Publications
518 results found
Perry MEO, Taylor GP, Sabin CA, et al., 2015, Lopinavir and atazanavir in pregnancy: comparable infant outcomes, virological efficacies and preterm delivery rates, HIV Medicine, Vol: 17, Pages: 28-35, ISSN: 1464-2662
Honarbakhsh S, Taylor GP, 2015, High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease., BMC Infectious Diseases, Vol: 15, ISSN: 1471-2334
BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. METHODS: A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. RESULT: 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). CONCLUSIONS: Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis.
Bangham CRM, Araujo A, Yamano Y, et al., 2015, HTLV-1-associated myelopathy/tropical spastic paraparesis, NATURE REVIEWS DISEASE PRIMERS, Vol: 1, ISSN: 2056-676X
Bangham CRM, Araujo A, Yamano Y, et al., 2015, HTLV-1-associated myelopathy/tropical spastic paraparesis (vol 1, 15012, 2015), NATURE REVIEWS DISEASE PRIMERS, Vol: 1, ISSN: 2056-676X
Demontis MA, Sadiq MT, Golz S, et al., 2015, HTLV-1 viral RNA is detected rarely in plasma of HTLV-1 infected subjects., Journal of Medical Virology, Vol: 120, Pages: 4080-4101, ISSN: 1096-9071
Plasma of patients infected with HTLV-1 is considered non-infectious but detection of HTLV-1 genomic RNA in plasma has been recently reported. The aim of this project was to detect and quantify HTLV-1 RNA in plasma and assess its potential value in diagnosis and prognosis. RNA from 1 ml of plasma from 65 subjects infected with HTLV-1 (27 asymptomatic carriers [AC]), 17 patients with HTLV-1-associated myelopathy (HAM/TSP), 14 with adult T-cell leukemia/lymphoma (ATLL), two co-infected with HIV, and five with other HTLV-1-associated disease, was extracted and reverse transcribed. HTLV-1 specific nested PCR was performed using primers to amplify the conserved Tax region. All samples were run in quadruplicate, nested PCR products were detected by gel electrophoresis. HTLV-1 RNA was detected in plasma from 18 (28%) patients, always at a very low copy number (3-13 copies viral cDNA per milliliter of plasma). Mean values of HTLV-1 proviral load did not differ between patients in whom HTLV-1 RNA was detected and patients in whom it was not possible to detect HTLV-1 RNA in plasma. HTLV-1 genomic RNA can be detected in the plasma of a minority of patients but not at a level or frequency to be useful clinically or diagnostically. Lack of transmission of HTLV-1 by plasma is due to the rare presence of HTLV-1 virions, regardless of any other factor. J. Med. Virol. © 2015 Wiley Periodicals, Inc.
Peters H, Byrne L, De Ruiter A, et al., 2015, Duration of ruptured membranes and mother-to-child HIV transmission: a prospective population-based surveillance study, BJOG: An International Journal of Obstetrics and Gynaecology, Vol: 123, Pages: 975-981, ISSN: 1471-0528
Pollock KM, Montamat-Sicotte DJ, Cooke GS, et al., 2015, Differences in antigen-specific CD4+ responses to opportunistic infections in HIV infection, Immunity, Inflammation and Disease, Vol: 3, Pages: 141-153, ISSN: 2050-4527
HIV-infected individuals with severe immunodeficiency are at risk of opportunistic infection (OI). Tuberculosis (TB) may occur without substantial immune suppression suggesting an early and sustained adverse impact of HIV on Mycobacterium tuberculosis (MTB)-specific cell mediated immunity (CMI). This prospective observational cohort study aimed to observe differences in OI-specific and MTB-specific CMI that might underlie this. Using polychromatic flow cytometry, we compared CD4+ responses to MTB, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Candida albicans in individuals with and without HIV infection. MTB-specific CD4+ T-cells were more polyfunctional than virus specific (CMV/EBV) CD4+ T-cells which predominantly secreted IFN-gamma (IFN-γ) only. There was a reduced frequency of IFN-γ and IL-2 (IL-2)-dual-MTB-specific cells in HIV-infected individuals, which was not apparent for the other pathogens. MTB-specific cells were less differentiated especially compared with CMV-specific cells. CD127 expression was relatively less frequent on MTB-specific cells in HIV co-infection. MTB-specific CD4+ T-cells PD-1 expression was infrequent in contrast to EBV-specific CD4+ T-cells. The variation in the inherent quality of these CD4+ T-cell responses and impact of HIV co-infection may contribute to the timing of co-infectious diseases in HIV infection.
