Olga Tsachouridou

Molecular and epidemiological characterization of HIV-1 infection networks involving transmitted drug resistance mutations in Northern Greece

OBJECTIVES To determine the contribution of transmission clusters to transmitted drug resistance (TDR) in newly diagnosed antiretroviral-naive HIV-1-infected patients in Northern Greece during 2000-07. METHODS The prevalence of TDR was estimated in 369 individuals who were diagnosed with HIV-1 infection in the period 2000-07 at the National AIDS Reference Laboratory of Northern Greece. Phylogenetic analysis was performed using a maximum likelihood method on partial pol sequences. TDR was defined in accordance with the surveillance drug resistance mutation list (2009 update). RESULTS The overall prevalence of TDR in our population was 12.5% [46/369, 95% confidence interval (CI) 9.1%-15.8%], comprising 7.6% (28/369) resistant to nucleoside reverse transcriptase inhibitors, 5.4% (20/369) resistant to non-nucleoside reverse transcriptase inhibitors and 3.3% (12/369) resistant to protease inhibitors. Dual class resistance was identified in 3.8% (14/369). Infection with subtype A was the sole predictor associated with TDR in multivariate analysis (odds ratio 2.15, 95% CI 1.10-4.19, P = 0.025). Phylogenetic analyses revealed three statistically robust transmission clusters involving drug-resistant strains, including one cluster of 12 patients, 10 of whom were infected with a strain carrying both T215 revertants and Y181C mutations. CONCLUSIONS Our findings underline the substantial impact of transmission networks on TDR in our population.

Older HIV-infected patients--an underestimated population in northern Greece: epidemiology, risk of disease progression and death.

OBJECTIVES HIV prevalence among older people is on the increase. The aim of this study was to evaluate the epidemiological and clinical features at diagnosis and survival of older patients. METHODS This was a retrospective analysis of the data of 558 newly diagnosed antiretroviral-naïve patients between January 1998 and December 2008. Patients were divided into two groups according to their age at diagnosis: ≥50 years (n=103) and 18-49 years (n=455). RESULTS The most common risk factor for older patients was heterosexual contact (p<0.013). Older patients were more likely to suffer from hypertension (33.0% vs. 5.1%, p<0.0005), cardiovascular disease (20.4% vs. 2.9%, p<0.0005), neurological disorders (11.7% vs. 5.5%, p=0.02), renal dysfunction (12.6% vs. 5.3%, p=0.01), and infections (66.0% vs. 49.7%, p=0.003) than their younger counterparts, and to have more hospital admissions during follow-up (47.5% vs. 19.6%, p<0.0005). Older patients had a shorter survival time (p<0.0005). A statistically significant increase in CD4+ cell number through time was observed in both groups (p<0.0005). Younger patients reached higher magnitudes of absolute numbers of CD4+ cells during follow-up (p<0.0005) after the initiation of antiretroviral therapy. The total number of patients with clinical AIDS from baseline throughout the study period was also higher in the older age group (35.9% vs. 25.0%). CONCLUSIONS HIV-infected people aged ≥50 years differ in epidemiological and clinical features to younger HIV-infected people. The issue of increasing prevalence of HIV infection is a matter of concern due to existing comorbidities, which probably lead to higher mortality rates and faster progression to clinical AIDS.

Time trends and correlates of late presentation for HIV care in Northern Greece during the decade 2000 to 2010

The aim of our study was to assess the extent of late presentation for HIV care in Northern Greece during the period 2000 to 2010 and to explore correlations aiming to provide guidance for future interventions.

High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece, data from 2009–2011

We conducted a retrospective study on the prevalence and correlates of transmitted drug resistance among newly-diagnosed antiretroviral naive human immunodeficiency virus (HIV) patients in Northern Greece, during the period 2009-11. Transmitted drug resistance was documented in 21.8% of patients enrolled, affecting approximately 40% of subtype A HIV-1-infected individuals. Overcoming challenges due to the ongoing financial crisis, effective preventive measures should be implemented to control further dissemination of resistant HIV strains.

The controversial impact of B cells subsets on immune response to pneumococcal vaccine in HIV-1 patients.

