HIV treatment strategies across Central, Eastern and Southeastern Europe: New times, old problems.

INTRODUCTION: In the last decade, substantial differences in the epidemiology of, antiretroviral therapy (ART) for, cascade of care in and support to people with HIV in vulnerable populations have been observed between countries in Western Europe, Central Europe (CE) and Eastern Europe (EE). The aim of this study was to use a survey to explore whether ART availability and therapies have evolved in CE and EE according to European guidelines. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group conducted two identical multicentre cross-sectional online surveys in 2019 and 2021 concerning the availability and use of antiretroviral drugs (boosted protease inhibitors [bPIs], integrase inhibitors [INSTIs] and nucleoside reverse transcriptase inhibitors [NRTIs]), the introduction of a rapid ART start strategy and the use of two-drug regimens (2DRs) for starting or switching ART. We also investigated barriers to the implementation of these strategies in each region. RESULTS: In total, 18 centres participated in the study: four from CE, six from EE and eight from Southeastern Europe (SEE). Between those 2 years, older PIs were less frequently used and darunavir-based regimens were the main PIs (83%); bictegravir-based and tenofovir alafenamide-based regimens were introduced in CE and SEE but not in EE. The COVID-19 pandemic did not significantly interrupt delivery of ART in most centres. Two-thirds of centres adopted a rapid ART start strategy, mainly in pregnant women and to improve linkage of care in vulnerable populations. The main obstacle to rapid ART start was that national guidelines in several countries from all three regions did not support such as strategy or required laboratory tests first; an INSTI/NRTI combination was the most commonly prescribed regimen (75%) and was exclusively prescribed in SEE. 2DRs are increasingly used for starting or switching ART (58%), and an INSTI/NRTI was the preferred regimen (75%) in all regions and exclusively prescribed in SEE, whereas the use of bPIs declined. Metabolic disorders and adverse drug reactions were the main reasons for starting a 2DR; in the second survey, HIV RNA <500 000 c/ml and high cluster of differentiation (CD)-4 count emerged as additional important reasons. CONCLUSIONS: In just 2 years and in spite of the emergence of the COVID-19 pandemic, significant achievements concerning ART availability and strategies have occurred in CE, EE and SEE that facilitate the harmonization of those strategies with the European AIDS Clinical Society guidelines. Few exceptions exist, especially in EE. Continuous effort is needed to overcome various obstacles (administrative, financial, national guideline restrictions) in some countries.

Living with HIV during COVID-19: knowledge and worry about COVID-19, adherence to COVID-19-related precautions, and HIV health outcomes.

The COVID-19 pandemic has been profound impacts on mental and physical health of individuals with chronic diseases. Thus, it is important to understand the effects of the COVID-19 pandemic on people living with HIV. We aimed to assess the association between COVID-19-related knowledge and worry, HIV-related health practices and outcomes, and adherence to precautions related to COVID-19, and possible associations of these factors with HIV treatment outcomes (ART adherence and viral load). A cross-sectional survey was conducted between October 2020 and February 2021 among 291 PLWH at two large university hospital HIV clinics in Izmir, Turkey. Additionally, the most recent HIV-RNA load, CD4 count was recorded using medical records. Logistic regression analyses were performed to determine predictors of self-reported adherence to COVID-19-related precautions, ART adherence and undetectable viral load. COVID-19-related worry, COVID-19-related knowledge, and ART adherence were significant predictors of adherence to COVID-19-related precautions. Furthermore, adherence to COVID-19-related precautions was a significant predictor of both ART adherence and undetectable viral load. Findings provide a unique aspect of the interrelations of COVID and living with HIV. Since health behaviors and outcomes for COVID-19 and HIV seem to be interrelated, treatment practices and interventions that address these simultaneously may enhance their efficacy.

Awareness and acceptability of monkeypox vaccine in men who have sex with men.

Background/aim: To determine the knowledge about and acceptance level of monkeypox vaccine in men who have sex with men (MSM). Materials and methods: A 14-item questionnaire, developed by the European Centers for Disease Control (ECDC), was presented online to MSM, aged ≥18 years old, via smartphone applications (Grindr and Hornet), between June 30th and August 12th, 2022. Results: Of the 737 participants who completed the survey, 678 were born in Türkiye and 59 were migrants/visitors born in different countries. All of the participants were living in Türkiye. The median age was 31 (range 18-68) years. Overall, 21.9% were HIV-positive, 94.9% were using antiretroviral therapy (ART), 3.9% reported using preexposure prophylaxis (PrEP), 9.9% had been diagnosed with a sexually transmitted infection (STI) in the past 12 months, and 10.1% reported using chemicals during sexual intercourse in the past three months.Participants aged 45-54 were significantly more concerned about being treated differently due to monkeypox than those in the other age groups (p = 0.038). Compared to the participants who were HIV-negative, those who were HIV-positive were significantly more worried about acquiring monkeypox (34.1% were very worried and 43.6% were worried, p = 0.033), were more likely to definitely or probably get vaccinated if offered (67.6% and 80.6%, respectively, p = 0.002), and were more concerned about being exposed to different attitudes due to monkeypox (37.0% and 53.3%, respectively, p < 0.01). Among those using ART, 82.3% and 50.0% reported that they would definitely or probably get vaccinated if offered, respectively (p = 0.046). There were no significant differences between groups for the remaining parameters. Conclusion: Despite the low level of knowledge about monkeypox, the majority of the participants reported that they believed in the vaccine's efficacy. Those who were HIV-positive were particularly more concerned about monkeypox and were more willing to protect themselves compared to those who were HIV-negative.