Huntington S, Thorne C, Newell M-L, et al., 2015, Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy, AIDS, Vol: 29, Pages: 801-809, ISSN: 0269-9370
Objective: The objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART).Design: Two observational studies: the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC).Methods: Combined data from UK CHIC and NSHPC were used to identify factors associated with LEE (grade 1–4) and severe LEE (grade 3–4). Women starting ART in 2000–2012 were included irrespective of pregnancy status. Cox proportional hazards were used to assess fixed and time-dependent covariates including pregnancy status, CD4+ cell count, drug regimen and hepatitis B virus/hepatitis C virus (HBV/HCV) coinfection.Results: One-quarter (25.7%, 982/3815) of women were pregnant during follow-up, 14.2% (n = 541) when starting ART. The rate of LEE was 14.5/100 person-years in and 6.0/100 person-years outside of pregnancy. The rate of severe LEE was 3.9/100 person-years in and 0.6/100 person-years outside of pregnancy. The risk of LEE and severe LEE was increased during pregnancy [LEE: adjusted hazard ratio (aHR) 1.66 (1.31–2.09); severe LEE: aHR 3.57 (2.30–5.54)], including in secondary analyses excluding 541 women pregnant when starting ART. Other factors associated with LEE and severe LEE included lower CD4+ cell count (<250 cells/μl), HBV/HCV coinfection and calendar year.Conclusion: Although few women developed severe LEE, this study provides further evidence that pregnancy is associated with an increased risk of LEE and severe LEE, reinforcing the need for regular monitoring of liver biomarkers during pregnancy.
Taha S, Taylor G, 2015, The strength of the WHO recommendations for the prevention of mother-to-child transmission of HIV, HIV MEDICINE, Vol: 16, Pages: 28-29, ISSN: 1464-2662
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- Citations: 1
Oomeer S, Taylor G, Ruiter A, et al., 2015, Darunavir/ritonavir in pregnancy - a multicentre retrospective analysis, HIV MEDICINE, Vol: 16, Pages: 27-28, ISSN: 1464-2662
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- Citations: 1
Taylor GP, 2015, Human T-cell Lymphotropic virus type 1 (HTLV-1) and HTLV-1-associated myelopathy/tropical spastic paraparesis, Clinical Infectious Diseases, Vol: 61, Pages: 57-58, ISSN: 1537-6591
Tipple C, Taylor GP, 2015, Syphilis testing, typing, and treatment follow-up: a new era for an old disease, CURRENT OPINION IN INFECTIOUS DISEASES, Vol: 28, Pages: 53-60, ISSN: 0951-7375
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- Citations: 29
Colbers A, Molto J, Ivanovic J, et al., 2015, Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 70, Pages: 534-542, ISSN: 0305-7453
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- Citations: 36
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
Colbers A, Hawkins D, Hidalgo-Tenorio C, et al., 2015, Atazanavir exposure is effective during pregnancy regardless of tenofovir use, ANTIVIRAL THERAPY, Vol: 20, Pages: 57-64, ISSN: 1359-6535
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- Citations: 14
Martin F, Inoue E, Cortese ICM, et al., 2015, Timed walk as primary outcome measure of treatment response in clinical trials for HTLV-1-associated myelopathy: a feasibility study., Pilot Feasibility Stud, Vol: 1, ISSN: 2055-5784
BACKGROUND: To advance the treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), randomised controlled therapeutic studies with appropriate and sensitive outcomes are reuired. One candidate outcome is the 10-metre walk test (10MWT), a patient-centred, simple and functional measure. To calculate sample size based on 10MWT as the primary outcome, variability within and between subjects must be known. METHODS: Data on 10MWT from 76 patients with HAM/TSP were prospectively collected from four specialist centres in Brazil, Japan, USA and UK. Data, collected at two time points, 6 months apart, were log transformed and subjected to analysis of covariance. RESULTS: Baseline mean (standard deviation = SD), median 10MWT were 23.5 (18.9), 16.3 s/10 m and at 6 months 24.9 (23.9), 16.4 s/10 m. The mean (SD) % increase in walk time was 5.74 % (28.2 %). After logarithmic transformation, the linear correlation between baseline and 24 weeks 10MWT was r = 0.938. Using these data, it was determined that a randomised controlled trial with 30 participants per group would have 90 % power to detect a 19 % decrease or a 23 % increase in 10MWT. CONCLUSIONS: The intra-patient variability of 10MWT is relatively small in HAM/TSP over 6 months. 10MWT is a feasible outcome measure for a clinical trial in HAM/TSP. To our knowledge, this is the first ever recommendation for the sample size required for trials in HAM/TSP patients.
