HIV-1 RNA can be found at higher levels in cerebrospinal fluid (CSF) than in plasma, termed CSF/plasma discordance. The clinical significance of CSF/plasma discordance is not known and the degree of discordance considered important... more
HIV-1 RNA can be found at higher levels in cerebrospinal fluid (CSF) than in plasma, termed CSF/plasma discordance. The clinical significance of CSF/plasma discordance is not known and the degree of discordance considered important varies. We aimed to determine whether a panel of CSF cytokines, chemokines and associated mediators were raised in patients with CSF/plasma discordance at different levels. A nested case-control study of 40 CSF samples from the PARTITION study. We used a cytometric bead array to measure CSF mediator concentrations in 19 discordant and 21 non-discordant samples matched for plasma HIV-1 RNA. Discordant samples were subdivided into 'high discordance' (>1log10) and 'low discordance' (0.5-1log10, or ultrasensitive discordance). CSF mediators significant in univariate analysis went forward to two-way unsupervised hierarchical clustering based on the patterns of relative mediator concentrations. In univariate analysis 19 of 21 CSF mediators we...
Research Interests: Immunology and Cytokine
Outcomes of chronic infection with hepatitis B virus (HBV) are varied, with increased morbidity reported in the context of HIV coinfection. The factors driving different outcomes are not well understood, but there is increasing interest... more
Outcomes of chronic infection with hepatitis B virus (HBV) are varied, with increased morbidity reported in the context of HIV coinfection. The factors driving different outcomes are not well understood, but there is increasing interest in an HLA Class I effect. We therefore studied the influence of HLA class I on HBV in an African HIV-positive cohort. We demonstrated that virologic markers of HBV disease activity (HBeAg status / HBV DNA level) are associated with HLA-A genotype. This finding supports the role of the CD8+ T cell response in HBV control, and potentially informs future therapeutic T cell vaccine strategies.
Research Interests:
Research Interests:
Whether ART regimens differ in their propensity to allow persistent HIV-1 detection remains unclear. To investigate this, we performed a cross-sectional study to characterize HIV-1 persistence in peripheral blood during suppressive... more
Whether ART regimens differ in their propensity to allow persistent HIV-1 detection remains unclear. To investigate this, we performed a cross-sectional study to characterize HIV-1 persistence in peripheral blood during suppressive therapy with NRTIs plus a PI or nevirapine. Residual plasma HIV-1 RNA was quantified by real-time PCR. Cell-associated proviral total HIV-1 DNA, unspliced and multiply spliced HIV-1 RNA and 2-long terminal repeat (2-LTR) circles were quantified by digital PCR. Comparing PI with nevirapine recipients, residual plasma HIV-1 RNA detection rates were 47/80 (58.8%) versus 37/81 (45.7%), with median (IQR) levels of 4 (3-8) versus 4 (3-7) copies/mL (P = 0.207); detection was less likely with longer duration of suppressive ART (P = 0.020), independently of treatment. HIV-1 DNA was detected in all patients, with median levels of 2.3 (IQR 2.0-2.7) versus 2.5 (IQR 2.1-2.7) log10 copies/10(6) PBMCs, respectively; HIV-1 DNA levels were associated with pre-ART viral load (P = 0.004) and with residual HIV-1 RNA (P = 0.034), unspliced HIV-1 RNA (P = 0.001) and 2-LTR circles (P = 0.005), independently of treatment. No significant differences were revealed in levels of residual plasma HIV-1 RNA, total HIV-1 DNA or intracellular markers of ongoing virus replication (unspliced and multiply spliced HIV-1 RNA and 2-LTR circles) between treatment groups.
Research Interests:
HCV seroprevalence rates in excess of 5% have been recently reported in some HIV cohorts in sub-Saharan Africa (SSA), suggesting an alarming disease burden for which there are no defined screening and management policies. The surveys have... more
HCV seroprevalence rates in excess of 5% have been recently reported in some HIV cohorts in sub-Saharan Africa (SSA), suggesting an alarming disease burden for which there are no defined screening and management policies. The surveys have commonly employed EIA-based antibody assays for screening and rarely tested for HCV RNA to confirm a current infection.