Retrospective evaluation of an observational cohort by the Central and Eastern Europe Network Group shows a high frequency of potential drug-drug interactions among HIV-positive patients receiving treatment for coronavirus disease 2019 (COVID-19).

OBJECTIVES: The aim of this international multicentre study was to review potential drug-drug interactions (DDIs) for real-life coadministration of combination antiretroviral therapy (cART) and coronavirus disease 2019 (COVID-19)-specific medications. METHODS: The Euroguidelines in Central and Eastern Europe Network Group initiated a retrospective, observational cohort study of HIV-positive patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data were collected through a standardized questionnaire and DDIs were identified using the University of Liverpool's interaction checker. RESULTS: In total, 524 (94.1% of 557) patients received cART at COVID-19 onset: 117 (22.3%) were female, and the median age was 42 (interquartile range 36-50) years. Only 115 (21.9%) patients were hospitalized, of whom 34 required oxygen therapy. The most frequent nucleoside reverse transcriptase inhibitor (NRTI) backbone was tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide (TAF) with lamivudine or emtricitabine (XTC) (79.3%) along with an integrase strand transfer inhibitor (INSTI) (68.5%), nonnucleoside reverse transcriptase inhibitor (NNRTI) (17.7%), protease inhibitor (PI) (13.7%) or other (2.5%). In total, 148 (28.2%) patients received COVID-19-specific treatments: corticosteroids (15.7%), favipiravir (7.1%), remdesivir (3.1%), hydroxychloroquine (2.7%), tocilizumab (0.6%) and anakinra (0.2%). In total, 62 DDI episodes were identified in 58 patients (11.8% of the total cohort and 41.9% of the COVID-19-specific treatment group). The use of boosted PIs and elvitegravir accounted for 43 DDIs (29%), whereas NNRTIs were responsible for 14 DDIs (9.5%). CONCLUSIONS: In this analysis from the Central and Eastern European region on HIV-positive persons receiving COVID-19-specific treatment, it was found that potential DDIs were common. Although low-dose steroids are mainly used for COVID-19 treatment, comedication with boosted antiretrovirals seems to have the most frequent potential for DDIs. In addition, attention should be paid to NNRTI coadministration.

Sexual transmission of infections across Europe: appraising the present, scoping the future.

Objectives: Our journal partnered with the Europe section of the International Union against STI (IUSTI) at a workshop held at the 18th European AIDS Conference in London on 30 October 2021. The workshop reviewed epidemiological trends and discussed STI care provision within HIV services across Europe. Methods and Results: We started by highlighting trends in bacterial STIs reported to the European Centre for Disease Prevention and Control from countries in the European Union/European Economic Area. This showed that notifications of bacterial STIs reached an all-time high in 2019, but are expected to be impacted by the COVID-19 pandemic in 2020-2021. We then reviewed the evolving relationship between STIs and HIV and pointed out how antiretroviral treatment and pre-exposure prophylaxis remain highly effective against HIV transmission despite the rising incidence of STIs. Within emerging concepts in STIs, we appraised the benefits and risks of asymptomatic screening for chlamydia, and also considered the potential perils of routinely testing for agents that lack a defined role in disease. Finally, we discussed standards of STI care for people living with HIV, informed by a brief survey of IUSTI Europe country representatives and members of the Euroguidelines in Central and Eastern Europe network. Conclusions: The survey indicated substantial variability and identified key improvement targets: fighting barriers to effective service provision and access, increasing diagnostic capability and taking leadership in driving up the quality of care. We must not forget the STI-related needs of the many people who will be living with HIV for decades into the future.

[Should Tetanus Vaccine Booster be Given Earlier in Individuals Living with HIV?] / HIV ile Yasayan Bireylerde Tetanos Asisinin Rapeli Daha Erken Yapilmali Mi?