Rowan AG, Suemori K, Fujiwara H, et al., 2014, Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression, Retrovirology, Vol: 11, ISSN: 1742-4690
BackgroundImmunogenetic evidence indicates that cytotoxic T lymphocytes (CTLs) specific for the weak CTL antigen HBZ limit HTLV-1 proviral load in vivo, whereas there is no clear relationship between the proviral load and the frequency of CTLs specific for the immunodominant antigen Tax. In vivo, circulating HTLV-1-infected cells express HBZ mRNA in contrast, Tax expression is typically low or undetectable. To elucidate the virus-suppressing potential of CTLs targeting HBZ, we compared the ability of HBZ- and Tax-specific CTLs to lyse naturally-infected cells, by co-incubating HBZ- and Tax-specific CTL clones with primary CD4+ T cells from HLA-matched HTLV-1-infected donors. We quantified lysis of infected cells, and tested whether specific virus-induced host cell surface molecules determine the susceptibility of infected cells to CTL-mediated lysis.ResultsPrimary infected cells upregulated HLA-A*02, ICAM-1, Fas and TRAIL-R1/2 in concert with Tax expression, forming efficient targets for both HTLV-1-specific CTLs and CTLs specific for an unrelated virus. We detected expression of HBZ mRNA (spliced isoform) in both Tax-expressing and non-expressing infected cells, and the HBZ26–34 epitope was processed and presented by cells transfected with an HBZ expression plasmid. However, when coincubated with primary cells, a high-avidity HBZ-specific CTL clone killed significantly fewer infected cells than were killed by a Tax-specific CTL clone. Finally, incubation with Tax- or HBZ-specific CTLs resulted in a significant decrease in the frequency of cells expressing high levels of HLA-A*02.ConclusionsHTLV-1 gene expression in primary CD4+ T cells non-specifically increases susceptibility to CTL lysis. Despite the presence of HBZ spliced-isoform mRNA, HBZ epitope presentation by primary cells is significantly less efficient than that of Tax.Keywords: HTLV-1; Retrovirus; Cytotoxic lymphocyte response; CTL; HBZ; Tax; HLA; ICAM-1; Fas
Pimentel A, Reis I, Toomey N, et al., 2014, Using HDAC Inhibitors to Eradicate Adult T-Cell Leukemia-Lymphoma, 56th Annual Meeting of the American-Society-of-Hematology, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Fields P, Demontis M, Cook L, et al., 2014, Achievement of Complete Hematological Remission and Reversal of High HTLV-1 Viral Loads with Anti CCR-4 Monoclonal Antibody Administration in Afro Caribbean Patients with Relapsed Chronic Adult T Cell Leukaemia (ATLL), BLOOD, Vol: 124, ISSN: 0006-4971
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Martin F, Taylor GP, Jacobson S, 2014, Inflammatory manifestations of HTLV-1 and their therapeutic options, EXPERT REVIEW OF CLINICAL IMMUNOLOGY, Vol: 10, Pages: 1531-1546, ISSN: 1744-666X
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- Citations: 86
Huntington S, Thorne C, Anderson J, et al., 2014, Does pregnancy increase the risk of ART-induced hepatotoxicity among HIV-positive women?, JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, Vol: 17, Pages: 5-5
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- Citations: 4
Samuel M, Bradshaw D, Perry M, et al., 2014, Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir., Infectious Diseases in Obstetrics & Gynecology, Vol: 2014, Pages: 961375-961375, ISSN: 1064-7449
INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy.
