Publications
192 results found
Singh G, Nelson M, Hicks G, et al., 2016, Baseline telaprevir (TVR) resistance mutations do not predict failure in the response guided treatment of genotype 1 acute hepatitis C (HCV) in individuals with HIV co-infection, HIV Medicine, Vol: 17, Pages: 26-26, ISSN: 1464-2662
Horner PJ, Wills GS, Righarts A, et al., 2016, Chlamydia trachomatis Pgp3 antibody persists and correlates with self-reported infection and behavioural risks in a blinded cohort study, PLOS One, Vol: 11, ISSN: 1932-6203
Erlwein O, Sweeney NP, de Leon R, et al., 2015, Determination of sequences required for HERV-K transduction and its recognition by foreign retroviral virions, Journal of Virology, Vol: 90, Pages: 3243-3246, ISSN: 1098-5514
Sequences necessary for transduction of HERV-Kcon, a consensus of the HERV-K(HML-2) family were analysed and found to reside in the leader/gag region. They act in an orientation-dependent way and consist of at least two sites working together. Having defined these sequences, we exploited this information to produce a simple system to investigate to what extent virions of HERV-Kcon, MLV and HIV-1 have the ability to transduce each other's genomes, leading to potential contamination of gene therapy vectors.
Hoehn KB, Gall A, Bashford-Rogers R, et al., 2015, Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436
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- Citations: 19
Thompson CC, Griffiths C, Nicod SS, et al., 2015, The Rsb phosphoregulatory network controls availability of the primary sigma factor in Chlamydia trachomatis and influences the kinetics of growth and development, PLOS Pathogens, Vol: 11, Pages: 1-22, ISSN: 1553-7366
Chlamydia trachomatis is the leading cause of both bacterial sexually transmitted infection and infection-derived blindness world-wide. No vaccine has proven protective to date in humans. C. trachomatis only replicates from inside a host cell, and has evolved to acquire a variety of nutrients directly from its host. However, a typical human immune response will normally limit the availability of a variety of essential nutrients. Thus, it is thought that the success of C. trachomatis as a human pathogen may lie in its ability to survive these immunological stress situations by slowing growth and development until conditions in the cell have improved. This mode of growth is known as persistence and how C. trachomatis senses stress and responds in this manner is an important area of research. Our report characterizes a complete signaling module, the Rsb network, that is capable of controlling the growth rate or infectivity of Chlamydia. By manipulating the levels of different pathway components, we were able to accelerate and restrict the growth and development of this pathogen. Our results suggest a mechanism by which Chlamydia can tailor its growth rate to the conditions within the host cell. The disruption of this pathway could generate a strain incapable of surviving a typical human immune response and would represent an attractive candidate as an attenuated growth vaccine.
Hamlyn E, Stoehr W, Cooper DA, et al., 2015, The effect of short-course antiretroviral therapy initiated in primary HIV-1 infection on interleukin-6 and D-dimer levels, AIDS, Vol: 29, Pages: 1355-1361, ISSN: 0269-9370
Objective: Interruption of antiretroviral therapy (ART) in chronic HIV disease is associated with increased mortality, predicted by elevations in interleukin-6 (IL-6) and D-dimer. The effect of ART interruption in primary HIV-1 infection on these biomarkers is unknown.Methods: Plasma samples from 200 HIV seroconverters enrolled in the Short Pulse Anti-Retroviral Therapy At HIV Seroconversion trial of deferred ART (standard of care) – 12 or 48 week ART (ART12 or ART48, respectively) – were analysed for IL-6 and D-dimer at weeks 0, 12, 16, 48, 52, 60 and 108 after randomization. Changes in log10 levels from weeks 0 to 12 were analysed using linear regression, as were changes from baseline to 4 weeks after stopping ART. Areas under the biomarker–time curves (AUC) to week 108 were adjusted for baseline values, and compared across all arms.Results: Median (inter-quartile range) baseline IL-6 and D-dimer were 1.45 (0.88, 2.41) pg/ml and 0.34 (0.20, 0.50) mg/l, respectively. At week 12, D-dimer levels were significantly lower among treated compared to untreated individuals (P < 0.001), whereas IL-6 levels were similar (P = 0.23). Within 4 weeks from stopping ART, IL-6 and D-dimer levels rose by 22 and 18%, reaching pre-ART levels. Over 108-week follow-up, there was no difference between arms in IL-6 AUC (P = 0.53), but D-dimer AUC was significantly lower for ART12 and ART48 compared to standard of care (overall P = 0.008).Conclusion: Stopping ART in primary HIV-1 infection leads to inflammatory biomarker rebound to pre-treatment levels. However, over 108-week follow-up, we found no evidence that biomarker levels were higher for those interrupting ART, compared to those remaining ART-naïve, and D-dimer levels were significantly lower.
