program, the number of HCV antibody tests conducted at NSPs increased from an average of 3,638 per year during 2006-2014 to an average of 21,551 during 2015-2018. In 2017, to enable tracking of clinical outcomes among persons who inject drugs, NSPs began encouraging clients to voluntarily provide their national identification number (NIN), which all citizens must use to access health care treatment services. During 2017-2018, a total of 2,780 NSP clients with positive test results for HCV antibody were identified in the treatment database by their NIN. Of 494 who completed treatment and were tested for HCV RNA ≥12 weeks after completing treatment, 482 (97.6%) were cured of HCV infection. Following the launch of the elimination program, Georgia has made much progress in hepatitis C screening among persons who inject drugs; recent data demonstrate high cure rates achieved in this population. Testing at NSPs is an effective strategy for identifying persons with HCV infection. Tracking clients referred from NSPs through treatment completion allows for monitoring the effectiveness of linkage to care and treatment outcomes in this population at high risk, a key to achieving hepatitis C elimination in Georgia. The program in Georgia might serve as a model for other countries.

An evaluation of the hepatitis C testing, care and treatment program in the country of Georgia's corrections system, December 2013 - April 2015.

BACKGROUND: The country of Georgia has a high burden of chronic hepatitis C virus (HCV) infection, and prisoners are disproportionately affected. During 2013, a novel program offering no cost screening and treatment of HCV infection for eligible prisoners was launched. METHODS: The HCV treatment program implemented a voluntary opt-in anti-HCV testing policy to all prisoners. Anti-HCV positive persons received HCV RNA and genotype testing. Transient elastography was also performed on prisoners with positive HCV RNA results. Prisoners with chronic HCV infection who had ≥F2 Metavir stage for liver fibrosis and a prison sentence ≥ 6 months were eligible for interferon-based treatment, which was the standard treatment prior to 2015. We conducted an evaluation of the HCV treatment program among prisoners from the program's inception in December 2013 through April 2015 by combining data from personal interviews with corrections staff, prisoner data in the corrections database, and HCV-specific laboratory information. RESULTS: Of an estimated 30,000 prisoners who were incarcerated at some time during the evaluation period, an estimated 13,500 (45%) received anti-HCV screening, of whom 5175 (38%) tested positive. Of these, 3840 (74%) received HCV RNA testing, 2730 (71%) tested positive, and 880 (32%) met treatment eligibility. Of these, 585 (66%) enrolled; 405 (69%) completed treatment, and 202 (50%) achieved a sustained virologic response at least 12 weeks after treatment completion. CONCLUSIONS: HCV infection prevalence among Georgian prisoners was high. Despite challenges, we determined HCV treatment within Georgian Ministry of Correction facilities was feasible. Efforts to address HCV infection among prison population is one important component of HCV elimination in Georgia.

Impact of hepatitis C virus recombinant form RF1_2k/1b on treatment outcomes within the Georgian national hepatitis C elimination program.

AIM: Hepatitis C virus (HCV) recombinant form RF1_2k/1b is common in ethnic Georgians. This chimera virus contains genomic fragments of genotype 2 and genotype 1 and is misclassified as genotype 2 by standard genotyping. We aimed to identify RF1_2k/1b strains among genotype 2 patients and assess its impact on treatment outcomes. METHODS: The study included 148 patients with HCV genotype 2 as determined by 5-untranslated region/core genotyping assay. RF1_2k/1b was identified by sequencing the non-structural protein 5B region. Patients were treated within the national hepatitis C elimination program with sofosbuvir/ribavirin (SOF/RBV), interferon (IFN)/SOF/RBV, or ledipasvir (LDV)/SOF/RBV. RESULTS: Of 148 patients, 103 (69.5%) had RF1_ 2k/1b. Sustained virologic response (SVR) data was available for 136 patients (RF1_ 2k/1b, n = 103; genotype 2, n = 33). Sustained virologic response was achieved in more genotype 2 patient than in RF1_2k/1b patients (97.0% vs. 76.7%, P = 0.009). Twelve weeks of LDV/SOF/RBV treatment was highly effective (100% SVR) in both genotypes. Among RF1_2k/1b patients, LDV/SOF/RBV for 12 weeks was superior (100% SVR) to SOF/RBV for 12 weeks (56.4%, P < 0.0001) or 20 weeks (79.2%, P = 0.05). Twelve weeks of IFN/SOF/RBV also showed better response than SOF/RBV for 12 weeks (88.9% vs. 56.4%, P = 0.02) in these patients. CONCLUSIONS: High prevalence of the RF1_2k/1b strain can significantly affect treatment outcomes. Treatment with IFN/SOF/RBV and especially LDV/SOF/RBV ensured significantly higher SVR in patients infected with RF1_2k/1b strain compared to standard HCV genotype 2 treatment with SOF/RBV. There is a need to reassess existing methods for the management of HCV genotype 2 infections, especially in areas with high prevalence of the RF1_2k/1b strain.