de Ruiter A, Taylor GP, Clayden P, et al., 2014, British HIV Association guidelines for the management of HIV infection in pregnant women 2012 (2014 interim review), HIV MEDICINE, Vol: 15, Pages: 1-77, ISSN: 1464-2662
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- Citations: 45
Desrames A, Cassar O, Gout O, et al., 2014, Northern African Strains of Human T-Lymphotropic Virus Type 1 Arose from a Recombination Event, JOURNAL OF VIROLOGY, Vol: 88, Pages: 9782-9788, ISSN: 0022-538X
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- Citations: 15
Abbara A, Brooks T, Taylor GR, et al., 2014, Lessons for Control of Heroin-Associated Anthrax in Europe from 2009-2010 Outbreak Case Studies, London, UK, EMERGING INFECTIOUS DISEASES, Vol: 20, Pages: 1115-1122, ISSN: 1080-6040
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- Citations: 17
Cook LB, Melamed A, Niederer H, et al., 2014, The role of HTLV-1 clonality, proviral structure, and genomic integration site in adult T-cell leukemia/lymphoma, Blood, Vol: 123, Pages: 3925-3931, ISSN: 0006-4971
Adult T-cell leukemia/lymphoma (ATL) occurs in ∼5% of human T-lymphotropic virus type 1 (HTLV-1)–infected individuals and is conventionally thought to be a monoclonal disease in which a single HTLV-1+ T-cell clone progressively outcompetes others and undergoes malignant transformation. Here, using a sensitive high-throughput method, we quantified clonality in 197 ATL cases, identified genomic characteristics of the proviral integration sites in malignant and nonmalignant clones, and investigated the proviral features (genomic structure and 5′ long terminal repeat methylation) that determine its capacity to express the HTLV-1 oncoprotein Tax. Of the dominant, presumed malignant clones, 91% contained a single provirus. The genomic characteristics of the integration sites in the ATL clones resembled those of the frequent low-abundance clones (present in both ATL cases and carriers) and not those of the intermediate-abundance clones observed in 24% of ATL cases, suggesting that oligoclonal proliferation per se does not cause malignant transformation. Gene ontology analysis revealed an association in 6% of cases between ATL and integration near host genes in 3 functional categories, including genes previously implicated in hematologic malignancies. In all cases of HTLV-1 infection, regardless of ATL, there was evidence of preferential survival of the provirus in vivo in acrocentric chromosomes (13, 14, 15, 21, and 22).
Townsend C, Harding K, Peters H, et al., 2014, 5.1 Ruptured membranes and risk of vertical transmission in women with HIV., Arch Dis Child Fetal Neonatal Ed, Vol: 99 Suppl 1
Most HIV-positive women on combination antiretroviral therapy (cART) with undetectable HIV viral load now deliver vaginally. Studies from the pre-cART era showed an association between duration of rupture of membranes (ROM) and mother-to-child transmission (MTCT). Here, we investigate the impact of ROM duration on MTCT rates in the cART era.
Thompson F, Ghanem M, Conway K, et al., 2014, Intravenous iron and vertical HIV transmission: any connection?, AIDS, Vol: 28, Pages: 1245-1246, ISSN: 0269-9370
Dimber R, Rojas JV, Guo Q, et al., 2014, Imaging brain TSPO availability with [11C]PBR28 PET in patients with retroviral ( HTLV1 and HIV-1) infection, Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), Publisher: SOC NUCLEAR MEDICINE INC, ISSN: 0161-5505
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- Citations: 1
Townsend CL, Byrne L, Cortina-Borja M, et al., 2014, Earlier initiation of ART and further decline in mother-to-child HIV transmission rates, 2000-2011, AIDS, Vol: 28, Pages: 1049-1057, ISSN: 0269-9370
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- Citations: 236
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