HIV coinfection with HCV has been poorly studied in sub-Saharan Africa, and the reliability of available seroprevalence estimates remains uncertain. The study aim was to determine HCV RNA prevalence in HIV-infected subjects receiving care... more
HIV coinfection with HCV has been poorly studied in sub-Saharan Africa, and the reliability of available seroprevalence estimates remains uncertain. The study aim was to determine HCV RNA prevalence in HIV-infected subjects receiving care in Kumasi, Ghana, and relate the findings to HCV antibody detection. From a population of 1520 HIV-infected adults, all HBsAg-positive subjects (n = 236) and a random subset of HBsAg-negative subject (n = 172) were screened for HCV RNA using pooled plasma; positive samples were genotyped by core and NS5B sequencing. HCV antibodies were detected by three commercial screening assays and confirmed by the line immunoassay. HCV RNA was detected in 4/408 subjects (1.0%, 95% confidence interval 0.0-1.9%), comprising 3/236 (1.3%; 0.0-2.8%) HBsAg-positive and 1/172 (0.6%; 0.0-1.8%) HBsAg-negative subjects. HCV RNA-positive subjects showed reactivity in all three antibody screening assays. Among HCV RNA-negative subjects, 5/67 (7.5%), 5/67 (7.5%) and 19/67 (28.4%) showed antibody reactivity by each screening assay, respectively, including two (3.0%) with reactivity by all three assays. Only one sample (1.5%) had confirmed antibody reactivity by line immunoassay indicating past HCV infection. HCV-positive subjects (three males, two females) were aged 30-46 years, by questionnaire-based interview reported surgical procedures and blood transfusion as risk factors for infection. HCV genotypes were 2 (subtypes 2j, 2l, 2k/unassigned) and 1 (subtype unassigned). Without further testing, HCV antibody screening assays variably overestimated HCV prevalence among HIV-infected subjects in Ghana. These findings inform the interpretation of previous seroprevalence estimates based upon screening assays alone.
Research Interests:
Research Interests:
Research Interests: Thalassemia, Adolescent, Motivation, Greece, Humans, and 7 moreFemale, Male, Aged, Middle Aged, Questionnaires, Adult, and Blood Donors
Research Interests:
The Q80K polymorphism in the HCV NS3 enzyme reduces susceptibility to simeprevir and other novel protease inhibitors. The study aimed to determine the prevalence of Q80K in treatment-naïve HCV-1a carriers in the North-West (NW) and... more
The Q80K polymorphism in the HCV NS3 enzyme reduces susceptibility to simeprevir and other novel protease inhibitors. The study aimed to determine the prevalence of Q80K in treatment-naïve HCV-1a carriers in the North-West (NW) and South-East (SE) of England, investigate occurrence of Q80K as a minority variant, and characterise viral phylogeny. Plasma samples from subjects that were naïve to anti-HCV therapy underwent conventional (Sanger) and deep (Illumina-Miseq, 1% interpretative cut-off) sequencing of NS3. Q80K occurred in 44/238 subjects (18.5%, 95% confidence interval 13.6%-23.4%), including 19/70 (27.1%) in the NW and 25/168 (14.9%) in the SE (p=0.0425), with no difference by HCV RNA load or HIV status. Q80K frequencies in reads of samples that underwent Illumina sequencing were >40% in all cases. Among subjects with Q80K, 5/44 (11.4%) showed one additional major resistance-associated mutation in NS3 detected at mutant frequency above (V36L, V55A) or below (V36M) 10%. Phylogenetic analyses identified the two recognised HCV-1a lineages with (clade I) and without (clade II) Q80K. Overall, 148/238 (62.2%) sequences occurred within regional or inter-regional clusters, each comprising 3-20 sequences. There was no unique clustering of English sequences relative to strains from continental Europe and North America. In conclusion, Q80K was found at high prevalence among treatment-naïve HCV-1a carriers in England, and was reliably detected by conventional sequencing, with no increased detection by deep sequencing. English sequences were highly interspersed with sequences from elsewhere in Europe (clade II) and North America (clade I), and their phylogeny was consistent with multiple introductions from different areas.
Research Interests:
There is progressive concern about the evolving burden of morbidity and mortality caused by coinfection with HIV-1 and hepatitis B virus (HBV) in sub-Saharan Africa, but the epidemiology and impact of this problem are not well defined. We... more
There is progressive concern about the evolving burden of morbidity and mortality caused by coinfection with HIV-1 and hepatitis B virus (HBV) in sub-Saharan Africa, but the epidemiology and impact of this problem are not well defined. We therefore set out to assimilate more information about the nature of HBV/HIV coinfection in this region by undertaking a retrospective observational study of southern African adult women. We used samples from previously recruited HIV-1 positive women attending antenatal clinics in three settings in South Africa and Botswana (n = 950) and added a small cohort of HIV-negative antenatal South African women for comparison (n = 72). We tested for HBsAg and followed up HBsAg-positive samples by testing for HBeAg, HBV DNA, HBV genotype, presence of drug-resistance associated mutations (RAMs) and HDV. We identified HBsAg in 72 individuals (7% of the whole cohort), of whom 27% were HBeAg-positive, and the majority HBV genotypes A1 and A2. We did not detect any HDV coinfection. HBV prevalence was significantly different between geographically distinct cohorts, but did not differ according to HIV status. Among adults from South Africa, HBV/HIV coinfected patients had lower CD4+ T cell counts compared to those with HIV-monoinfection (p = 0.02), but this finding was not replicated in the cohort from Botswana. Overall, these data provide a snapshot of the coinfection problem at the heart of the HIV/HBV co-epidemic, and are important to inform public health policy, resource allocation, education, surveillance and clinical care.
