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.

Smoking and cessation-related attitudes among men who have sex with men in the country of Georgia.

Among men who have sex with men (MSM) in low- or middle-income countries, smoking and related factors have been understudied. We examined correlates of smoking status, level, and importance and confidence regarding quitting among 608 MSM in the country of Georgia recruited in June-September, 2016 (493 without HIV via peer referral in 3 Georgian cities; 115 with HIV via the National AIDS Center). Median age was 26 years, 78.6% reported current (past 30-day) alcohol use, and 22.4% reported past-year illicit drug use. Overall, 73.8% reported current smoking; of these, 87.1% smoked daily, mean cigarettes per day (cpd) was 19.8, 64.6% smoked ≤30 min of waking, and mean quitting importance and confidence were 6.8 and 6.4 (0 = not at all to 10 = extremely), respectively. Multivariable analyses indicated that current smoking correlated with past-month alcohol and past-year illicit drug use (p's < .001). Among smokers, cpd correlated with being older and smoking within 30 min of waking; greater quitting importance (≥7) correlated with higher education and no illicit substance use; and greater quitting confidence (≥7) was associated with fewer cpd, smoking ≤30 min of waking, and regional versus capital city residence. Given these findings, addressing tobacco and other substance use among MSM in Georgia is critical.

Tuberculosis, HIV, and viral hepatitis diagnostics in eastern Europe and central Asia: high time for integrated and people-centred services.

Globally, high rates (and in the WHO European region an increasing prevalence) of co-infection with tuberculosis and HIV and HIV and hepatitis C virus exist. In eastern European and central Asian countries, the tuberculosis, HIV, and viral hepatitis programmes, including diagnostic services, are separate vertical structures. In this Personal View, we consider underlying reasons for the poor integration for these diseases, particularly in the WHO European region, and how to address this with an initial focus on diagnostic services. In part, this low integration has reflected different diagnostic development histories, global funding sources, and sample types used for diagnosis (eg, typically sputum for tuberculosis and blood for HIV and hepatitis C). Cooperation between services improved as patients with tuberculosis needed routine testing for HIV and vice versa, but financial, infection control, and logistical barriers remain. Multidisease diagnostic platforms exist, but to be used optimally, appropriate staff training and sensible understanding of different laboratory and infection control risks needs rapid implementation. Technically these ideas are all feasible. Poor coordination between these vertical systems remains unhelpful. There is a need to increase political and operational integration of diagnostic and treatment services and bring them closer to patients.

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.

Cascade of care among HIV patients diagnosed in 2013 in Georgia: Risk factors for late diagnosis and attrition from HIV care.

INTRODUCTION: The major challenge in the HIV epidemic in Georgia is a high proportion of undiagnosed people living with HIV (estimated 48%) as well as a very high proportion of late presentations for care, with 66% presenting for HIV care with CD4 count <350 and 40% with <200 cells/mm3, in 2013. The objectives of this study was to evaluate patient engagement in the continuum of HIV care for HIV patients diagnosed in 2013 and, within this cohort, to evaluate factors associated with late diagnosis and attrition from care. METHODS: Factors associated with late diagnosis were analyzed through binary logistic regression. Exposure variables were the mode of HIV transmission (injecting drug use, male-to-male contact, and heterosexual contact), gender (male vs female), and age (categorized by median value ≤36 vs >36). In addition, CD4 count at diagnosis (cells/mm3) (≤350 or >350) together with all above factors were tested for the association with attrition through Poisson regression. RESULTS: Overall, 317 patients retained in care, representing 65% of those diagnosed (n = 488). Out of eligible 295 patients, 89.5% were on treatment and 84% of those viral load count was measured after 6 months of antiretroviral treatment initiation had HIV-1 viral load <1000 copies/mL. Patients reporting injecting drug use as a route-of HIV transmission had two times the odds (95% confidence interval = 1.34-3.49) to be diagnosed late and patients reporting male-to-male contact as a way of HIV transmission had half the odds (odds ratio = 0.46 (95% confidence interval = 0.26-0.81)) of late diagnosis compared to patients acquiring HIV through heterosexual contact. Patients older than 36 years were more likely to being diagnosed late. CONCLUSION: More attention should be given to injecting drug users as they represent the most at-risk population for late diagnosis together with older age and attrition.