Martin TCS, Singh GJ, McClure M, et al., 2015, HCV Reinfection Among HIV-Positive Men Who Have Sex With Men: A Pragmatic Approach, HEPATOLOGY, Vol: 61, Pages: 1437-1437, ISSN: 0270-9139
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- Citations: 5
Tipple C, Jones R, McClure M, et al., 2015, Rapid <i>Treponema pallidum</i> Clearance from Blood and Ulcer Samples following Single Dose Benzathine Penicillin Treatment of Early Syphilis, PLOS NEGLECTED TROPICAL DISEASES, Vol: 9, ISSN: 1935-2735
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- Citations: 12
Vera JH, Garvey LJ, Allsop JM, et al., 2015, Alterations in Cerebrospinal Fluid Chemokines Are Associated With Maraviroc Exposure and In Vivo Metabolites Measurable by Magnetic Resonance Spectroscopy, HIV CLINICAL TRIALS, Vol: 13, Pages: 222-227, ISSN: 1528-4336
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- Citations: 10
Nye LC, Gray N, McClure M, et al., 2015, Identification of a novel human circulating metabolite of tenofovir disoproxil fumarate with LC-MS/MS, BIOANALYSIS, Vol: 7, Pages: 643-652, ISSN: 1757-6180
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- Citations: 7
Berkhout B, Bodem J, Erlwein O, et al., 2014, Obituary: Axel Rethwilm (1959-2014), RETROVIROLOGY, Vol: 11
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- Citations: 2
Hamlyn E, Fidler S, Stoehr W, et al., 2014, Interleukin-6 and D- dimer levels at seroconversion as predictors of HIV-1 disease progression, AIDS, Vol: 28, Pages: 869-874, ISSN: 0269-9370
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- Citations: 23
Stoehr W, Fidler S, McClure M, et al., 2013, Duration of HIV-1 Viral Suppression on Cessation of Antiretroviral Therapy in Primary Infection Correlates with Time on Therapy, PLoS ONE, Vol: 8, ISSN: 1932-6203
Objective: A minority of HIV-1 positive individuals treated with antiretroviral therapy (ART) in primary HIV-1 infection(PHI) maintain viral suppression on stopping. Whether this is related to ART duration has not been explored.Design: And Methods: Using SPARTAC trial data from individuals recruited within 6 months of seroconversion, wepresent an observational analysis investigating whether duration of ART was associated with post-treatment viraemiccontrol. Kaplan-Meier estimates, logistic regression and Cox models were used.Results: 165 participants reached plasma viral loads (VL) <400 copies/ml at the time of stopping therapy (ART stop).After ART stop, 159 experienced confirmed VL ≥400 copies/ml during median (IQR) follow-up of 167 (108,199)weeks.Most participants experienced VL rebound within 12 weeks from ART stop, however, there was a suggestion of ahigher probability of remaining <400 copies/ml for those on ART >12 weeks compared to ≤12 weeks (p=0.061).Cumulative probabilities of remaining <400 copies/ml at 12, 52 and 104 weeks after ART stop were 21%(95%CI=13,30), 4% (1,9), and 4% (1,9) for ≤12 weeks ART, and 32% (22,42), 14% (7,22), and 5% (2,11) for >12weeks.In multivariable regression, ART for >12 weeks was independently associated with a lower probability of being≥400 copies/ml within 12 weeks of ART stop (OR=0.11 (95%CI=0.03,0.34), p<0.001)). In Cox models of time to VL≥400 after 12 weeks, we only found an association with female sex (OR=0.2, p=0.001).Conclusion: Longer ART duration in PHI was associated with a higher probability of viral control after ART stop.