Research Interests:
After the infusion of HIV-1 virus into a host cell, RNA is reverse transcribed to dsDNA, which persists intracellular to the infected cell in a variety of forms. Numerous in-house assays have been developed for the quantification of the... more
After the infusion of HIV-1 virus into a host cell, RNA is reverse transcribed to dsDNA, which persists intracellular to the infected cell in a variety of forms. Numerous in-house assays have been developed for the quantification of the different cellular HIV-1 DNA forms; these implement conventional or real-time PCR methodology. In this review we discuss recent findings about the longitudinal monitoring of cell-associated HIV-1 DNA in naïve and pre-treated patients, as a marker for clinical progression, treatment initiation and long-term success of HAART. These findings underline the importance of monitoring HIV-1 DNA in clinical practice, in addition to HIV-RNA and CD4(+) T Cell counts, for the better assessment of HIV-treatment and disease progression. The lack of a standardized real-time PCR assay is major impediment to more wide-spread HIV-1 DNA monitoring.
Research Interests:
The purpose of this study was to describe and highlight the work of the so called "atomic" philosophers Leucippus and in particular, his student Democritus, after an extensive research of works written by numerous ancient Greek... more
The purpose of this study was to describe and highlight the work of the so called "atomic" philosophers Leucippus and in particular, his student Democritus, after an extensive research of works written by numerous ancient Greek philosophers and historians. The work of these two philosophers is groundbreaking, covers a wide spectrum of science and humanities and shows their high level of scholarship, erudition, and analytical thinking. Their ideas are often mentioned by other ancient Greek philosophers, with positive and sometimes negative criticism. Their theories were spread later, in ancient Rome, Byzantium, the Medieval Western Europe and in our times.
Research Interests:
This study outlines the major landmarks in the research on scurvy and its relationship to vitamin C. A thorough search including original manuscripts, books and contemporary reviews published in PubMed was conducted using as keywords... more
This study outlines the major landmarks in the research on scurvy and its relationship to vitamin C. A thorough search including original manuscripts, books and contemporary reviews published in PubMed was conducted using as keywords “scurvy”, “vitamin C”, and “history of medicine”. Observations on scurvy first appear in Egyptian medical scrolls 3500years ago, and continue through to the discovery of
Research Interests:
The aim of this study was to elevate from obscurity the results of Demetrios Kouretas' research on the drug addicts in the Hellenic Armed forces during the mid-war period. Demetrios Kouretas, gifted with exceptional discernment,... more
The aim of this study was to elevate from obscurity the results of Demetrios Kouretas' research on the drug addicts in the Hellenic Armed forces during the mid-war period. Demetrios Kouretas, gifted with exceptional discernment, undertook a pioneering study regarding the use of addictive substances in the Greek Armed forces. Kouretas did not stick to the epidemiological parameters of the
Research Interests:
Previous studies showed that high levels of human immunodeficiency virus type 1 (HIV-1) DNA are associated with a faster progression to AIDS, an increased risk of death, and a higher risk of HIV RNA rebound in patients on highly active... more
Previous studies showed that high levels of human immunodeficiency virus type 1 (HIV-1) DNA are associated with a faster progression to AIDS, an increased risk of death, and a higher risk of HIV RNA rebound in patients on highly active antiretroviral therapy. Our objective was to develop and assess a highly sensitive real-time multiplex PCR assay for the quantification of
Research Interests:
Research Interests:
Antiretroviral treatment (ART) programs in sub-Saharan Africa have for many years included lamivudine as the sole HBV inhibitor. Long-term outcomes, and the effects of introducing tenofovir as part of ART in these populations, have not... more
Antiretroviral treatment (ART) programs in sub-Saharan Africa have for many years included lamivudine as the sole HBV inhibitor. Long-term outcomes, and the effects of introducing tenofovir as part of ART in these populations, have not been characterized. The study comprised a cross-sectional analysis of 106 HIV-HBV co-infected subjects maintained on lamivudine, and a prospective analysis of 76 lamivudine-experienced subjects who introduced tenofovir. Patients underwent assessment of liver fibrosis by transient elastography (TE) and testing to characterize HIV-1 and HBV replication. After median 45 months of lamivudine, HIV-1 RNA and HBV DNA were detectable in 35/106 (33.0%) and 54/106 (50.9%) subjects respectively, with corresponding drug-resistance rates of 17/106 (16.0%) and 31/106 (29.2%). TE values were median 5.7 kPa (IQR 4.7, 7.2) and independently associated with HBV DNA load, AST levels, and platelet counts; 13/106 (12.3%) subjects had TE measurements >9.4 kPa. Twelve...
