The Management of Patients at High Risk of Serious COVID-19 Disease: Optimising the Patient Pathway in the Middle East, Africa, and Eastern Europe.

Introduction For patients at high risk of severe COVID-19 disease, antiviral therapeutic options are available to reduce the risk of hospitalization or death. Although many countries have developed national guidelines for COVID-19 management that include use of antiviral agents, it is unclear how these guidelines are used in daily clinical practice. This study aims to assess the management of high-risk COVID-19 patients in the Middle East, Africa, and Eastern Europe, with a focus on understanding current practices, challenges, and potential strategies for improvement. Methods Healthcare professionals (HCPs) from the Middle East, Africa, and Eastern Europe came together at a regional summit in February 2023 to share perspectives on the therapeutic management of patients at high risk of serious COVID-19 disease in the community. Summit participants represented diverse medical specialties, geographical regions, and healthcare settings. Key insights gathered during the summit were supplemented with evidence from the published literature via a non-systematic literature search of MEDLINE and online sources such as government reports since the start of 2020 to identify articles on disease burden, unmet needs, treatment access, antiviral therapy, guidelines related to individuals with COVID-19 at high-risk for poor outcomes in low- and middle-income countries (LMICs). Together, these sources were used by the authors to generate their recommendations for future priorities and optimal care pathways globally. Results Specific insights gathered from the summit were that participants reported that primary care is the first point of contact for high-risk patients, but the role of primary care physicians (PCPs) in treatment is uncertain. Additionally, participants highlighted that between-country differences in the care pathway for high-risk patients are due to variations in local treatment practices, healthcare system structures, and resourcing. In line with the published literature, participants agreed that HCP education is needed to support the identification, counseling, and appropriate management of high-risk patients and that pharmacists have a critical role to play in identifying clinically important potential interactions with antiviral treatment and recommending appropriate adjustments. Furthermore, patient hesitancy can result in late presentation, delayed treatment, and potential progression of symptoms. HCPs should proactively counsel high-risk patients, so they are aware of their risk and its implications and understand what to do if they experience symptoms of COVID-19. Targeted educational initiatives for patients are needed to mitigate reluctance to undergo COVID-19 testing and counter COVID-19 misinformation. Conclusion Collaboration among stakeholders is essential to optimize COVID-19 management for high-risk patients globally, ensuring effective implementation of guidelines and improving outcomes.

Differences in integrated assessment and management of non-communicable diseases (NCDs) for people with HIV across the WHO European region.

OBJECTIVES: We aimed to assess the extent of integration of non-communicable disease (NCD) assessment and management in HIV clinics across Europe. METHODS: A structured electronic questionnaire with 41 multiple-choice and rating-scale questions assessing NCD assessment and management was sent to 88 HIV clinics across the WHO European Region during March-May 2023. One response per clinic was collected. RESULTS: In all, 51 clinics from 34 countries with >100 000 people with HIV under regular follow-up responded. Thirty-seven clinics (72.6%) reported shared NCD care responsibility with the general practitioner. Systematic assessment for NCDs and integration of NCD management were common overall [median agreement 80%, interquartile range (IQR): 55-95%; and 70%, IQR: 50-88%, respectively] but were lowest in central eastern and eastern Europe. Chronic kidney disease (median agreement 96%, IQR: 85-100%) and metabolic disorders (90%, IQR: 75-100%) were regularly assessed, while mental health (72%, IQR: 63-85%) and pulmonary diseases (52%, IQR: 40-75%) were less systematically assessed. Some essential diagnostic tests such as glycated haemoglobin (HbA1c) for diabetes (n = 38/51, 74.5%), proteinuria for kidney disease (n = 30/51, 58.8%) and spirometry for lung disease (n = 11/51, 21.6%) were only employed by a proportion of clinics. The most frequent barriers for integrating NCD care were the lack of healthcare workers (n = 17/51, 33.3%) and lack of time during outpatient visits (n = 12/51, 23.5%). CONCLUSION: Most HIV clinics in Europe systematically assess and manage NCDs. People with HIV appear to be screened more frequently than the general population at the same age. There are, however, larger gaps among eastern European clinics in general and for clinics in all regions related to mental health, pulmonary diseases and the employment of some essential diagnostic tests.

Effect of remdesivir on mortality and the need for mechanical ventilation among hospitalized patients with COVID-19: real-world data from a resource-limited country.

OBJECTIVES: Georgia introduced remdesivir for the treatment of COVID-19 in December 2020. We evaluated the real-world effect of remdesivir on mortality and the need for mechanical ventilation among inpatients with COVID-19. METHODS: The study included 346 remdesivir recipients and 346 controls not receiving remdesivir selected through propensity score matching based on age, gender, presence of any chronic comorbid condition, and oxygen saturation at admission. Factors associated with in-hospital mortality and the need for mechanical ventilation were assessed in a multivariable logistic regression model. RESULTS: The groups were comparable by age, gender, comorbidities, and baseline oxygen saturation. Among 346 remdesivir recipients, 265 (76.6%) received a generic formulation of the drug. Eight (2.3%) patients died in the remdesivir group and 18 (5.2%) in the control group (P = 0.046). In the multivariable analysis, remdesivir was associated with non-statistically significant reduced odds of death (odds ratio: 0.39, 95% confidence interval: 0.14-1.04, P = 0.06). Significantly fewer patients in the remdesivir group required mechanical ventilation compared to controls: 2.9% vs 6.4% (P = 0.03). Statistically significant difference was maintained in multivariable analysis (odds ratio: 0.40, 95% confidence interval: 1.04-5.60, P = 0.04). CONCLUSION: Borderline reduction in the odds of death and statistically significant decrease in the need for mechanical ventilation support use of remdesivir in hospitalized patients with COVID-19.