Late presentation of HIV infection in the country of Georgia: 2012-2015.

Late presentation for HIV care has important individual and population implications. The objective of this study was to explore the problem of late presentation in the country of Georgia. Data on adult persons newly diagnosed with HIV in Georgia between 2012 and 2015 were extracted from the national AIDS Health Information System. Late presenter was defined as a person diagnosed with HIV with a CD4 cell count <350 cells/mm3 or an AIDS defining illness regardless of the CD4 cell count in the six months after HIV diagnosis. Late presenter with advanced disease was defined as a person diagnosed with HIV with a CD4 cell count <200 cells/mm3 or an AIDS defining illness, regardless of CD4 cell count in the six months after HIV diagnosis. Among 2267 adults diagnosed with HIV in Georgia in 2012-2015, 1987 (87.6%) had CD4 cell count measured within 6 months of HIV diagnosis and were included in the analysis. Among them 1260 (63.4%) patients were classified as late presenters and 870 (43.8%) as late presenters with advanced disease. The proportion of late presenters declined from 71.1% in 2012 to 55.5% in 2015 (p<0.0001), while presentation late with advanced disease decreased from 56.6% in 2012 to 34.5% in 2015 (p<0.0001). Late presentation was most common among people who inject drugs (77.7%). Overall 186 patients died over the studied period. Mortality was higher both among late presenters (6.74 per 100 person-years vs. 1.08 per 100 person-years, p<0.0001) and late presenters with advanced disease (8.93 per 100 person-years vs. 1.34 per 100 person-years, p<0.0001). High prevalence of late presentation in Georgia reflects insufficiency in HIV testing services. Better testing strategies are needed to improve earlier diagnosis and disease outcomes.

Progress Toward Achieving the UNAIDS 90-90-90 Goals in HIV Care From Diagnosis to Durable Viral Suppression in the Country of Georgia.

Successful engagement in HIV care is required to reach UNAIDS targets of 90-90-90. We analyzed routine programmatic data to quantify losses along the HIV care continuum in the country of Georgia. Analysis was limited to diagnosed persons and did not include estimated number of HIV-infected persons. Cascade of HIV care continuum was constructed for adult (age ≥18 years) HIV-infected persons newly diagnosed in Georgia in 2008-2012. Data were extracted from the national AIDS Health Information System as of June 30, 2014. Among 1,931 patients included, the median age was 37 years, 72% were men, and 40.7% had CD4 count <200 cells/mm3. A total of 1,711 (88.6%) were linked to care, 1,333 (69.0%) ever started antiretroviral therapy (ART), 1,044 (54.1%) ever achieved viral suppression, and 792 (41.0%) maintained viral suppression till the end of follow-up. Overall, 1,139 patients were lost from HIV diagnosis to maintaining viral suppression, including 761 (66.8%) patients who remained alive and 378 (33.2%) patients who died. Among 378 deceased patients, 324 (85.7%) died before achieving viral suppression after the median 3.5 months since diagnosis and 54 (14.3%) died after achieving viral suppression after the median 21.2 months since diagnosis. Among 761 alive patients without viral suppression, 297 (39.0%) were fully disengaged, 144 (18.9%) had never been prescribed ART, 161 (21.2) either never achieved suppression or discontinued ART, and 159 (20.9%) experienced rebound while on ART. Efforts are needed to improve earlier HIV diagnosis, to reduce the number of patients not in care, and to extend durability of viral suppression.

Significant Improvements Are Needed in HIV Care Continuum to Meet 90-90-90 Targets in Georgia.

The objective of this report was to assess Georgia's progress toward Joint United Nations Programme on HIV/AIDS 90-90-90 targets over the period between 2011 and 2015. The number of HIV-positive persons was estimated using Spectrum software. Number of persons diagnosed, on antiretroviral therapy (ART) and virally suppressed were quantified using data from the national AIDS health information system. By the end of 2015, out of the estimated 7100 persons living with HIV, 62% were diagnosed, 38% were on ART, and 32% were virally suppressed. There were improvements in each stage of cascade from 2011 to 2015: the proportion of diagnosed persons increased from 46% to 61%, ART coverage among diagnosed persons increased from 46% to 62%, and the proportion of virally suppressed patients among those on ART increased from 74% to 85%. Despite the progress, additional efforts are needed to reach the 90-90-90 targets. Reducing the number of people living with undiagnosed HIV will be critical for achieving goals.