BACKGROUND Chronic HIV infection leads to severe perturbations of the B cell populations and hypo-responsiveness to vaccines. The associations between circulating B cell subpopulations and the antibody response to pneumococcal polysaccharide vaccine in antiretroviral-naïve and treated patients were studied. METHODS Sixty-six HIV-infected adults were grouped according to antiretroviral therapy (ART) and CD4+ cell count; 31 were ART-naïve and 35 were ART-treated, and they were matched for age, CD4 cell count, and duration of HIV infection. All subjects were immunized with the 23-valent polysaccharide vaccine against Streptococcus pneumoniae. Pre- and post-vaccination B cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and at 4 and 48 weeks post-vaccination. RESULTS Patients under highly active antiretroviral therapy (HAART) had significantly higher antibody levels against pneumococcal vaccine antigens, while an adequate number of patients responded to vaccination. Memory B cells were diminished over time, although treated patients maintained higher levels of all subsets studied, with the exception of activated memory and isotype-switched memory B cells. CONCLUSIONS Low concentrations of total B cells and exhausted memory B cells was the strongest independent predictor of poor pneumococcal vaccine responsiveness, emphasizing that B cell subset disturbances are associated with a poor vaccine response among HIV-infected patients.

Deficient Phagocytosis Among HIV-1 Infected Adults Over Time Even in HAART Setting

BACKGROUND Phagocytosis is regarded to be impaired in HIV-1 infected adults, leading to high frequency and severity of several infections in this population. Data is contradictory with regards to individual facets in HIV infection. OBJECTIVE Aim of this study was to assess the phagocytic activity during the natural course of HIV infection. METHOD It is a longitudinal study assessing natural course and impairment of neutrophil and monocyte phagocytosis in both naïve and HAART treated patients. RESULTS A lower neutrophil phagocytic activity was recorded in naïve patients compared to treated patients. Interestingly, a downward trend of neutrophil phagocytic activity was recorded in both groups, irrespectively of HAART intake, within 48 weeks of observation. CONCLUSION Defects of innate immunity appear to be present in HIV infected patients regarding phagocytic activity of monocytes and of neutrophils which seems to decline over time. These deficiencies are influenced by the levels of CD4 cell counts and viral load.

Prolonged and high dosage of tigecycline – successful treatment of spondylodiscitis caused by multidrug-resistant Acinetobacter baumannii : a case report

BackgroundThe incidence of infectious spondylodiscitis has been increasing over the last few years. This reflects the expanding elderly and immunocompromised populations and the rising implementation of invasive spinal procedures. Infection may be inoculated into the disc space directly during invasive spinal procedures. Osteomyelitis caused by Acinetobacter species is rare and mainly caused by multidrug-resistant strains.Case presentationWe present the case of a 72-year-old Greek woman with postoperative spondylodiscitis caused by a multidrug-resistant Acinetobacter baumannii strain that was successfully treated, after she declined surgical treatment, with prolonged and high dosage of tigecycline. She received intravenously administered tigecycline 200 mg per day for 60 days and then 100 mg per day for a total of 102 days and was infection-free.ConclusionsWe reviewed the literature on the role of Acinetobacter baumannii as a cause of osteomyelitis, emphasizing the difficulty of treatment and the potential role of tigecycline in conservative treatment of the infection. We believe that 102 days in total is the longest time that any patient has received tigecycline in the literature, thus our patient is a unique case of successful treatment of spondylodiscitis.

West Nile Virus Seroprevalence and Behavioral Risks in HIV-1 Infected Individuals, Northern Greece, 2011

OBJECTIVES This study sought to assess the West Nile Virus (WNV) seroprevalence and behavioral risk factors for WNV infection in HIV-1 infected individuals in Northern Greece in 2011. METHODS We prospectively enrolled 91 HIV-1 consecutive patients followed up in the HIV clinic of the AHEPA University Hospital in the period from November to December 2011. Serum samples were tested for the presence of WNV IgG antibodies. All subjects were administered a standardized questionnaire to evaluate for risk factors for WNV infection. RESULTS WNV IgG antibodies were detected in three subjects (3.3%, 95% CI 0.7-9.3%), two of whom were of African origin. The prevalence of WNV antibodies in HIV patients of Greek origin was 1.2% (95% CI: 0.03% - 6.3%). In the sample surveyed, 53.6% (95% CI: 42.4% to 64.5%) were aware of WNV prevention measures; 2.2% reported no implementation of prevention measures, whereas 46.1% implemented at least three measures. Approximately one half of the patients reported outdoor activities for more than two hours from dusk to dawn. None of the IgG-positive patients reported any symptoms compatible with WNV disease during the season at risk. CONCLUSIONS Among native Greek HIV patients, the WNV seroprevalence is 1.2%. A considerable proportion of patients was aware of WNV prevention measures and implemented some of these. HIV patients and other categories of immunocompromised patients are at increased risk of neuroinvasive disease, and widespread implementation of prevention measures should be strongly encouraged in this patient population.