The Role of Screening and Treatment in National Progress Toward Hepatitis C Elimination - Georgia, 2015-2016.

Georgia, a country in the Caucasus region of Eurasia, has a high prevalence of hepatitis C virus (HCV) infection. In April 2015, with technical assistance from CDC, Georgia embarked on the world's first program to eliminate hepatitis C, defined as a 90% reduction in HCV prevalence by 2020 (1,2). The country committed to identifying infected persons and linking them to care and curative antiviral therapy, which was provided free of charge through a partnership with Gilead Sciences (1,2). From April 2015 through December 2016, a total of 27,595 persons initiated treatment for HCV infection, among whom 19,778 (71.7%) completed treatment. Among 6,366 persons tested for HCV RNA ≥12 weeks after completing treatment, 5,356 (84.1%) had no detectable virus in their blood, indicative of a sustained virologic response (SVR) and cure of HCV infection. The number of persons initiating treatment peaked in September 2016 at 4,595 and declined during October-December. Broader implementation of interventions that increase access to HCV testing, care, and treatment for persons living with HCV are needed for Georgia to reach national targets for the elimination of HCV.

The natural history of recent hepatitis C virus infection among blood donors and injection drug users in the country of Georgia.

INTRODUCTION: Hepatitis C virus (HCV) infection is a serious health problem in Georgia. METHODS: We conducted a prospective study to identify and characterize the natural history of recent HCV infection since very first days of infection. Recent HCV infection was defined as detectable plasma HCV RNA in the absence of anti-HCV antibodies. RESULTS: A total of 7600 HCV seronegative blood donors and 3600 HCV seronegative drug users were screened for recent HCV infection. Among them 7 (0.09 %) blood donors and 10 (0.28 %) drug users tested positive for HCV RNA and were classified as having recent HCV infection. Of these 17 patients 4 (23.5 %) spontaneously cleared the virus by the end of 24 week follow-up. Five clinical forms of recent HCV infection were identified during the follow-up. Four patients had symptomatic disease, including 3 patients with jaundice and other clinical symptoms (2 of them cleared virus) and 1 patient only had other symptoms without jaundice. All symptomatic patients had ALT elevation. Three distinct variants of asymptomatic disease were identified in 13 patients: 9 patients had ALT elevation and none cleared the virus; 2 patients developed chronic disease without ALT elevation; 2 patients cleared virus without anti-HCV seroconversion and without ALT elevation; this form can be described as transitory HCV viremia. CONCLUSION: Additional studies are needed to define clinical and public health implications of transitory HCV viremia. Our study suggests the need for implementing nucleic acid testing of blood donors and key populations in order to more effectively identify HCV infected persons.

National Progress Toward Hepatitis C Elimination - Georgia, 2015-2016.

The country of Georgia has a high prevalence of hepatitis C virus (HCV) infection, associated with exposures to HCV in health care settings with inadequate infection control and unsafe injections among persons who inject drugs (1). In April 2015, in collaboration with CDC and other partners, Georgia embarked on a program to eliminate HCV infection, subsequently defined as achieving a 90% reduction in prevalence by 2020. The initial phase of the program focused on providing HCV treatment to infected persons with advanced liver disease and at highest risk for HCV-associated morbidity and mortality. By April 27, 2016, a total of 27,392 HCV-infected persons registered for the program, 8,448 (30.8%) started treatment, and 5,850 patients (69.2%) completed HCV treatment. Among patients completing treatment who were eligible for posttreatment testing, 2,398 received polymerase chain reaction (PCR) testing for HCV at least 12 weeks after completion of treatment; 1,980 (82.6%) had no detectable virus, indicative of a sustained virologic response* (i.e., cure). Major challenges to achieving elimination remain, including the need to increase access to care and treatment services and implement a comprehensive approach to prevention and control of HCV infection. As a global leader in this effort, the Georgia HCV Elimination Program can help pave the way for other countries experiencing high rates of HCV infection to undertake similar initiatives.

