Georgios K. Nikolopoulos

Impact of Hepatitis B Virus Infection on the Progression of AIDS and Mortality in HIV-Infected Individuals: A Cohort Study and Meta-Analysis

BACKGROUND The effect of hepatitis B virus (HBV) infection on the natural history of human immunodeficiency virus (HIV) disease remains uncertain. Therefore, a retrospective cohort study was conducted to examine the influence of HIV-HBV coinfection on AIDS development and overall mortality. Moreover, our results were added to those of previous studies in a literature-based meta-analysis. METHODS Serum samples obtained from HIV-seropositive patients from 1984 through 2003 were retrospectively tested for hepatitis B surface antigen. Multivariable analyses were performed using Poisson and logistic regression models. For meta-analytic purposes, eligible articles were identified and relevant data were abstracted. Pooled estimates of effect were calculated applying fixed and random effects models. RESULTS The prevalence of chronic HBV infection (documented hepatitis B surface antigen seropositivity for >6 months) among 1729 HIV-positive patients was approximately 6%. The multivariable analyses in our primary study revealed no significant impact of concomitant HIV-HBV infection on progression to AIDS and all-cause mortality. However, a meta-analysis performed on data from 12,382 patients enrolled in 11 studies revealed a significant effect of HIV-HBV coinfection on overall mortality (pooled effect estimate, 1.36; 95% confidence interval, 1.12-1.64). The increased rate of death among coinfected individuals was observed in the meta-analyses of studies conducted both before (pooled effect estimate, 1.60; 95% confidence interval, 1.07-2.39) and after (pooled effect estimate, 1.28; 95% confidence interval, 1.03-1.60) commencement of highly active antiretroviral therapy. CONCLUSIONS HIV-HBV coinfection seems to affect all-cause mortality, and strategies to reduce liver damage in patients coinfected with HIV and HBV are justified.

Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4178 cases and 4590 controls

AIM We conducted a systematic review and a meta-analysis, in order to investigate the potential association of cytokine gene polymorphisms with either aggressive or chronic periodontal disease. MATERIAL AND METHODS A comprehensive literature search was performed. We retrieved a total of 53 studies summarizing information about 4178 cases and 4590 controls. Six polymorphisms were included in our meta-analysis which are the following: IL-1A G[4845]T, IL-1A C[-889]T, IL-1B C[3953/4]T, IL-1B T[-511]C, IL-6 G[-174]C and TNFA G[-308]A. Random effect methods were used for the analysis. We calculated the specific odds ratios along with their 95% confidence intervals to compare the distribution of alleles and genotypes between cases and controls. RESULTS AND CONCLUSIONS Using random effect methods we found statistically significant association of IL-1A C[-889]T and IL-1B C[3953/4]T polymorphisms with chronic periodontal disease without any evidence of publication bias or significant statistical heterogeneity. A weak positive association was also found concerning IL-1B T[-511]C and chronic periodontal disease. No association was found for all the cytokines examined as far as the aggressive form of the disease is concerned. Future studies may contribute to the investigation of the potential multigenetic predisposition of the disease and reinforce our findings.

Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and venous thrombosis - A meta-analysis

The effect of the 675 insertion/deletion (4G/5G) polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene on the risk of venous thromboembolism (VTE) remains controversial. In this study, we performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out up until September 2006. A total of 22 articles were included in the analysis that was performed using random effects models. Eighteen papers, concerning patients without another known risk factor, comprised 2,644 cases and 3,739 controls. The alleles contrast (4G vs. 5G allele) yielded a statistically significant odds ratio (OR) of 1.153 (95% confidence interval [CI]: 1.068-1.246). In a sub-analysis of five studies that included 256 cases with another genetic risk factor and 147 controls, the combined per-allele OR was still significant (OR: 1.833,95% CI: 1.325-2.536). On the contrary, the analysis of five studies regarding cases with a non-genetic risk factor for VTE (antiphospholipid antibody syndrome, Behcet disease) provided insignificant results in all aspects. There was no evidence for heterogeneity and publication bias in all analyses. Based on our findings, the 4G allele appears to increase the risk of venous thrombosis, particularly in subjects with other genetic thrombophilic defects. Recommendation for detection of this polymorphism in evaluating thrombophilia in such patients might be considered.