Horner P, Soldan K, Vieira SM, et al., 2013, C. trachomatis pgp3 antibody prevalence in young women in England, 1993-2010, PLOS One, Vol: 8, ISSN: 1932-6203
Seroepidemiology of chlamydia can offer study opportunities and insights into cumulative risk of exposure that may contribute to monitoring the frequency of, and control of, genital chlamydia–the most commonly diagnosed STI in England. We undertook retrospective anonymous population-based cross-sectional surveys using an indirect IgG ELISA for chlamydia Pgp3 antibody. Sera from 4,732 women aged 17–24 years were tested. Samples were taken at 3-yearly intervals between 1993 and 2002, a period during which other data suggest chlamydia transmission may have been increasing, and from each year between 2007 and 2010. Seroprevalence increased in 17–24 year olds over time between 1993 and 2002. Between 2007 and 2010, age-standardised seroprevalence among 17–24 year olds decreased from 20% (95% CI: 17–23) to 15% (95%CI 12–17) (p = 0.0001). The biggest drop was among 20 to 21 year olds, where seroprevalence decreased from 21% in 2007 to 9% in 2010 (p = 0.002). These seroprevalence data reflect some known features of the epidemiology of chlamydia infection, and show that exposure to antibody-inducing chlamydia infection has declined in recent years. This decline was concurrent with increasing rates of screening for asymptomatic chlamydia. Serology should be explored further as a tool for evaluation of chlamydia control, including chlamydia screening programmes.
Horner PJ, Wills GS, Reynolds R, et al., 2013, Effect of time since exposure to <i>Chlamydia trachomatis</i> on chlamydia antibody detection in women: a cross-sectional study, SEXUALLY TRANSMITTED INFECTIONS, Vol: 89, Pages: 398-403, ISSN: 1368-4973
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- Citations: 50
Singh S, Kaye S, Francis N, et al., 2013, Human endogenous retrovirus K (HERV-K) rec mRNA is expressed in primary melanoma but not in benign naevi or normal skin, PIGMENT CELL & MELANOMA RESEARCH, Vol: 26, Pages: 426-428, ISSN: 1755-1471
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- Citations: 18
Sweeney N, Regan C, Liu J, et al., 2013, Gene therapy for metachromatic leukodystrophy using foamy virus vector, Conference of the British-Society-for-Gene-and-Cell-Therapy (BSGCT), Publisher: MARY ANN LIEBERT INC, Pages: A27-A27, ISSN: 1043-0342
Khan A, Fu H, Tan LA, et al., 2013, Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition, EUROPEAN JOURNAL OF IMMUNOLOGY, Vol: 43, Pages: 734-746, ISSN: 0014-2980
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- Citations: 18
Gall A, Kaye S, Hue S, et al., 2013, Restriction of V3 region sequence divergence in the HIV-1 envelope gene during antiretroviral treatment in a cohort of recent seroconverters, Retrovirology, Vol: 10, ISSN: 1742-4690
Background: Dynamic changes in Human Immunodeficiency Virus 1 (HIV-1) sequence diversity and divergence areassociated with immune control during primary infection and progression to AIDS. Consensus sequencing or singlegenome amplification sequencing of the HIV-1 envelope (env) gene, in particular the variable (V) regions, is used asa marker for HIV-1 genome diversity, but population diversity is only minimally, or semi-quantitatively sampledusing these methods.Results: Here we use second generation deep sequencing to determine inter-and intra-patient sequenceheterogeneity and to quantify minor variants in a cohort of individuals either receiving or not receivingantiretroviral treatment following seroconversion; the SPARTAC trial. We show, through a cross-sectional study ofsequence diversity of the env V3 in 30 antiretroviral-naive patients during primary infection that considerablepopulation structure diversity exists, with some individuals exhibiting highly constrained plasma virus diversity.Diversity was independent of clinical markers (viral load, time from seroconversion, CD4 cell count) of infection.Serial sampling over 60 weeks of non-treated individuals that define three initially different diversity profiles showedthat complex patterns of continuing HIV-1 sequence diversification and divergence could be readily detected.Evidence for minor sequence turnover, emergence of new variants and re-emergence of archived variants could beinferred from this analysis. Analysis of viral divergence over the same time period in patients who received short(12 weeks, ART12) or long course antiretroviral therapy (48 weeks, ART48) and a non-treated control group revealedthat ART48 successfully suppressed viral divergence while ART12 did not have a significant effect.Conclusions: Deep sequencing is a sensitive and reliable method for investigating the diversity of the env V3 as animportant component of HIV-1 genome diversity. Detailed insights into the complex early intra-patie