The incidence rate of tetanus has dramatically decreased following the discovery of the tetanus vaccine. A decennial booster dose is necessary to maintain the protective antibody levels after the primary vaccination schedule. The recommendations for the tetanus booster doses in adult "people living with acquired immune deficiency virus (HIV)" (PLWH) is similar to those for the general population. However, the duration of protective antibodies in PLWH is unknown. The aim of this study was to determine the factors affecting the response of HIV-infected individuals to tetanus vaccine and to evaluate the role of tetanus antitoxin level in determining the timing of the booster dose. PLWH attending the Adult Vaccination Unit of Ege University Faculty of Medicine Infectious Diseases and Clinical Microbiology Department were tested for tetanus antibodies from 30 October to 30 November 2020. Demographic information and the history of primary vaccination and booster doses were derived from medical files. Tetanus antibodies were detected with "enzyme immunoassay (EIA)" method with Clostridium tetani toxin 5S IgG-"enzyme linked immunosorbent assay (ELISA)" kit (Nova Lisa, Novatec Immundiagnostica, Germany). Antibody levels <0.01 IU/ml were considered negative, 0.01-0.5 IU/ml weak positive, 0.51-1.0 IU/ml positive and > 1.1 IU/ml strong positive. A level ≥ 0.50 IU/ml was considered as protective. The study included 146 PLWH [men (n= 126) and women (n= 40)]. The mean age was 39.5 ± 11.20 years (range: 18-65). Protective antibody level was detected in 114 (78.1%) participants. Receiver operating characteristics (ROC) analysis revealed that the ideal lower limit of CD4+ T cell count during booster vaccination for a person to develop protective antibody level was calculated as ≥ 218 cell/mm3. In the multivariate analysis, it was found that age <50 years (OR= 16.4, 95% CI= 4.9-55.2), the absence of AIDS at the time of diagnosis (OR= 6.7, 95% Cl= 1.05-17.4) and CD4+ T cell count ≥ 218 cells/mm3 at the time of vaccination (OR= 4.2, 95% CI= 1.05-17.4) were associated with protective levels of antibody. Protective levels of tetanus antibodies in PLWH are lower than the general population. It should be considered that the booster dose may be required earlier, especially in PLWH who are > 50 years old, with CD4+ T lymphocyte count <200 cells/mm3 during previous booster vaccination and who had AIDS at the time of the diagnosis.

Investigation of drug resistance against protease, reverse transcriptase, and integrase inhibitors by next-generation sequencing in HIV-positive patients.

Our aim was to investigate the mutations in protease (PR), reverse transcriptase (RT), and integrase (IN) gene regions in human immunodeficiency virus (HIV) using a single amplicon via next-generation sequencing (NGS). The study included plasma samples from 49 HIV-1-positive patients, which were referred for HIV-1 drug resistance testing during 2017. A nested polymerase chain reaction (PCR) was performed after the RNA extraction and one-step reverse transcription stages. The sequencing of the HIV genome in the PR, RT, and IN gene regions was carried out using MiSeq NGS technology. Sanger sequencing (SS) was used to analyze resistance mutations in the PR and RT gene regions using a ViroSeq HIV-1 Genotyping System. PCR products were analyzed with an ABI3500 GeneticAnalyzer (Applied Biosystems). Resistance mutations detected with NGS at frequencies above 20% were identical to the SS results. Resistance to at least one antiretroviral (ARV) drug was 22.4% (11 of 49) with NGS and 10.2% (5 of 49) with SS. At least one low-frequency resistance mutation was detected in 18.3% (9 of 49) of the samples. Low-frequency resistance mutations resulted in virological failure in only one patient. The cost of the analyses was reduced by sample pooling and multiplex analysis using the MiSeq system. This is the first study in Turkey to use NGS technologies for the detection of resistance mutations in all three gene (PR, RT, IN) regions using a single amplicon. Our findings suggest that NGS is more sensitive and cost-effective than the SS method.

Programmatic mapping and size estimation of female sex workers, transgender sex workers and men who have sex with men in Istanbul and Ankara, Turkey.

