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.

Poor agreement between interferon-gamma release assays and the tuberculin skin test among HIV-infected individuals in the country of Georgia.

BACKGROUND: Improved tests to diagnose latent TB infection (LTBI) are needed. We sought to evaluate the performance of two commercially available interferon-gamma release assays (IGRAs) compared to the tuberculin skin test (TST) for the diagnosis of LTBI and to identify risk factors for LTBI among HIV-infected individuals in Georgia, a country with high rates of TB. METHODS: HIV-patients were enrolled from the National AIDS Center in Tbilisi, Georgia. After providing informed consent, each participant completed a questionnaire, had blood drawn for QuantiFERON-TB Gold in-Tube (QFT-GIT) and T-SPOT.TB testing and had a TST placed. The TST was read at 48-72 hrs with ≥ 5 mm induration considered positive. RESULTS: Between 2009-2011, 240 HIV-infected persons (66% male) with a median age of 38 years and a median CD4 count of 255 cells/µl (IQR: 124-412) had diagnostic testing for LTBI performed. 94% had visible evidence of a BCG scar. The TST was positive in 41 (17%) patients; QFT-GIT in 70 (29%); and T-SPOT.TB in 56 (24%). At least one diagnostic test was positive in 109 (45%) patients and only among 13 (5%) patients were all three tests positive. Three (1%) QFT-GIT and 19 (8%) T-SPOT.TB test results were indeterminate. The agreement among all pairs of tests was poor: QFT-GIT vs. T-SPOT.TB (κ = 0.18, 95% CI .07-.30), QFT-GIT vs. TST (κ = 0.29, 95% CI .16-.42), and TST vs. T-SPOT.TB (κ = 0.22, 95% CI .07-.29). Risk factors for LTBI varied by diagnostic test and none showed associations between positive test results and well-known risk factors for TB, such as imprisonment, drug abuse and immunological status. CONCLUSIONS: A high proportion of HIV patients had at least one positive diagnostic test for LTBI; however, there was very poor agreement among all tests. This lack of agreement makes it difficult to know which test is superior and most appropriate for LTBI testing among HIV-infected patients. While further follow-up studies will help determine the predictive ability of different LTBI tests, improved modalities are needed for accurate detection of LTBI and assessment of risk of developing active TB among HIV-infected patients.

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.

Causes and outcomes of hospitalizations among people living with HIV in Georgia's referral institution, 2012-2017.

We assessed trends in causes and outcomes of hospitalization among people living with HIV (PLWH) admitted to the Infectious Diseases, AIDS and Clinical Immunology Research Center (IDACIRC) in Tbilisi, Georgia. Retrospective analysis included adult PLWH admitted to IDACIRC for at least 24 h. Internationally validated categorization was used to split AIDS admissions into mild, moderate, and severe AIDS. A total of 2085 hospitalizations among 1123 PLWH were registered over 2012-2017 with 65.1% (731/1123) of patients presenting with CD4 count <200. Of 2085 hospitalizations, 931 (44.7%) were due to AIDS-defining illnesses. In 2012, AIDS conditions accounted for 50.3% of admissions compared to 41.6% in 2017 (p = 0.16). Overall, 167 hospitalizations (8.0%) resulted in lethal outcome. AIDS admissions had higher mortality than non-AIDS admissions (11.5% vs 5.2%, p < 0.0001). Among 167 deceased patients, 137 (82.0%) had CD4 count <200 at admission. In multivariate analysis, factors significantly associated with mortality included severe AIDS versus non-AIDS admission (OR 2.81, 95% CI: 1.10-7.15), CD4 cell counts <50 (OR 4.34, 95% CI: 2.52-7.47), and 50-100 (OR 2.37, 95% CI: 1.27-4.42) versus >200. Active AIDS disease remains a significant cause of hospitalization and fatal outcome in Georgia. Earlier diagnosis of HIV is critical for decreasing AIDS hospitalizations and mortality.

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.

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.