Fidler S, Porter K, Ewings F, et al., 2013, Short-Course Antiretroviral Therapy in Primary HIV Infection, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 368, Pages: 207-217, ISSN: 0028-4793
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- Citations: 163
McClure M, Singh GJ, Rayment M, et al., 2012, Clinical outcomes of a combined HIV and renal clinic, Clinical Kidney Journal, Vol: 5, Pages: 530-534, ISSN: 2048-8505
BACKGROUND: Renal disease is an emerging problem in patients living with human immunodeficiency virus (HIV), as illustrated by an increased incidence of acute kidney injury and chronic kidney disease (CKD) from HIV, its associated treatment and comorbidities such as diabetes and vascular disease. We have established a combined HIV-renal clinic to manage such patients, enhance their treatment and minimize outpatient visits. METHODS: We have analysed the outcomes of the first 99 patients seen in the clinic using electronic patient records. These ninety-nine patients were referred to the service from HIV physicians in West London and all the patients were seen jointly by an HIV and a renal consultant. RESULTS: Sixty-five percent of the patients were referred with reduced renal function or proteinuria [mean creatinine at presentation 136 mcmol/L, estimated glomerular filtration rate (eGFR) 57 mL/min/1.73 m(2)]. The majority (53%) had risk factors predisposing to vascular disease including diabetes, hypertension, previous stroke or myocardial infarction. Overall, 27% of patients had a renal diagnosis directly associated with HIV (HIVAN, immune complex nephritis, tenofovir toxicity, Fanconi syndrome), 73% had an alternative possible cause. Twenty-seven percent of patients had low-level proteinuria (urine protein:creatinine ratio abnormal but <100 mg/mmol) or mildly reduced eGFR (40-66 mL/min/1.73 m(2)) without a clear underlying cause. Ten percent of patients were thought to have tenofovir-induced renal damage all of whom improved on cessation of this agent. Following the review in the combined clinic, 64% of patients had a change in treatment or management, with 50% improving their renal parameters as a result. Most patients were discharged back to their main HIV teams for ongoing follow-up. CONCLUSIONS: A combined HIV-renal clinic can enhance patient care with reduced outpatient visits.
Hamlyn E, Ewings FM, Porter K, et al., 2012, Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection, PLoS ONE, Vol: 7, ISSN: 1932-6203
Objectives: The magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onwardtransmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIVinfection (CHI).Design: Two populations with protocol-indicated ART cessation from SPARTAC (PHI, n = 182) and SMART (CHI, n = 1450)trials.Methods: Time for pVL to reach pre-ART levels after stopping ART was assessed in PHI using survival analysis. Differences inpVL between PHI and CHI populations 4 weeks after stopping ART were examined using linear and logistic regression.Differences in pVL slopes up to 48 weeks were examined using linear mixed models and viral burden was estimatedthrough a time-averaged area-under-pVL curve. CHI participants were categorised by nadir CD4 at ART stop.Results: Of 171 PHI participants, 71 (41.5%) rebounded to pre-ART pVL levels, at a median of 50 (95% CI 48–51) weeks afterstopping ART. Four weeks after stopping treatment, although the proportion with pVL$400 copies/ml was similar (78% PHIversus 79% CHI), levels were 0.45 (95% CI 0.26–0.64) log10 copies/ml lower for PHI versus CHI, and remained lower up to 48weeks. Lower CD4 nadir in CHI was associated with higher pVL after ART stop. Rebound for CHI participants with CD4 nadir.500 cells/mm3 was comparable to that experienced by PHI participants.Conclusions: Stopping ART initiated in PHI and CHI was associated with viral rebound to levels conferring increasedtransmission risk, although the level of rebound was significantly lower and sustained in PHI compared to CHI.