Research Interests:
ART) has dramatically reduced morbidity and mortality associated with HIV/AIDS. However, this has left a niche for the emergence of liver disease in HIV-positive individuals co-infected with hepatitis viruses. Chronic liver disease and... more
ART) has dramatically reduced morbidity and mortality associated with HIV/AIDS. However, this has left a niche for the emergence of liver disease in HIV-positive individuals co-infected with hepatitis viruses. Chronic liver disease and hepatocellular carcinoma now account for a significant, and continually increasing, burden of disease in the context of HIV [1,2,3]. Despite the geographical overlap between highly endemic Hepatitis B Virus (HBV) and HIV-1 in Southern Africa, there is variable estimation of the prevalence of co-infection in different populations (Fig. 1). There are very few studies that report the characteristics of HBV in individuals with HIV, and there are conflicting data from Africa about the extent to which HBV and HIV impact on one another clinically.
It has been proposed that hepatitis B virus (HBV) sub-genotype A1 infections have mild outcomes and a low risk of drug-resistance among patients infected with human immunodeficiency virus (HIV) receiving lamivudine-containing... more
It has been proposed that hepatitis B virus (HBV) sub-genotype A1 infections have mild outcomes and a low risk of drug-resistance among patients infected with human immunodeficiency virus (HIV) receiving lamivudine-containing antiretroviral therapy (ART) without tenofovir in Africa. The virologic expression of HBV sub-genotype A1 coinfection was studied over 12 months in HIV-positive adults starting stavudine/lamivudine/nevirapine in Malawi, using Sanger, deep, clonal, and single full-genome sequencing for the sensitive characterization of HBV resistance-associated mutations (RAMs). Among 1117 subjects, 133 (12%) tested HBsAg-positive. After starting ART, retention rates were 96/133 (72%) at 6 months and 54/133 (41%) at 12 months. Based upon the last available follow-up, 92/96 (96%) subjects achieved HIV-1 RNA <40 copies/mL, 48/96 (50%) showed HBV DNA <14 IU/mL, and 24/96 (25%) acquired HBV RAMs. At 6 months, M204I was detected in 8/46 (17%) and 16/17 (94%) subjects using Sang...
Research Interests:
Research Interests:
Research Interests:
Research Interests: Treatment Outcome, Biological Sciences, Pregnancy, Humans, Low Dose, and 17 moreFemale, Ovulation Induction, Statistical Significance, Cost effectiveness, Gene Dosage, Molecular endocrinology and reproductive biology, Adult, Time Factors, Prognosis, Reproductive, Fertilization in Vitro, Lymphocytes, Pilot Projects, Recombinant Proteins, Female Infertility, Pregnancy Rate, and Follicle stimulating hormone
Research Interests:
Research Interests: Clinical Microbiology, Biological Sciences, real time PCR, Hepatitis B, Humans, and 13 moreDrug Resistance, Polymerase Chain Reaction, Early Detection, Genotype, Adverse Event, Microbial Sensitivity Tests, In Vitro Studies, Hepatitis B virus, Sensitivity and Specificity, Amplification Refractory Mutation System, Nucleotides, Molecular beacon, and Dna Synthesis
Research Interests:
Research Interests:
Research Interests:
The present study summarizes the history of research on cardiac metabolism from antiquity till the 21st century. It describes important landmarks regarding the discovery of oxygen and of the 3 steps of cellular respiration, as well as... more
The present study summarizes the history of research on cardiac metabolism from antiquity till the 21st century. It describes important landmarks regarding the discovery of oxygen and of the 3 steps of cellular respiration, as well as major research on cardiac energy metabolism. For this purpose, we conducted a thorough search of original manuscripts, books, and contemporary reviews published in PubMed. The first views and concepts about the heart&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s function appear in Greek philosophic manuscripts of 2500 years ago. According to Aristotle, the heart is responsible for heat production, which is essential for life. The understanding of cardiac metabolism awaited new discoveries. The discovery of oxygen during the 18th century, along with the idea of energy conservation, or what is now known as one of the first versions of the first law of thermodynamics, played an important role in initiating the study of energy metabolism in general and heart metabolism later. The discovery of glycolysis, of the Krebs cycle, and of adenosine triphosphate offered a better understanding of cellular respiration, necessary for later research. Indeed, many researchers dedicated their studies to energy metabolism, but Richard John Bing, the renowned German research cardiologist, is the one who guided the exploration of cardiac metabolism, and he is therefore considered to be the father of cardiac energy metabolism. Since then, encouraging new research has been taking place, offering important clinical applications for heart patients.