Browsing by Author "Chkhartishvili, Nikoloz (25227423400)"

Background: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. Methods: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. Results: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17–1·38), raltegravir (1·37, 1·20–1·56), and tenofovir alafenamide (1·38, 1·22–1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91–2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47–1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96–0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19–1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15–1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52–2·11, and 1·70, 1·44–2·01, respectively). Interpretation: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. Funding: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences. © 2021 Elsevier Ltd

Background: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. Methods: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. Results: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17–1·38), raltegravir (1·37, 1·20–1·56), and tenofovir alafenamide (1·38, 1·22–1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91–2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47–1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96–0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19–1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15–1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52–2·11, and 1·70, 1·44–2·01, respectively). Interpretation: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. Funding: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences. © 2021 Elsevier Ltd

Objectives: Although direct-acting antivirals (DAAs) can clear HCV in nearly all HIV/HCV-coinfected individuals, high rates of reinfection may hamper efforts to eliminate HCV in this population. We investigated reinfection after sustained virological response (SVR) in HIV/HCV-coinfected individuals in Europe. Methods: Factors associated with odds of reinfection by 2 years after SVR in EuroSIDA participants with one or more HCV-RNA test and 2 years follow-up were assessed using logistic regression. Results: Overall, 1022 individuals were included. The median age was 50 (interquartile range: 43–54 years), and most were male (78%), injection drug users (52%), and received interferon (IFN)-free DAAs (62%). By 24 months, 75 [7.3%, 95% confidence interval (CI): 5.7–8.9%] individuals were reinfected. Among individuals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN-free and IFN-based therapy. After adjustment, individuals who had started treatment during or after 2014 with IFN-free or IFN-based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11–0.38; 0.43, 95% CI: 0.22–0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis. Conclusions: Among HIV/HCV-coinfected individuals in Europe, 7.3% were reinfected with HCV within 24 months of achieving SVR, with evidence suggesting that this is decreasing over time and with use of newer HCV regimens. Harm reduction to reduce reinfection and surveillance to detect early reinfection with an offer of treatment are essential to eliminate HCV. © 2021 British HIV Association.

Objectives: The aim of this survey was to describe the current status of HIV care in the countries of Central and Eastern Europe and to investigate how close the region is to achieving the UNAIDS 2020 target of 90–90–90. Methods: In 2014, data were collected from 24 Central and Eastern European countries using a 38-item questionnaire. Results: All countries reported mandatory screening of blood and organ donors for HIV. Other groups subjected to targeted screening included people who inject drugs (PWID) (15/24, 62.5%), men who have sex with men (MSM) (14/24, 58.3%), and sex workers (12/24, 50.0%). Only 14 of the 24 countries (58.3%) screened pregnant women. The percentages of late presentation and advanced disease were 40.3% (range 14–80%) and 25.4% (range 9–50%), respectively. There was no difference between countries categorized by income or by region in terms of the percentages of persons presenting late or with advanced disease. The availability of newer antiretroviral drugs (rilpivirine, etravirine, darunavir, maraviroc, raltegravir, dolutegravir) tended to be significantly better with a higher country income status. Ten countries reported initiating antiretroviral therapy (ART) regardless of CD4+ T cell count (41.7%), five countries (20.8%) used the threshold of <500 cells/μl, and nine countries (37.5%) used the threshold of <350 cells/μl. Initiation of ART regardless of the CD4+ T cell count was significantly more common among high-income countries than among upper-middle-income and lower-middle-income countries (100% vs. 27.3% and 0%, respectively; p = 0.001). Drugs were provided free of charge in all countries and mostly provided by governments. There were significant discrepancies between countries regarding the follow-up of people living with HIV. Conclusions: There are major disparities in the provision of HIV care among sub-regions in Europe, which should be addressed. More attention in terms of funding, knowledge and experience sharing, and capacity building is required for the resource-limited settings of Central and Eastern Europe. The exact needs should be defined and services scaled up in order to achieve a standard level of care and provide an adequate and sustainable response to the HIV epidemic in this region. © 2018 The Authors

Background:Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study.Methods:HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m2] between HCV strata.Results:Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results.Conclusion:This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings. © 2020 Lippincott Williams and Wilkins. All rights reserved.

Background:Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study.Methods:HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m2] between HCV strata.Results:Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results.Conclusion:This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings. © 2020 Lippincott Williams and Wilkins. All rights reserved.

Objectives: Survey was conducted to assess state of viral hepatitis care in Central and Eastern Europe (CEE). Methods: Representatives of 16 CEE countries completed on-line survey in April–May 2017 that collected information on basic epidemiology and availability of key services for HCV and HBV infections. Sources of information provided ranged from national surveillance data to expert opinion. Results: The burden of viral hepatitis varied between countries, ranging from 6,500 to 2 million for HCV and from 10,000 to 3 million for HBV. Access to routine HCV RNA testing and genotyping was reported by 11 and 9 countries, respectively. HCV resistance testing was available in 7 countries. Direct acting antivirals (DAAs) were available in 13 countries, most frequently Sofosbuvir and Ledipasvir/Sofosbuvir (12 countries apiece) and Ombitasvir/Paritaprevir/Dasabuvir (9 countries). HBV DNA testing and HBV genotyping were routinely available in 10 and 7 countries, respectively. Eleven countries reported available treatment with Tenofovir. Conclusions: There are gaps in viral hepatitis care in CEE. Despite the availability of registered modern drugs for HCV and HBV, the access to treatment is limited. Ensuring quality health care is essential to reduce the epidemic and achieve the WHO’s goal of eliminating viral hepatitis as a major public health challenge. © 2019, Czech National Institute of Public Health. All rights reserved.