Launch of a Nationwide Hepatitis C Elimination Program--Georgia, April 2015.

Hepatitis C virus (HCV) infects an estimated 130-150 million persons globally and results in an estimated 700,000 deaths annually from hepatocellular carcinoma or cirrhosis. Georgia, a middle-income Eurasian country, has one of the highest estimated HCV prevalences in the world. In 2011, Georgia began offering treatment to a limited number of HCV-infected persons. Beginning in 2013, when new oral medications that can cure >90% of HCV infections were licensed, Georgia engaged partners to develop a comprehensive HCV prevention and control plan, during which the concept of elimination of HCV transmission and disease emerged. To prepare for the launch of an HCV elimination program, Georgia requested CDC's assistance to describe HCV epidemiology, evaluate laboratory and health care capacity, and conduct program monitoring and evaluation. This report describes the activities undertaken to prepare for the program, launched in April 2015, and early results of its initial phase, focused on improving access to affordable diagnostics and free curative treatment for HCV-infected persons with severe liver disease. A national population-based serosurvey began in May 2015, and four clinical sites and their laboratories were selected as initial pilot sites; since June, three additional sites have been added. Through July 3, 2015, a total of 6,491 persons sought treatment, and 6,177 (95.2%) initiated diagnostic work-up. Among these, 1,519 (24.6%) completed work-up, 1,474 (97.0%) of whom initiated treatment. Georgia is scaling up capacity to meet the demand for HCV treatment and is collaborating with CDC and other partners on development of a comprehensive HCV elimination plan that includes specific goals and activities needed to achieve them.

High incidence of the hepatitis C virus recombinant 2k/1b in Georgia: Recommendations for testing and treatment.

AIM: The first hepatitis C virus (HCV) recombinant, RF2k/1b, was initially described from Russia and has since then been identified from patients in Ireland, Estonia, Uzbekistan and Cyprus. Many of these patients originated from Georgia; however, there is no information on its prevalence in Georgia or its susceptibility to antiviral treatment. METHODS: We retrospectively sequenced the non-structural region 5B (NS5B) of the HCV genome in samples from 72 Georgian patients, 36 of whom had been treated with pegylated interferon and ribavirin. RESULTS: The HCV genotype was determined using the Versant HCV Genotype v2 kit. Based on this typing, 32 patients (44.4%) were infected with genotype 1, 21 (29.1%) genotype 2 and 19 (26.3%) genotype 3. Partial NS5B of these strains was sequenced and analyzed for type, with concordant genotype results for all type 1 and 3 strains. Discrepant results were observed for genotyped 2 strains, with 16 (76%) having NS5B of subtype 1b. On phylogenetic analysis, 15 NS5B sequences of these strains were found in a clade formed by recombinant RF2k/1b strains. The remaining discordant sequence was found within a clade formed by 1b strains. CONCLUSION: Our findings show that the RF2k/1b recombinant strain is common among Georgian patients previously assumed to be infected with genotype 2. Because genotyping is mainly performed to decide treatment strategies, there is a need to determine the genotype by analysis of at least two genomic regions in strains from Georgian patients considered infected with genotype 2 based on standard HCV genotyping methods.

Virologic outcomes of second-line antiretroviral therapy in Eastern European country of Georgia.

BACKGROUND: Data on the effectiveness of second-line antiretroviral therapy (ART) in resource-limited countries of Eastern Europe is limited. Objective of this study was to evaluate virological outcomes of second-line ART in Georgia. METHODS: We conducted retrospective analysis using routinely available program data. Study included adult HIV-infected patients with confirmed HIV drug resistance, who were switched to second-line ART from August 2005 to December 2010. Patients were followed until July 1, 2011. Primary outcome was achievement of viral suppression. Demographic, clinical, laboratory and adherence data were abstracted from medical and program records. Adherence was expressed as percentage based on medication refill data, and was calculated as days supply of medications dispensed divided by days between prescription fills. Predictors of primary outcome were assessed in modified Poisson regression analysis. RESULTS: A total of 84 patients were included in the study. Among them 71.4% were men and 62% had history of IDU. All patients were receiving non-nucleoside reverse transcriptase based regimen as initial ART. The mean 6-month adherence prior to virologic failure was 75%, with 31% of patients showing 100% adherence. All patients were switched to protease inhibitor based regimens. Patients were followed for median 27 months. Over this period 9 (10.7%) patients died. Among 80 patients remaining alive at least 6 month after ART regimen switch, 72 (90%) patients ever reached undetectable viral load. The mean first 6-month adherence on second-line treatment was 81%, with 47.5% of patients showing 100% adherence. The proportion of patients achieving viral suppression after 6, 12, 24 and 36 months of second-line ART did not vary significantly ranging from 79 to 83%. Percentage of IDUs achieving viral suppression ranged from 75% and 83%. Factors associated with failure to achieve viral suppression at 6-months of second-line ART were: adherence <80% (Risk ratio [RR] 5.09, 95% CI: 1.89-13.70) and viral load >100,000 at the time of treatment failure (RR 3.39, 95% CI: 1.46-7.89). CONCLUSIONS: The study demonstrated favourable virological outcomes of the second-line ART in Georgia. Majority of patients, including IDUs, achieved sustained virological response over 36 month period. The findings highlight the need of improving adherence.