OBJECTIVES: Despite a growing HIV threat, there is no definition and characterisation of key populations (KPs), who could be the major drivers of the epidemic in Turkey. We used programmatic mapping to identify locations where KPs congregate, estimate their numbers and understand their operational dynamics to develop appropriate HIV programme implementation strategies. METHODS: Female and transgender sex workers (FSWs and TGSWs), and men who have sex with men (MSM) were studied in Istanbul and Ankara. Within each district, hot spots were identified by interviewing key informants and a crude spot list in each district was developed. The spot validation process was led by KP members who facilitated spot access and interviews of KPs associated with that spot. Final estimates were derived by aggregating the estimated number of KPs at all spots, which was adjusted for the proportion of KPs who visit multiple spots, and for the proportion of KPs who do not visit spots. RESULTS: FSWs were the largest KP identified in Istanbul with an estimate of 30 447 (5.8/1000 women), followed by 15 780 TGSWs (2.9/1000 men) and 11 656 MSM (2.1/1000). The corresponding numbers in Ankara were 9945 FSWs (5.2/1000 women), 1770 TGSWs (1/1000 men) and 5018 MSM (2.5/1000 men). Each KP had unique typologies based on the way they find and interact with sex partners. MSM were mostly hidden and a higher proportion operated through internet and phone-based applications. Night time was the peak time with Friday, Saturday and Sunday being the peak days of activity in both Istanbul and Ankara. CONCLUSIONS: This study has highlighted the presence of a substantial number of FSWs, TGSW and MSM in Istanbul and Ankara. The information obtained from this study can be used to set priorities for resource allocation and provide HIV prevention services where coverage could be the highest.

Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011-2017.

BACKGROUND: There is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The aim of this study was to evaluate the discontinuation of first ART before and after the availability of better tolerated and less complex regimens by comparing the frequency, reasons and associations with patient characteristics. METHODS: A total of 3019 ART-naive patients registered in the HIV-TR cohort who started ART between Jan 2011 and Feb 2017 were studied. Only the first modification within the first year of treatment for each patient was included in the analyses. Reasons were classified as listed in the coded form in the web-based database. Cumulative incidences were analysed using competing risk function and factors associated with discontinuation of the ART regimen were examined using Cox proportional hazards models and Fine-Gray competing risk regression models. RESULTS: The initial ART regimen was discontinued in 351 out of 3019 eligible patients (11.6%) within the first year. The main reason for discontinuation was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and provider preference (5.4%). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based (aHR = 4.4, [95% CI 3.0-6.4]; p < 0.0001) or protease inhibitor (PI)-based regimens (aHR = 4.3, [95% CI 3.1-6.0]; p < 0.0001) relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017) (aHR = 0.6, [95% CI 0.4-0.9]; p < 0.0001) was less likely to be discontinued. A lower rate of treatment discontinuation for intolerance/toxicity was observed with InSTI-based regimens (2.0%) than with NNRTI- (6.6%) and PI-based regimens (7.5%) (p < 0.001). The percentage of patients who achieved HIV RNA < 200 copies/mL within 12 months of ART initiation was 91% in the ART discontinued group vs. 94% in the continued group (p > 0.05). CONCLUSION: ART discontinuation due to intolerance/toxicity and virologic failure decreased over time. InSTI-based regimens were less likely to be discontinued than PI- and NNRTI-based ART.

The deep impact of the COVID-19 pandemic on medical students: An online cross-sectional study evaluating Turkish students' anxiety.

AIM: Coronavirus Disease 2019 (COVID-19) changed the delivery of medical education in Turkey by moving to an emergency remote teaching system and led to many challenges for future doctors. In this study, we aimed to explore the impact of the COVID-19 pandemic on medical students, to assess their anxiety level and their main anxiety sources related to this pandemic. METHODS: A Google Form was distributed to medical students using the virtual snowball sampling method. The form included the Beck Anxiety Inventory and additional 19 questions on sociodemographic characteristics, perceived level of knowledge about the epidemic, self-risk perceptions of COVID-19 and their anxiety levels about some other topics related to COVID-19. RESULTS: Overall, 3105 medical students with a mean age of 22.37 ± 2.46, took the survey. Amongst the participants, only 32% of the students defined their knowledge about the precautions that should be taken during an epidemic disease as acceptable. Students reported highest anxiety level for the continuing spread of COVID-19 in Turkey and transmitting coronavirus to another person. Clinically significant anxiety prevalence was 23.2%. Regression analysis revealed that factors that increased the risk of being anxious included being female, being other than a 5th-year student, thinking that being a medical student would increase the risk of coronavirus transmission or being uncertain about it, being exposed to a patient with COVID-19 or being uncertain about it, being anxious about the continuing spread of COVID-19 in Turkey, being anxious about acquiring COVID-19, being anxious for graduating and being on active duty, being anxious about a medical training interruption. CONCLUSION: Our results suggest that anxiety is prevalent amongst Turkish medical students during the COVID-19 pandemic and they have a weak preparedness for a pandemic such as COVID-19. Based on our results, new strategies should be implemented for medical education and for alleviating students' anxiety levels.

[Friend or Foe? Evaluation of BCG Vaccine and Latent Tuberculosis Infection Effect in Patients Diagnosed with COVID-19 Infection]. / Dost mu Düsman mi? COVID-19 Enfeksiyonu Tanili Hastalarda BCG Asisi ve Latent Tüberküloz Enfeksiyonu Etkisinin Degerlendirilmesi.

