Publications
518 results found
Mulligan N, Schalkwijk S, Best BM, et al., 2016, Etravirine Pharmacokinetics in HIV-Infected Pregnant Women, Frontiers in Pharmacology, Vol: 7, ISSN: 1663-9812
BACKGROUND: The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women. METHODS: IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL). RESULTS: Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0-12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19-4.25) and no perinatal transmission occurred. CONCLUSION: Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available. CLINICAL TRIAL REGISTRATION: The IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929.
Adonis A, Taylor GP, 2016, Assessing Walking Ability in People with HTLV-1-Associated Myelopathy Using the 10 Meter Timed Walk and the 6 Minute Walk Test, PLOS One, Vol: 11, ISSN: 1932-6203
Phillips AA, Fields P, Hermine O, et al., 2016, A prospective, multicenter, randomized study of anti-CCR4 monoclonal antibody mogamulizumab (moga) vs investigator's choice (IC) in the treatment of patients (pts) with relapsed/refractory (R/R) adult T-cell leukemia-lymphoma (ATL), Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
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- Citations: 9
Phillips AA, Horwitz SM, Taylor GP, et al., 2016, Differences between Japan and rest of world (ROW) in disease presentation and outcome of previously treated adult t-cell leukemia-lymphoma (ATL) using therapy with a monoclonal antibody to CCR4, mogamulizumab (moga)., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Schalkwijk S, Colbers A, Konopnicki D, et al., 2016, The pharmacokinetics of abacavir 600 mg once daily in HIV-1-positive pregnant women, AIDS, Vol: 30, Pages: 1239-1244, ISSN: 0269-9370
Objective: To describe the pharmacokinetics of abacavir 600 mg once daily (q.d.) in HIV-1-positive women during pregnancy and postpartum.Design: A nonrandomized, open-label, multicentre, phase-IV study.Methods: HIV-positive pregnant women receiving abacavir 600 mg q.d. as part of clinical care were included. Intensive 24-h pharmacokinetic sampling was performed during the third trimester and at least 2 weeks after delivery. Pharmacokinetic parameters were calculated by noncompartmental analysis. Paired cord blood and maternal blood samples were taken at delivery when feasible.Results: A total of 14 women were included in the analysis. Geometric mean ratios (90% confidence intervals) of third trimester versus postpartum were 1.05 (0.92–1.19) for AUC0–24h and 1.00 (0.83–1.21) for Cmax. The median (range) ratio of abacavir cord plasma to maternal plasma was 1.0 (0.7–1.0, n = 3). Viral load at the third trimester visit was less than 50 copies/ml in 13 participants (93%; one unknown). In total, 13 (93%; one unknown) children were tested HIV-negative.Conclusion: The pharmacokinetics of abacavir 600 mg q.d. during pregnancy are equivalent to postpartum. No dose adjustments are required during pregnancy and similar antiviral activity is expected.
Manivannan K, Rowan AG, Tanaka Y, et al., 2016, CADM1/TSLC1 identifies HTLV-1-infected cells and determines their susceptibility to CTL-mediated lysis, PLOS Pathogens, Vol: 12, ISSN: 1553-7366
Human T cell lymphotropic virus-1 (HTLV-1) primarily infects CD4+ T cells, causing inflammatory disorders or a T cell malignancy in 5% to 10% of carriers. The cytotoxic T lymphocyte (CTL) response is a key factor that controls the viral load and thus the risk of disease. The ability to detect the viral protein Tax in primary cells has made it possible to estimate the rate at which Tax-expressing infected cells are eliminated by CTLs in persistently infected people. However, most HTLV-1-infected cells are Tax–at a given time, and their immunophenotype is poorly defined. Here, we aimed to identify a cell-surface molecule expressed by both Tax+ and Tax–HTLV-1-infected cells and use it to analyse the CTL response in fresh peripheral blood mononuclear cells. Cell adhesion molecule 1 (CADM1/TSLC1) was the best single marker of HTLV-1 infection, identifying HTLV-1-infected cells with greater sensitivity and specificity than CD25, CCR4 or ICAM-1. CADM1+CD4+ T cells carried a median of 65% of proviral copies in peripheral blood. In a cohort of 23 individuals, we quantified the rate of CTL-mediated killing of Tax+ and Tax−CADM1+ cells. We show that CADM1 expression is associated with enhanced susceptibility of infected cells to CTL lysis: despite the immunodominance of Tax in the CTL response, Tax+CADM1– cells were inefficiently lysed by CTLs. Upregulation of the CADM1 ligand CRTAM on CD8+ T cells correlated with efficient lysis of infected cells. Tax–CADM1+ cells were lysed at a very low rate by autologous CTLs, however, were efficiently killed when loaded with exogenous peptide antigen. High expression of CADM1 on most HTLV-1-infected cells in the face of enhanced CTL counterselection implies that CADM1 confers a strong benefit on the virus.