Investigation of an outbreak of bloody diarrhea complicated with hemolytic uremic syndrome.

In July-August 2009, eight patients with bloody diarrhea complicated by hemolytic uremic syndrome (HUS) were admitted to hospitals in Tbilisi, Georgia. We started active surveillance in two regions for bloody diarrhea and post-diarrheal HUS. Of 25 case-patients who developed HUS, including the initial 8 cases, half were ⩾15 years old, 67% were female and seven (28%) died. No common exposures were identified. Among 20 HUS case-patients tested, Shiga toxin was detected in the stools of 2 patients (one with elevated serum IgG titers to several Escherichia coli serogroups, including O111 and O104). Among 56 persons with only bloody diarrhea, we isolated Shiga toxin-producing E. coli (STEC) O104:H4 from 2 and Shigella from 10; 2 had serologic evidence of E. coli O26 infection. These cases may indicate a previously unrecognized burden of HUS in Georgia. We recommend national reporting of HUS and improving STEC detection capacity.

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.

Estimating HIV incidence in eastern European country of Georgia: 2010-2012.

The knowledge of HIV incidence is essential to better understand patterns of HIV transmission. We estimated HIV incidence over 2010-2012 in the eastern European country of Georgia. Mathematical modeling using Spectrum software and assay-based recent infection testing algorithm were applied. The study included 1155 HIV patients newly diagnosed in 2010-2012 (84% of total diagnoses). Of them, 231 were determined to be recently infected on the recent infection testing algorithm. The proportion of recent cases did not differ between 2010, 2011 and 2012 (20.4% vs. 19.4% vs. 20.2%, p = 0.94). Both study methods derived comparable estimates ranging from 0.2 to 0.3%, which is up to twice as high as rates of new diagnosis reported in the same period. Despite the relatively stable HIV incidence over 2010-2012, the epidemic continues to grow because of the increasing gap between HIV-infected and diagnosed persons. Increased efforts are needed to reduce the number of people with undiagnosed HIV.

Mortality and causes of death among HIV-infected individuals in the country of Georgia: 1989-2012.

Since 2004, the country of Georgia has provided antiretroviral therapy (ART) to all patients in need. A nationwide retrospective cohort study was conducted to assess the effect of universal access to ART on patterns of mortality and causes of death among HIV-infected individuals in Georgia. All known HIV-infected adult individuals (age ≥18 years) diagnosed from 1989 through 2012 were included. Rates and causes of death were determined using routinely collected data from the national HIV/AIDS database. Causes of death were classified according to the Coding of Death in HIV (CoDe) protocol. Between 1989 and 2012, 3,554 HIV-infected adults were registered in Georgia contributing to 13,572 person-years (PY) of follow-up. A total of 779 deaths were registered during follow-up. The mortality rate peaked in 2004 with 10.74 deaths per 100 PY (95% CI: 7.92-14.24) and significantly decreased after the universal availability of ART to 4.02 per 100 PY (95% CI: 3.28-4.87) in 2012. In multivariate analysis the strongest predictor of mortality was having AIDS at the time of HIV diagnosis (hazard ratio: 5.69, 95% CI: 4.72-6.85). AIDS-related diseases accounted for the majority of deaths (n=426, 54.7%). Tuberculosis (TB) was the leading cause of death accounting for 21% of the total deaths reported. Universal access to ART significantly reduced mortality among HIV-infected patients in Georgia. However, overall mortality rates remain high primarily due to late diagnosis, and TB remains a significant cause of death. Improving rates of early HIV diagnosis and ART initiation may further decrease mortality as well as prevent new HIV and TB infections.

Genomic comparison of Escherichia coli O104:H4 isolates from 2009 and 2011 reveals plasmid, and prophage heterogeneity, including shiga toxin encoding phage stx2.