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide, some issues such as the uncertainty of the disease progress, whether intensive care will be needed, and risk classification are still important for clinicians. It is notable that in countries where latent tuberculosis infection (LTBI) is common and participating in the national Bacillus Calmette-Guerin (BCG) vaccination program, the case-fatality rates are relatively low throughout the world. In this study, it was aimed to evaluate the effects of the BCG vaccine and LTBI status on the course of the disease in patients diagnosed with coronavirus-19 (COVID-19) infection and to compare the LTBI rate with people with and without COVID-19 infection. The patients diagnosed with COVID-19 infection who were hospitalized during a period of seven months between May 1st to December 1st, 2020 were investigated by the QuantiFERON-TB Gold Plus (QFT-Plus) test in the blood samples for the presence of LTBI. For the comparison of the patients diagnosed with COVID-19 and people without COVID-19 infections in terms of LTBI rate retrospectively; all consecutive patients who were sent blood samples to the mycobacteriology laboratory for the QFT-Plus test between January 2016 and December 2019 were included in the study. Demographic, clinical, radiological, laboratory, and follow-up data of the patients were obtained from the electronic patient file. A total of 170 patients (n= 9 8 male [57.6%], n= 72 female [42.3%], mean age= 53.5 ± 15.8 years) were enrolled. Twenty-five patients' (25/170 [14.7%]) QFT-plus tests were positive. When the cases with positive QFT-Plus test (n= 25) and the cases with negative QFT-Plus test (n = 145) were compared in terms of disease severity respectively; it was determined that mild/moderate patients were 18/25 (72%) and 108/145 (74.5%), severe patients were 7/25 (28%) and 37/145 (25.5%) (p= 0.988). When these two groups were compared in terms of the clinical course respectively; the need for intensive care was 6/25 (24%) and 34/145 (23.4%) (p= 1.00), oxygen therapy requirement was 13/25 (52%) and 49/145 (33.8%) (p= 0.128), and death was 5/25 (20%) and 18/145 (12.4%) (p= 0.341). QFT-Plus positivity was 25/170 (14.7%) in patients diagnosed with COVID-19, while in control group it was 198/496 (39.9%) (OR= 0.259, 95% CI [0.164-0.411], p<0.001). When the values were evaluated quantitatively, in the COVID-19 patient group, QFT-Plus T1/T2 (IU/ml) interferon (IFN)-É£ was 0.87 ± 1.52/0.62 ± 1.53, while in the control group it was 1.52 ± 3.69/1.50 ± 3.33 (p= 0.032, p= 0.04). There was no significant difference in the parameters investigated between 82 (48.2%) patients with BCG vaccine and those 88 (51.8%) without BCG vaccine. Although it was not statistically significant in our study, increased oxygen therapy requirement and higher mortality rates in the QFT-Plus positive group were remarkable. The detection of statistically significantly lower LTBI rates and T1-T2/IFN-É£ values in the COVID-19 group supported that SARS-CoV-2 infection may suppress lymphocyte functions in patients and IFN-É£ response. We believe that the results of our study are remarkably valuable, but more clinical studies are needed to elucidate the relationship between BCG vaccine, LTBI, and COVID-19 infection.

One and a half years into the COVID-19 pandemic - exit strategies and efficacy of SARS-CoV-2 vaccines for holistic management and achieving global control

One and a half years into the pandemic, SARS-CoV-2 is still here to stay. Whilst rapid several effective COVID-19 vaccines have been developed and are being rolled out, the critical questions remain whether vaccines provide widespread protection against infection and reinfection, and what the duration of protection is. Community wide control cannot be obtained until almost everyone is immune. Vaccine production must be ramped up to cover the world population. The price of herd immunity through natural infection is high mortality in the elderly and morbidity in other age groups including children and Long-COVID. We must expect a new wave in the coming winter. The severity will depend on the proportion of the population with immunity from natural infections or immunisation. Therefore, control rests on a population wide immunisation including children, which may or may not need to be repeated if new SARS-CoV-2 variants evolve that can escape immunity from either previous infections or immunisations. Preventing long term sequelae of COVID-19 also remains a priority.

Treatment of SARS-CoV-2 pneumonia with favipiravir: early results from the Ege University cohort, Turkey

Background/aim: The aim of this descriptive article is to share the experience in Ege University, Turkey with favipiravir in the treatment of severe SARS-CoV-2 pneumonia. Materials and methods: This retrospective descriptive study included patients diagnosed with COVID-19 who presented with or developed severe pneumonia. Results: Forty patients who completed a full course (at least 5 days) of favipiravir were included in the study. At baseline, 30 (75%) patients required treatment for respiratory distress. Thirty-three patients (82.5%) were discharged from the hospital with full recovery, 6 patients (15%) died and 1 case (2.5%) was still at the intensive care unit (ICU) when this paper was written. Conclusion: This study provides relevant information for the treatment of COVID-19, suggesting that favipiravir was associated with significant clinical and laboratory improvements in the majority of the patients, is a safe drug with no serious side effects and would merit further investigation.