Hamlyn E, Hickling S, Porter K, et al., 2012, Increased levels of CD4 T-cell activation in individuals with CXCR4 using viruses in primary HIV-1 infection, 18th Conference on Retroviruses and Opportunistic Infections (CROI), Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 887-890, ISSN: 0269-9370
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- Citations: 14
Lai RPJ, Yan J, Heeney J, et al., 2011, Nef Decreases HIV-1 Sensitivity to Neutralizing Antibodies that Target the Membrane-proximal External Region of TMgp41, PLOS PATHOGENS, Vol: 7, ISSN: 1553-7366
Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs) that target the membrane proximal external region (MPER) of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly discovered activit
Robinson MJ, Erlwein O, McClure MO, 2011, Counterpoint: XMRV does not cause chronic fatigue, Trends in Microbiology
Tipple C, McClure MO, Taylor GP, 2011, High prevalence of macrolide resistant <i>Treponema pallidum</i> strains in a London centre, SEXUALLY TRANSMITTED INFECTIONS, Vol: 87, Pages: 486-488, ISSN: 1368-4973
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- Citations: 52
Tipple C, Hanna MOF, Hill S, et al., 2011, Getting the measure of syphilis: qPCR to better understand early infection, SEXUALLY TRANSMITTED INFECTIONS, Vol: 87, Pages: 479-485, ISSN: 1368-4973
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- Citations: 39
Erlwein O, Robinson MJ, Dustan S, et al., 2011, DNA extraction columns contaminated with murine sequences, PLOS One, Vol: 6, ISSN: 1932-6203
Sequences of the novel gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV) have been described in human prostate cancer tissue, although the amounts of DNA are low. Furthermore, XMRV sequences and polytropic (p) murine leukemia viruses (MLVs) have been reported in patients with chronic fatigue syndrome (CFS). In assessing the prevalence of XMRV in prostate cancer tissue samples we discovered that eluates from naïve DNA purification columns, when subjected to PCR with primers designed to detect genomic mouse DNA contamination, occasionally gave rise to amplification products. Further PCR analysis, using primers to detect XMRV, revealed sequences derived from XMRV and pMLVs from mouse and human DNA and DNA of unspecified origin. Thus, DNA purification columns can present problems when used to detect minute amounts of DNA targets by highly sensitive amplification techniques.
English S, Katzourakis A, Bonsall D, et al., 2011, Phylogenetic analysis consistent with a clinical history of sexual transmission of HIV-1 from a single donor reveals transmission of highly distinct variants, Retrovirology, Vol: 8, ISSN: 1742-4690
Background: To combat the pandemic of human immunodeficiency virus 1 (HIV-1), a successful vaccine will needto cope with the variability of transmissible viruses. Human hosts infected with HIV-1 potentially harbour many viralvariants but very little is known about viruses that are likely to be transmitted, or even if there are viralcharacteristics that predict enhanced transmission in vivo. We show for the first time that genetic divergenceconsistent with a single transmission event in vivo can represent several years of pre-transmission evolution.Results: We describe a highly unusual case consistent with a single donor transmitting highly related but distinctHIV-1 variants to two individuals on the same evening. We confirm that the clustering of viral genetic sequences,present within each recipient, is consistent with the history of a single donor across the viral env, gag and polgenes by maximum likelihood and Bayesian Markov Chain Monte Carlo based phylogenetic analyses. Based on anuncorrelated, lognormal relaxed clock of env gene evolution calibrated with other datasets, the time since themost recent common ancestor is estimated as 2.86 years prior to transmission (95% confidence interval 1.28 to4.54 years).Conclusion: Our results show that an effective design for a preventative vaccine will need to anticipate extensiveHIV-1 diversity within an individual donor as well as diversity at the population level.
White P, Fox J, MacDonald N, et al., 2011, HOW MANY INFECTIONS ARE AVERTED BY BEHAVIOUR CHANGE AFTER EARLY HIV DIAGNOSIS & COUNSELLING OF MSM? ESTIMATES FROM A STOCHASTIC INDIVIDUAL-BASED MODEL, SEXUALLY TRANSMITTED INFECTIONS, Vol: 87, Pages: A51-A52, ISSN: 1368-4973
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