In May of 2011, an enteroaggregative Escherichia coli O104:H4 strain that had acquired a Shiga toxin 2-converting phage caused a large outbreak of bloody diarrhea in Europe which was notable for its high prevalence of hemolytic uremic syndrome cases. Several studies have described the genomic inventory and phylogenies of strains associated with the outbreak and a collection of historical E. coli O104:H4 isolates using draft genome assemblies. We present the complete, closed genome sequences of an isolate from the 2011 outbreak (2011C-3493) and two isolates from cases of bloody diarrhea that occurred in the Republic of Georgia in 2009 (2009EL-2050 and 2009EL-2071). Comparative genome analysis indicates that, while the Georgian strains are the nearest neighbors to the 2011 outbreak isolates sequenced to date, structural and nucleotide-level differences are evident in the Stx2 phage genomes, the mer/tet antibiotic resistance island, and in the prophage and plasmid profiles of the strains, including a previously undescribed plasmid with homology to the pMT virulence plasmid of Yersinia pestis. In addition, multiphenotype analysis showed that 2009EL-2071 possessed higher resistance to polymyxin and membrane-disrupting agents. Finally, we show evidence by electron microscopy of the presence of a common phage morphotype among the European and Georgian strains and a second phage morphotype among the Georgian strains. The presence of at least two stx2 phage genotypes in host genetic backgrounds that may derive from a recent common ancestor of the 2011 outbreak isolates indicates that the emergence of stx2 phage-containing E. coli O104:H4 strains probably occurred more than once, or that the current outbreak isolates may be the result of a recent transfer of a new stx2 phage element into a pre-existing stx2-positive genetic background.

Outcomes of Universal Access to Antiretroviral Therapy (ART) in Georgia.

Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm(3). During followup, 152 (20%) patients died, with the majority of deaths occurring within 12 months of ART initiation. Mortality was associated with advanced immunodeficiency or the presence of incurable disease at baseline. Among patients remaining on treatment, the median CD4 gain was 216 cell/mm(3) and 86% of patients had viral load <400 copies/ml at the last clinical visit. The Georgia ART program has been successful in treating injection drug users infected with HIV.

Experience of antiretroviral treatment in Georgia.

INTRODUCTION: HIV infection is the major public health, social and economic problem in Georgia. Although the HIV epidemic is in its nascent phase in the country, the potential risk for development of a wide spread HIV epidemic is very high. The aim of this study is to evaluate the effectiveness of ARV treatment principles in Georgia, including treatment and monitoring methods. MATERIALS AND METHODS: The study included 985 people living with HIV/AIDS in Georgia registered at Infectious Disease, AIDS and Clinical Immunology Research Center since 2004. To ensure universal access to ARV therapy all HIV/AIDS individuals included in the study were investigated by special algorithm, all identified patients requiring ARV therapy were offered treatment and monitored during therapy on treatment effectiveness and side effects. HIV-1 RNA in plasma was measured by quantitative Polymerase Chain Reaction. For determination of percentages and absolute count of T-lymphocyte subpopulations single-platform immunophenotyping technique using the Becton-Dickinson FACSCalibur flow cytometer was applied. For resistance testing TRUGENE HIV-1 Genotyping Kit with the OpenGene DNA Sequencing System (Siemens) was used. Reasons of treatment failure and mortality rate among ARV treated patients were analyzed. RESULTS AND CONCLUSIONS: Treatment was offered to 398 HIV/AIDS patients. 397 patients started treatment, 1 patient refused. Out of 397 HIV/AIDS patients treated 21 patients discontinued, 54 patients died and 322 patients are currently on ARV treatment. Out of the treated patients 281 adults and 11 children are receiving first-line treatment, 27 adults and 2 children are on second-line treatment and 1 adult is receiving salvage regimen. Treatment failure was defined in 52 cases. Among them immunological failure was observed in 7 cases, clinical failure in 1 case and virologic failure in 44 cases. Prevalence of drug resistance among virologic failure cases accounted for 73% and inadequate adherence for 27% cases. Out of drug resistance cases 3% has three-class drug resistance, 84%--two-class drug resistance and 13% found to be resistant to one class. In ARV naive patients the prevalence of drug resistance to any class was 4.33%. The majority of death cases among ARV treated patients was due to non-AIDS related or incurable conditions, while deaths due to AIDS related conditions were mainly associated with delayed referral of patients in already advanced stage of disease. It's worth to mention that the highest number of death cases was due to liver failure in HIV/HCV and/or HBV co-infected patients.