[Comparison of Two Anti-HIV Confirmatory Assays: Recombinant HIV 1/2 Line Immunoassay and Geenius HIV 1/2 Confirmatory Test]. / Iki Anti-HIV Dogrulama Testinin Karsilastirilmasi: Rekombinant HIV 1/2 "Line Immunoassay" ve Geenius HIV 1/2 Dogrulama Testi.

The main purpose in the diagnosis of human immunodeficiency virus (HIV) infection is to rapidly and accurately identify people with HIV infection. It is recommended that samples that are repeatedly reactive should be verified/supported according to the classical algorithms of international and national guidelines. The recombinant "line immunoassay test (LIA)", which has been used for many years, is studied with the accumulated samples to be cost and labor-effective. In this study, the supplemental recombinant HIV 1/2 LIA (INNO-LIA®, Fujirebio, Ghent, Belgium) used to confirm and differentiate the diagnosis of HIV-1 and HIV-2 infections, and an immunochromatographic supplemental test (Geenius™ (Bio-Rad Laboratories, Marnes-la-Coquette, France) which can provide faster results were compared. One hundred fifty serum samples sent to Ege University Faculty of Medicine Hospital Medical Virology Laboratory with anti-HIV 1/2 and p24 antigen positive and indeterminant results and three HIV-1 positive external quality control samples were included in the study. Samples were tested both with the Geenius™ HIV 1/2 (Bio-Rad Laboratories, Marnes-la-Coquette, France) and recombinant HIV 1/2 LIA (INNO-LIA®, Fujirebio, Ghent, Belgium). HIV 1 viral load was evaluated by using Abbott real-time HIV-1 test in Abbott m200sp system (Abbott Molecular, Wiesbaden, Germany) in plasma samples. In both assays, the results were consistent in 147 samples (96.08%). Six samples that have discordant results were as follows: one sample was LIA HIV-1 positive and Geenius indeterminate, two samples were LIA indeterminant and Geenius HIV-1 positive, and in three samples, LIA was indeterminate and Geenius negative. In two EIA reactive samples (2/97, 2.06%) and three EIA negative samples (3/53, 5.66%) LIA results were indeterminant. Geenius test, on the other hand, correctly identified HIV positive and negative samples. The immunochromatographic test could be used in the diagnostic algorithm of HIV infection, due to its short application time, not being labor intensive, its ability to distinguish HIV-1/2, its high sensitivity/specificity compared to LIA, and the compliance with LIA. However, it should be noted that in acute HIV infection, all analytical antibody tests, become reactive later than the fourth generation enzyme immunoassays.

SARS-CoV-2 epidemiology and control, different scenarios for Turkey

Background/aim: Coronavirus Infectious Disease 2019 (COVID-19) is now a pandemic spreading in most countries including Turkey. Materials and methods: The current knowledge of COVID-19 and the virus causing it, SARS-CoV-2, was reviewed. The epidemiology and control in different countries was compared and the differences discussed. Results: The population attack rates and case fatality rates vary from country to country with Lombardy in northern Italy reporting an attack rate in the general population of 0.37% compared to 0.004% in Hong Kong. The differences are caused by different testing strategies and reporting systems. Conclusion: Turkey is early in the outbreak. Different control strategies are available with South Korea, Hong Kong and Singapore being models to follow.

[Investigation of human herpesvirus-8 seroprevalence in blood donors and HIV-positive patients admitted to Ege University Medical School Hospital, Turkey]. / Ege Üniversitesi Tip Fakültesi Hastanesine basvuran kan donörlerinde ve HIV-pozitif hastalarda insan herpesvirusu-8 seroprevalansinin arastirilmasi.