Characterization of HIV-1 subtypes and drug resistance mutations among individuals infected with HIV in Georgia.

In order to describe HIV-1 subtypes and drug resistance mutations in Georgia, blood samples from 153 patients infected with HIV-1 collected from 2006 to 2008 were genotyped. Of these, 126 samples were from newly diagnosed, antiretroviral (ARV)-naïve patients and 27 from ARV-treated patients. Partial pol region sequences were used to identify drug resistance mutations and to conduct phylogenetic analysis for subtype determination. The results indicated that 138 (90.2%) patients harbored subtype A viruses, 11 (7.2%) carried subtype B virus, two subtype G (1.3%), one (0.6%) subtype F and one (0.6%) 03_AB recombinant. All subtype A strains clustered with the Former Soviet Union A (A FSU) subtype. Among patients with no prior exposure to ARVs, mutations associated with resistance were detected in five patients: three (2.4%) patients had reverse transcriptase (RT) inhibitor mutations and two other patients had the protease (PI) inhibitor associated mutation M46I. PI mutation V77I was found in 42 of subtype A isolates. Of 27 ARV-treated patients, 22 (81.5%) harbored at least one nucleoside reverse transcriptase inhibitors (NRTI), a non-NRTI (NNRTI) and/or a PI mutation. The most common NRTI resistance mutation was M184V/I (74.1%). Frequency of thymidine analog mutations was relatively low (25.9%). With regard to NNRTI mutations, G190S/A was the most frequent mutation, which might be a preferred mutations for subtype A. Georgia's HIV epidemic continues to be dominated by Subtype A FSU. The prevalence of transmitted drug resistance is low, but has the potential to increase with increasing use of ARVs.

The prevalence of hyperglycemia and its impact on mortality among people living with HIV in Georgia.

BACKGROUND: Life expectancy and quality of life of people living with HIV have been dramatically improved after introducing antiretroviral therapy, and the prevalence of non-communicable diseases has increased. Several studies have found that hyperglycemia with or without type 2 diabetes was associated with poor outcomes in people living with HIV. The study's objective was to determine the prevalence of hyperglycemia and assess its impact on mortality. MATERIALS AND METHODS: A retrospective cohort study was conducted among people living with HIV diagnosed in 2012-2018 and followed through 2020 at the Infectious Diseases, AIDS and Clinical Immunology Research Center in Tbilisi, Georgia. Primary outcomes of interest included the prevalence of hyperglycemia and mortality. Causes of death were classified according to the Coding of Death in HIV (CoDe) protocol. RESULTS: Our study included 2914 people living with HIV. Two hundred and forty-two (8.3%) patients had hyperglycemia, with an increasing prevalence by age. Three hundred one (9.7%) participants died over the median 3.71 (IQR: 2.14-5.37) years of follow-up. Among these, 139 (46.2%) were due to AIDS- related causes, 123 (40.9%)-were due to non-AIDS causes, and in 39 (12.9%) cases, the cause of death could not be determined. Overall, the cohort contributed to 11,148 person-years of follow-up (PYFU), translating into a mortality rate of 2.70 deaths per 100 PYFU. The mortality rate was significantly higher among individuals with hyperglycemia-11.17 deaths per 100 PYFU vs 2.07 deaths per 100 PYFU among normoglycemic patients(p<0.0001). CONCLUSIONS: Hyperglycemia was associated with increased odds of mortality. Screening and management of hyperglycemia should be integrated into routine HIV clinical services as part of a comprehensive care package.