Buell KG, Puri A, Demontis MA, et al., 2016, Effect of pulsed methylprednisolone on pain, in patients with HTLV-1-associated myelopathy, PLOS One, Vol: 11, ISSN: 1932-6203
Sornum A, Owen L, Brown CS, et al., 2016, A retrospective review of admissions - what can we learn?, HIV Medicine, Vol: 17, Pages: 59-59, ISSN: 1464-2662
Fox JM, Hilburn S, Demontis MA, et al., 2016, Long terminal repeat circular DNA as markers of active viral replication of human T lymphotropic virus-1 in vivo, Viruses, Vol: 8, ISSN: 1999-4915
Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1) infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1), HTLV-1 plasma RNA is sparse. The contribution of the "mitotic" spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR) DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT) usage and infectious activity. 1LTR and 2LTR DNA circles were measured in HTLV-1 cell lines and peripheral blood mononuclear cells (PBMC) of asymptomatic carriers (ACs) and patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukaemia/lymphoma (ATLL). 1LTR DNA circles were detected in 14/20 patients at a mean of 1.38/100 PBMC but did not differentiate disease status nor correlate with HTLV-1 DNA copies. 2LTR DNA circles were detected in 30/31 patients and at higher concentrations in patients with HTLV-1-associated diseases, independent of HTLV-1 DNA load. In an incident case the 2LTR DNA circle concentration increased 2.1 fold at the onset of HAM/TSP compared to baseline. Detectable and fluctuating levels of HTLV-1 DNA circles in patients indicate viral RT usage and virus replication. Our results indicate HTLV-1 viral replication capacity is maintained in chronic infection and may be associated with disease onset.
Fox JM, Mutalima N, Molyneux E, et al., 2016, Seroprevalence of HTLV-1 and HTLV-2 amongst mothers and children in Malawi within the context of a systematic review and meta-analysis of HTLV seroprevalence in Africa, Tropical Medicine & International Health, Vol: 21, Pages: 312-324, ISSN: 1365-3156
ObjectivesHuman T-lymphotropic virus (HTLV)-1 causes T-cell leukaemia and myelopathy. Together with HTLV-2, it is endemic in some African nations. Seroprevalence data from Malawi are scarce, with no reports on associated disease incidence. HTLV seroprevalence and type were tested in 418 healthy mothers from Malawi. In addition, we tested the sera of 534 children to investigate mother-to-child transmission. To provide context, we conducted a systematic review and meta-analysis of HTLV seroprevalence in African women and children.MethodsStored samples from a previous childhood cancer and BBV study were analysed. ELISA was used for HTLV screening followed by immunoblot for confirmation and typing. Standard methods were used for the systematic review.ResultsHTLV seroprevalence was 2.6% (11/418) in mothers and 2.2% (12/534) in children. Three mothers carried HTLV-1 alone, seven had HTLV-2 and one was dually infected. Three children carried HTLV-1 alone, seven had HTLV-2 and two were dually infected. Only two corresponding mothers of the 12 HTLV-positive children were HTLV positive. The systematic review included 66 studies of women and 13 of children conducted in 25 African countries. Seroprevalence of HTLV-1 varied from 0 to 17% and of HTLV-2 from 0 to 4%.ConclusionsIn contrast to findings from other studies in Africa, the seroprevalence of HTLV-2 was higher than that of HTLV-1 in Malawi and one of the highest for the African region. The lack of mother–child concordance suggests alternative sources of infection among children. Our data and analyses contribute to HTLV prevalence mapping in Africa.
Pollock KM, Montamat-Sicotte D, Grass L, et al., 2016, PD-1 expression and cytokine secretion profiles of Mycobacterium tuberculosis-specific CD4+ T-cell subsets; potential correlates of containment in HIV-TB co-infection, PLOS One, Vol: 11, ISSN: 1932-6203
HIV co-infection is an important risk factor for tuberculosis (TB) providing a powerful model in which to dissect out defective, protective and dysfunctional Mycobacterium tuberculosis (MTB)-specific immune responses. To identify the changes induced by HIV co-infection we compared MTB-specific CD4+ responses in subjects with active TB and latent TB infection (LTBI), with and without HIV co-infection. CD4+ T-cell subsets producing interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α) and expressing CD279 (PD-1) were measured using polychromatic flow-cytometry. HIV-TB co-infection was consistently and independently associated with a reduced frequency of CD4+ IFN-γ and IL-2-dual secreting T-cells and the proportion correlated inversely with HIV viral load (VL). The impact of HIV co-infection on this key MTB-specific T-cell subset identifies them as a potential correlate of mycobacterial immune containment. The percentage of MTB-specific IFN-γ-secreting T-cell subsets that expressed PD-1 was increased in active TB with HIV co-infection and correlated with VL. This identifies a novel correlate of dysregulated immunity to MTB, which may in part explain the paucity of inflammatory response in the face of mycobacterial dissemination that characterizes active TB with HIV co-infection.