Human herpesvirus 8 (HHV-8), classified in Herpesviridae family, is the etiological agent of Kaposi's sarcoma (KS), primary effusion lymphoma and multicentric Castleman's disease. In contrast to the other herpesviruses, HHV-8 seroprevalence is low in general populations; however, the higher prevalence observed in individuals with immunodeficiencies such as AIDS poses an increased risk for KS. The global distribution of HHV-8 shows great variations, with the highest seroprevalence seen in Africa. The number of studies on the seroprevalence of HHV-8 in Turkey are limited. The aim of this study was to determine the HHV-8 seroprevalences in healthy blood donors and HIV-positive patients, that will contribute HHV-8 seroepidemiological data in our country. This study was designed as a cross-sectional study. A total of 551 healthy donors (76 female, 475 male; age range: 18-65 years) admitted to Ege University Medical School Hospital, Blood Center for blood donation between December 2013-January 2014, and 173 HIV-positive patients (30 female, 143 male; age range: 18-65 years) admitted to infectious diseases outpatient clinic between October 2013-January 2014, were included in the study. A commercial ELISA method (KSHV/HHV-8 IgG ELISA Kit, Advanced Biotechnologies Inc, USA) was used for the detection of IgG antibodies that were structured against HHV-8 lytic antigens. In the study, 29 (29/551, 5.3%) of blood donors and 44 (44/173, 25.4%) of HIV-positive patients, with a total of 73 (73/724, 10.1%) cases were found as HHV-8 seropositive. The difference between blood donors and HIV-positive patients in terms of HHV-8 seropositivity rates was statistically significant (5.3% versus 25.4%; p< 0.05). In both of the study groups, no statistically significant difference was detected between HHV-8 seropositivity with gender and age. When considering HIV-positive patients, no statistically significant difference was observed between HHV-8 seropositivity with the duration of anti-HIV positivity, CD4(+) T cell count, HIV-RNA status and history of having sexually transmitted disease. As a result, HHV-8 seroprevalence rate detected in our study is similar to the data of other studies performed in Turkey, as well as the rates reported from other European and Asian countries.

[HIV-1 subtype distribution determined by phylogenetic analysis of pol gene sequences and automated subtyping tools among HIV-1 isolates from the Aegian Region of Turkey]. / Ege Bölgesi'nde izole edilen HIV-1 izolatlarinin alttip dagiliminin pol gen bölgesi filogenetik analizi ve otomatize araçlar kullanilarak belirlenmesi.

Human immunodeficiency virus (HIV) exhibiting remarkable genetic variability, includes two genotypes namely HIV-1 (group M, N, O and P) and HIV-2 (group A-H). HIV-1 group M, which is mainly the cause of the AIDS pandemic, is divided into nine pure subtypes, more than 45 circulating recombinant forms (CRF) and numerous unique recombinant forms (URF). According to the documents of Turkish Government of Health, among a total of 6802 HIV-positive cases, 1096 of them were defined as AIDS as of June 2013 in Turkey. Although subtype B is the predominant subtype, recent studies indicate higher proportion of CRFs similar to their increasing role in the HIV pandemic. The aim of this study was to determine the subtype distribution of HIV-1 strains isolated from 70 patients (61 male, 9 female; age range: 16-73 yrs, mean age: 39.6 yrs) who presented to our institution between April 2008-June 2013. HIV-1 strains were subtyped by phylogenetic analysis of the pol gene region and commonly used automated subtyping tools namely, Stanford HIV db v6.2.0 and Rega v3.0. Pol sequences retrieved from the Los Alamos database and from GeneBank, were trimmed from full-length genomes. Phylogenetic analysis of the 1302 base pair of the pol gene region was performed using Mega v5.2 software. The sequences were aligned using Muscle and phylogenetic distances between sequences were estimated by using Kimura two-parameter model (transition/transversion ratio: 2.0). Tree topology was obtained using neighbour-joining method and bootstrap value was set at 1000. Sixty-one (87.1%) patients were antiretroviral treatment (ART)-naive and nine were on different ART regimens. The subtypes of the isolates according to phylogenetic analysis were found as follows; 31 (44.2%) subtype B, 24 (34.2%) CRF42_BF, 6 (8.5%) B/CRF02_AG recombinants, 5 (7.1%) sub-subtype A1, 1 (1.4%) sub-subtype F1, 1 (%1.4) CRF 25_cpx, 1 (1.4%) CRF02_AG and 1 (1.4%) CRF01_AE. Rega v3.0 subtyping tool produced five discrepant results (4 B/CRF02-AG and 1 CRF42_BF) compared to phylogenetic analysis. Stanford HIVdb v6.2.0 had eight results (3 CRF42_BF, 2 subtype B, 2 sub-subtype A1, 1 CRF25_cpx) that were not concordant with phylogenetic analysis. Stanford HIVdb v6.2.0 was able to subtype all B/CRF02_AG recombinant strains. B/CRF02_AG recombinants which were seen among homosexual men in France were for the first time isolated in Turkey from five men (2 homosexual, 2 bisexual, 1 heterosexual) and one heterosexual woman. CRF42_BF had not been found in Turkey previously and it has not been a common type isolated in neighboring countries either. Full genome sequencing could be helpful to further analysis of those isolates. Our results support the latest studies from Turkey reporting increase in the proportion of CRF-related infections. This is not an unusual finding when geographical location of Turkey is considered. Nevertheless, more comprehensive data regarding molecular epidemiology and subtype distribution of HIV-1 isolates in Turkey are needed.