Economic Recession and Emergence of an HIV-1 Outbreak among Drug Injectors in Athens Metropolitan Area: A Longitudinal Study

Background During 2011, a dramatic increase (1600%) of reported HIV-1 infections among injecting drug users (IDUs) was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak. Methods Our study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP) of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008–2012). Results IDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5%) during 1998–2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all p<0.001). The slope of anti-HCV prevalence in the sentinel populations of IDUs and in “new” drug injectors was found 120 and 1.9-fold (p = 0.007, p = 0.08 respectively) higher in 2008–2012 (economic recession) compared with 2002–2006. The median (25th, 75th) size of transmission networks were 34 (12, 58) and 2 (2, 2) (p = 0.057) in 2008–2012 and 1998–2007, respectively. The coverage of harm reduction services was low throughout the study period. Conclusions Scaling-up harm reduction services and addressing social and structural factors related to the current economic crisis should be urgently considered in environments where HIV-1 outbreaks may occur.

Increasing Prevalence of HIV-1 Subtype A in Greece: Estimating Epidemic History and Origin

BACKGROUND In North America and Europe, human immunodeficiency virus (HIV)-1 infection has typically been dominated by subtype B transmission. More recently, however, non-B subtypes have been increasingly reported in Europe. METHODS We analyzed 1158 HIV-1-infected individuals in Greece by DNA sequencing and phylogenetic analyses of protease and partial reverse-transcriptase regions. RESULTS We found that the prevalence of non-B subtypes has increased over time and that this significant trend can be mainly attributed to subtype A, which eventually surpassed subtype B in prevalence in 2004 (42% and 33%, respectively). Multivariate analysis revealed that the year of HIV diagnosis was independently associated with subtype A infection (odds ratio for being infected with subtype A for a 10-year increase in the time period of diagnosis, 2.09 [95% confidence interval, 1.36-3.24]; P<.001). Phylogenetic analysis revealed that the subtype A epidemic in Greece is the result of a single founder event. The date of the most recent common ancestor of the subtype A in Greece was estimated to be 1977.9 (95% highest posterior density interval, 1973.7-1981.9). CONCLUSIONS Subtype A circulates among the long-term residents of Greece. This is in contrast to the situation in most European countries, in which infection with non-B genetic forms is associated either with being an immigrant or heterosexual or with intravenous drug use.

The GNB3 C825T polymorphism and essential hypertension: a meta-analysis of 34 studies including 14,094 cases and 17,760 controls.

Objectives The C825T single nucleotide polymorphism of the G-protein β3 (GNB3) has been implicated in susceptibility to essential hypertension, through the expression of an alternatively spliced truncated variant. In an effort to clarify earlier inconclusive results, we performed a meta-analysis of population-based case–control genetic association studies. Methods Random-effects methods were applied on summary data in order to combine the results of the individual studies. Results We identified in total 34 studies, including 14 094 hypertensive cases and 17 760 controls. The TT versus CC + CT contrast yielded an overall odds ratio (OR) of 1.08 [95% confidence interval (CI): 1.01, 1.15], the contrast of TT + CT versus CC, an OR of 1.17 (95% CI: 1.06, 1.29), whereas that of the T allele versus C allele yielded a non-significant OR of 1.05 (95% CI: 0.98, 1.13). There was moderate evidence for a publication bias in the latter two contrasts, which was eliminated after excluding studies not in Hardy–Weinberg equilibrium and those performed on non-normal populations (those with a diagnosis of diabetes, obesity and myocardial infarction). Subgroup analyses revealed that non-significant estimates arose from studies on Asian populations, as opposed to the Caucasian ones. Furthermore, the frequency of the T allele was lower in Caucasians and these populations were found to inhabit higher latitudes. Conclusions The findings are in agreement with a recently proposed causal model for systolic blood pressure, which correlates it with the T allele and the absolute latitude. Further studies are needed in order to fully address questions about the aetiological mechanism of the particular association, as well as to study the effect in populations of African descent.

A Method for Meta-Analysis of Case-Control Genetic Association Studies Using Logistic Regression

We propose here a simple and robust approach for meta-analysis of molecular association studies. Making use of the binary structure of the data, and by treating the genotypes as independent variables in a logistic regression, we apply a simple and commonly used methodology that performs satisfactorily, being at the same time very flexible. We present simple tests for detecting heterogeneity and we describe a random effects extension of the method in order to allow for between studies heterogeneity. We derive also simple tests for assessing the most plausible genetic model of inheritance, and its between-studies heterogeneity as well as adjusting for covariates. The methodology introduced here is easily extended in cases with polytomous or continuous outcomes as well as in cases with more than two alleles. We apply the methodology in several published meta-analyses of genetic association studies with very encouraging results. The main advantages of the proposed methodology is its flexibility and the ease of use, while at the same time covers almost every aspect of a meta-analysis providing overall estimates without the need of multiple comparisons. We anticipate that this simple method would be used in the future in meta-analyses of genetic association studies. A STATA command performing all the available computations is available at http://bioinformatics.biol.uoa.gr/~pbagos/metagen/.