Treatment of hepatitis C in primary health care in the country of Georgia.

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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.

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.

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.

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.

Regression of liver fibrosis over a 24-week period after completing direct-acting antiviral therapy in patients with chronic hepatitis C receiving care within the national hepatitis C elimination program in Georgia: results of hepatology clinic HEPA experience.

OBJECTIVE: We assessed the impact of direct-acting antiviral (DAA) therapy on liver fibrosis regression measured by transient elastography (TE) in patients with chronic hepatitis C virus (HCV) infection. PATIENTS AND METHODS: A prospective cohort study was carried out in HCV monoinfected patients with advanced liver fibrosis or cirrhosis receiving interferon (IFN)-containing or IFN-free DAA therapy. Liver stiffness (LS) score more than 14.5 kPa indicated LS-defined cirrhosis. The primary outcome was improvement in liver stiffness measurement (LSM) at week 24 after treatment measured as (a) decrease in the median LS compared with baseline and (b) at least a 20% decrease in LSM compared with baseline. A multivariate logistic regression model was utilized to identify the factors associated with at least a 20% improvement in LSM. RESULTS: Of a total of 304 patients, 172 (56.6%) had LS-defined cirrhosis before treatment. LSM decreased from the baseline median value of 16.9 (interquartile range: 11.8-27.7) kPa to a post-treatment week 24 score of 11.9 (interquartile range: 8.2-20.9) kPa (P<0.0001). Of a total of 304 patients, 198 (65.1%) achieved at least a 20% reduction in LS. In multivariate logistic regression analysis, sustained virological response (SVR) was associated significantly with this reduction (P<0.0001). The addition of IFN to the treatment regimen had no impact on the decrease in LSM. Despite decreasing baseline LSM, more than half of the LS-defined cirrhotic patients remained cirrhotic at week 24 after treatment. CONCLUSION: In patients with advanced fibrosis, pretreatment LS significantly reduced during DAA therapy. SVR was the only independent factor associated with the regression in LSM. However, irrespective of achieving SVR, liver damage still persisted in a substantial proportion of patients. Thus, early treatment of HCV-infected patients can significantly prevent residual liver damage.

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.

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.

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.

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.

Prevention of mother-to-child transmission of HIV: the Georgian experience.

OBJECTIVE: The objective of this paper is to review experience in prevention of mother-to-child transmission (PMTCT) of HIV in Georgia. BACKGROUND: PMTCT is one of the strategic priorities in Georgia. The first case of HIV infection in pregnant women was reported in 1999. Starting 2005 the National Programme on PMTCT became operational. MATERIALS AND METHODS: One hundred sixteen HIV voluntary counselling and testing (VCT) centers operate throughout the country at antenatal clinics. According to the National PMTCT protocol, all first time attending pregnant women are offered Voluntary Counselling and Testing (VCT). Testing on HIV/AIDS is based on identification of HIV antibodies by screening method and all positive results are referred to the Infectious Diseases, AIDS and Clinical Immunology Research Center (IDACIRC) for the further investigation (confirmation by Western Blot assay) and further management. Data collection was made retrospectively, using information from IDACIRC National HIV/AIDS Data Base, VRF for the period 1999-2007. RESULTS: Prevalence of HIV among pregnant women availing VCT services in 2006 was 0.03%. As of December, 2007 total 69 pregnancies of 64 women were registered at the IDACIRC. Fifty eight women (90.6%) acquired infection through heterosexual contact. None of the HIV positive women reported intravenous injection of illicit drugs. The majority of the HIV infected pregnant women had one sexual partner (90.6%). Of children delivered by 51 positive partners 41(80%) were infected through injecting drugs intravenously and 10 (20%) persons through heterosexual contacts. Throughout the period 1999-2007 14 pregnant women received PMTCT services only partially. In 2 cases children were HIV-infected. In 12 pregnancies women received AZT in about the 28th week of pregnancy. No case of HIV transmission to child was recorded in this group. In 32 cases pregnant women received full prophylaxis therapy and all children were negative for HIV infection. Among 6 pregnant women admitted at IDACIRC later than the 28th week of pregnancy only 1 child was infected. As of December 2007, 5 women are still pregnant. Three of them receive antiretroviral drugs (ARV) prophylaxis with AZT+3TC+SQV/r. Two women are under 28 weeks of gestational age. CONCLUSION: Over the last several years the national response to AIDS in Georgia achieved significant progress. The provision of comprehensive packages of PMTCT services in Georgia has been shown to minimize the risk of vertical transmission. As described above none of the women completing full course of ARV prophylaxis, combined with appropriate infant feeding, transmitted HIV to their children. PMTCT programmes are indisputably the main entry point not only for HIV related care and treatment for women, but also for other comprehensive care and prevention.