Missed Opportunities in HIV Testing in Turkiye: Implications for Late Diagnoses.

BACKGROUND: Late diagnosis of HIV infection is a major global problem. In Turkiye, only 41%-50% of people living with HIV are diagnosed, suggesting that many opportunities for HIV testing might be missed. SETTING: The aim of this study was to determine the missed testing opportunities for HIV in healthcare settings in Turkiye and the predictors for missed opportunities (MOs). METHODS: The study included patients with a new HIV diagnosis, presenting to care between January 2018 and December 2020. They were given a verbal questionnaire face to face, by a telephone call or an online meeting for visits to a health care setting within the year before their diagnosis. Electronic medical records were also examined. RESULTS: The sample included 198 patients with at least 1 visit to any health care setting, with a total of 1677 visits. Patients had an indication for HIV testing in 51.3% (861/1677) of the visits; an HIV test was not offered in 77.9% (671/861) and was considered a MO. The highest number of MOs was in emergency departments (59.8%) (180/301). The most common reason for visiting was constitutional symptoms and indicator conditions (55.4%) (929/1677). University graduates and those with a CD4+ T-cell count <200/mm 3 were more likely to have a MO. CONCLUSIONS: Many opportunities to diagnose HIV at an early stage are missed in health care settings in Turkiye. Considering the rapidly increasing number of new diagnoses in the last decade, urgent action needs to be taken.

[Role of line immunoassay in the diagnosis of early HIV infection: a diagnostic case]. / Erken dönem HIV enfeksiyonunda "line immunoassay" testinin yeri: Tanisal bir olgu.

Combined p24 antigen-HIV antibody fourth-generation assays that identify most of the early HIV infections have been used extensively worldwide for several years. This poses challenges for the traditional algorithm of line immunoassay (LIA) confirmation. LIA tests are useful methods with their high specificity and their ability to differentiate HIV-1 from HIV-2, but they are reactive days after the fourth generation enzyme immunoassays. With acute HIV infection, high levels of infectious virus are detectable in serum and genital secretions. The rate of transmission during acute HIV infection is higher than the established HIV infection, for this reason, new HIV testing strategies need to focus on sensitivity, especially for this highly contagious phase immediately after infection. Serum sample of a patient sent to Ege University Hospital Clinical Virology Laboratory was repeatedly reactive with low signal/cutoff ratios with two different commercial fourth generation enzyme immunoassays (Architect HIV Ag/Ab Combo Reagent Kit, Abbott, Germany and Vidas HIV Duo Quick, Biomerieux, France). The sample was non-reactive with the LIA (INNO-LIA HIV I/II Score, Innogenetics, Belgium) and HIV RNA (RealTime HIV-I Amplification Reagent Kit, Abbott, USA) result was positive (4.1 x 10(5) copies/ml). With the presentation of this case, the role of LIA in the diagnosis of early HIV infection and its place in test algorithms were questioned.

Kidney Transplant in a Human Immunodeficiency Virus-Positive Patient: Case Report of Drug Interactions.

End-stage renal disease in the human immunodeficiency virus-positive population is increasing. Kidney transplant is the optimal therapy for this population rather than dialysis modalities if some criteria are met. These include undetectable plasma human immunodeficiency virus RNA, CD4 cell count over 200 cells/µL, and the absence of any AIDS-defining illness. Here, we describe the first living-donor kidney transplant in a human immunodeficiency virus-positive recipient in Turkey. The patient, a 52-year-old male diagnosed as human immunodeficiency virus positive, was on antiretroviral therapy, which consisted of 400 mg twice daily darunavir, 100 mg/day ritonavir, and 50 mg/day dolutegravir. He had been negative for human immunodeficiency virus RNA for the past 3 years. The patient developed renal insufficiency without any known cause and started hemodialysis. A living donor transplant from his son was performed, and the patient received ATG Fresenius-S (Neovii Biotech, Rapperswil, Switzerland) induction and a maintenance immunosuppression therapy consisting of methyl-prednisolone, mycophenolate mofetil, and tacrolimus. There were no incidences of delayed graft function or acute rejection. Because of tacrolimus and ritonavir interaction, tacrolimus trough levels were too high. With tacrolimus withdrawn, tacrolimus trough level decreased to detectable levels 2 weeks later. Antiretroviral therapy was continued on the same dosage. At month 4 posttransplant, the patient's creatinine level was 1.01 mg/dL. At present, the patient has had no complications and no episodes of rejection. Kidney transplant is the most favorable replacement therapy for HIV-positive patients who are under controlled AIDS care with highly active antiretroviral therapy. However, drug interactions should be carefully evaluated.