Homelessness and Other Risk Factors for HIV Infection in the Current Outbreak Among Injection Drug Users in Athens, Greece

Objectives. We examined HIV prevalence and risk factors among injection drug users (IDUs) in Athens, Greece, during an HIV outbreak. Methods. We used respondent-driven sampling (RDS) to recruit 1404 IDUs to the Aristotle intervention in August to October 2012. We interviewed participants and tested for HIV. We performed bivariate and multivariate analyses. Results. Estimated HIV prevalence was 19.8% (RDS-weighted prevalence = 14.8%). Odds of infection were 2.3 times as high in homeless as in housed IDUs and 2.1 times as high among IDUs who injected at least once per day as among less frequent injectors (both, P < .001). Six percent of men and 23.5% of women reported transactional sex in the past 12 months, and condom use was low. Intercourse with non-IDUs was common (53.2% of men, 25.6% of women). Among IDUs who had been injecting for 2 years or less the estimated incidence rate was 23.4 new HIV cases per 100 person-years at risk. Conclusions. Efforts to reduce HIV transmission should address homelessness as well as scaling up prevention services, such as needle and syringe distribution and other risk reduction interventions.

Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of ischemic stroke : a meta-analysis

This study investigated the hypothesis that the insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor type-1 gene affects the risk for ischemic stroke, since results concerning this association have been controversial. We therefore performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out until January 2006. The analysis was performed using random-effects models and meta-regression. Eighteen eligible studies were retrieved (15 case–control studies and three cohort studies). The case–control studies included 3104 cases and 4870 control individuals concerning the contrast of 4G/4G versus remaining genotypes. The 4G pooled allele frequencies in cases and controls were 54.21 and 54.75%, respectively. Overall, the per-allele odds ratio of the 4G allele was 0.98 (95% confidence interval, 0.858–1.121). Regarding genotypes, we derived nonsignificant odds ratios in all contrasts. The subanalysis including the three studies with a prospective design in the 4G/4G versus 5G/5G contrast derived a significant result (relative risk, 0.523; 95% confidence interval, 0.353–0.775), but the estimated effect size was insignificant when cohort and case–control studies were analyzed together (relative risk, 0.848; 95% confidence interval, 0.662–1.087). We failed to demonstrate a significant association between the 4G/5G polymorphism and ischemic stroke under basal conditions. Determination of plasminogen activator inhibitor type-1 function seems of much higher clinical value than determination of the 4G/5G polymorphism. The effect of this genotype on risk of ischemic stroke in acute stressful diseases and the role of cohort studies in genetic epidemiology, however, warrant further investigation.

Fcγ receptor polymorphisms and their association with periodontal disease: a meta-analysis

AIM A systematic review and a meta-analysis were conducted in order to investigate the potential association of Fcgamma receptor (FcgammaR) polymorphisms with susceptibility to aggressive and chronic periodontal disease. MATERIALS AND METHODS A database search yielded a total of 17 studies involving 1685 cases and 1570 controls. Three polymorphisms were included in the meta-analysis: FcgammaRIIA H131R (rs1801274), FcgammaRIIIA F158V (rs396991) and FcgammaRIIIB NA1/NA2. Random-effect models were used in the analysis. Odds ratios (ORs) along with their 95% confidence intervals (CIs) were computed to compare the distribution of alleles and genotypes between cases and controls. RESULTS AND CONCLUSIONS The FcgammaRIIIB NA1/NA2 polymorphism was associated with both aggressive (per-allele OR 2.005, 95% CI: 1.044, 3.851) and chronic periodontitis (recessive contrast NA2NA2 versus NA1NA1+NA1NA2 OR 1.397, 95% CI: 1.039, 1.878). The analysis showed weak evidence for association between the FcgammaRIIA H131R polymorphism and aggressive periodontitis in Asians (R versus H allele OR 1.579, 95% CI: 1.025, 2.432). On the contrary, no relationship was identified between FcgammaRIIIA F158V and periodontal disease. Accumulating evidence from basic research makes the suggested association between FcgammaRIIIB NA1/NA2 polymorphism and periodontitis biologically plausible. Further research, however, is needed in order to assess possible gene-gene or gene-environment interactions (i.e. with smoking).