Prevalence and correlates of persistent intracellular HIV transcription in individuals on efavirenz versus atazanavir-based regimens: A prospective cohort study

Objectives Despite successful virological suppression, HIV transcription frequently persists intracellularly. In this study, we hypothesize that HIV persistent transcription(HIVpt) may affect to a different extent patients on stable efavirenz(EFV) versus atazanavir(ATV)-based regimens. The role of the expression of drug efflux transporters in HIVpt was also investigated. Methods We prospectively enrolled 51 virologically suppressed patients on first-line treatment for one year with EFV or ATV combined with emtricitabine and tenofovir and followed them up for one year. Simultaneous ultrasensitive subpopulation staining/hybridization in situ(SUSHI) was performed to identify HIVpt in CD4+ T-cells and in the CD4+CD45RO+ T-cell subpopulation. The differential mRNA expression of P-glycoprotein(P-gp/ABCB1) and multidrug resistance-associated protein-1(MRP1/ABCC1) was also evaluated. Univariate logistic regression models were used to evaluate predictors of HIVpt. Results In the CD4+ T-cell population, HIVpt affected 13/30 of patients on EFV versus 10/21 on ATV. In the CD4+CD45RO+ T-cell population, HIVpt was present in 14/30 of patients on EFV versus 15/21 on ATV. A trend for association was observed between the risk of HIVpt and ATV treatment in the CD4+CD45RO+ T-cell population (OR 2.86, 95% CI 0.87–9.37, p = 0.083). HIVpt status was not associated with loss of virological suppression or CD4 evolution. We found no evidence of differential expression of the drug efflux transporters P-gp and MRP1. Conclusions Further study is required to evaluate whether the HIVpt profile in specific cell populations may differ across different antiretroviral regimens and to elucidate the potential clinical impact.

Factors associated with poor adherence to vaccination against hepatitis viruses, streptococcus pneumoniae and seasonal influenza in HIV-infected adults

ABSTRACT Introduction: Vaccination against various pathogens is recommended for HIV positive adults. There are not sufficient data either on vaccination coverage of HIV positive adults or the risk factors associated with poor adherence to routine vaccination. Patients-Methods: During the period 2004–2014 vaccination coverage of a group of HIV infected adults against hepatitis A virus (HAV), hepatitis B virus (HBV), seasonal influenza virus and pneumococcal disease was recorded. Vaccination coverage was separated into two chronological periods, before and after 2010, as 2010 marks the start of the economic crisis in Greece. Results: 1210 patients were included in our study. Vaccine coverage throughout the study for hepatitis B, hepatitis A, seasonal influenza and pneumococcal infection was 73.6%, 70.4%, 39% and 79%, respectively. The complete lack of insurance coverage was an independent factor of non-compliance in all proposed vaccines (vaccination against pneumococcal disease: OR: 0.82 95%CI: 0.49–1.35, vaccination against HBV: OR: 0.82, 95% CI: 0.45–1.49, vaccination against HAV OR: 0.54, 95%CI: 0.34–0.87, vaccination against influenza: OR: 1.27, 95% CI: 0.76–2.10). In addition, low educational level was associated with poor compliance to vaccination against pneumococcal disease, hepatitis A, hepatitis B, and influenza. Finally, the recommendation for vaccination after the onset of the economic crisis (2010) led to poor compliance to vaccination against HBV, HAV and pneumococcal disease, but not against influenza. Conclusions: In our study, vaccination coverage for vaccine-preventable diseases was found to be insufficient for HIV positive adults in Northern Greece. Also, low educational level, lack of insurance coverage and economic distress have contributed to poor vaccine compliance, leading to poor protection of the HIV positive population and decreased immune coverage in the community.