Cook LBM, Melamed A, Demontis MA, et al., 2016, Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients, Retrovirology, Vol: 13, ISSN: 1742-4690
BackgroundHuman T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million persons globally with transmission resulting in lifelong infection. Disease, linked to high proviral load, occurs in a minority. In established infection HTLV-1 replicates through infectious spread and clonal expansion of infected lymphocytes. Little is known about acute HTLV-1 infection. The kinetics of early HTLV-1 infection, following transplantation-acquired infection in three recipients from one HTLV-1 infected donor, is reported. The recipients were treated with two HTLV-1 enzyme inhibitors 3 weeks post exposure following the detection of HTLV-1 provirus at low level in each recipient. HTLV-1 infection was serially monitored by serology, quantification of proviral load and HTLV-1 2LTR DNA circles and by HTLV-1 unique integration site analysis.ResultsHTLV-1 antibodies were first detected 16–39 days post-transplantation. HTLV-1 provirus was detected by PCR on day 16–23 and increased by 2–3 log by day 38–45 with a peak proviral doubling time of 1.4 days, after which steady state was reached. The rapid proviral load expansion was associated with high frequency of HTLV-1 2LTR DNA circles. The number of HTLV-1 unique integration sites was high compared with established HTLV-1 infection. Clonal expansion of infected cells was detected as early as day 37 with high initial oligoclonality index, consistent with early mitotic proliferation.ConclusionsIn recipients infected through organ transplantation HTLV-1 disseminated rapidly despite early anti-HTLV-1 treatment. Proviral load set point was reached within 6 weeks. Seroconversion was not delayed. Unique integration site analysis and HTLV-1 2LTR DNA circles indicated early clonal expansion and high rate of infectious spread.
Salem AH, Jones AK, Santini-Oliveira M, et al., 2015, No need for lopinavir dose adjustment during pregnancy: a population pharmacokinetic and exposure-response analysis in pregnant and nonpregnant HIV-infected subjects, Antimicrobial Agents and Chemotherapy, Vol: 60, Pages: 400-408, ISSN: 1098-6596
Lopinavir-ritonavir is frequently prescribed to HIV-1-infected women during pregnancy. Decreased lopinavir exposure has been reported during pregnancy, but the clinical significance of this reduction is uncertain. This analysis aimed to evaluate the need for lopinavir dose adjustment during pregnancy. We conducted a population pharmacokinetic analysis of lopinavir and ritonavir concentrations collected from 84 pregnant and 595 nonpregnant treatment-naive and -experienced HIV-1-infected subjects enrolled in six clinical studies. Lopinavir-ritonavir doses in the studies ranged between 400/100 and 600/150 mg twice daily. In addition, linear mixed-effect analysis was used to compare the area under the concentration-time curve from 0 to 12 h (AUC0–12) and concentration prior to dosing (Cpredose) in pregnant women and nonpregnant subjects. The relationship between lopinavir exposure and virologic suppression in pregnant women and nonpregnant subjects was evaluated. Population pharmacokinetic analysis estimated 17% higher lopinavir clearance in pregnant women than in nonpregnant subjects. Lopinavir clearance values postpartum were 26.4% and 37.1% lower than in nonpregnant subjects and pregnant women, respectively. As the tablet formulation was estimated to be 20% more bioavailable than the capsule formulation, no statistically significant differences between lopinavir exposure in pregnant women receiving the tablet formulation and nonpregnant subjects receiving the capsule formulation were identified. In the range of lopinavir AUC0–12 or Cpredose values observed in the third trimester, there was no correlation between lopinavir exposure and viral load or proportion of subjects with virologic suppression. Similar efficacy was observed between pregnant women and nonpregnant subjects receiving lopinavir-ritonavir at 400/100 mg twice daily. The pharmacokinetic and pharmacodynamic results support the use of a lopinavir-ritonavir 400/100-mg twice-daily dose during pr
Dillon R, Cook L, Saxena A, et al., 2015, Whole Exome Sequencing of Flow Purified Tumour Cells Reveals Recurrently Mutated Genes and Pathways in Adult T-Cell Lymphoma/Leukaemia (ATLL), 57th Annual Meeting of the American-Society-of-Hematology, Publisher: American Society of Hematology, ISSN: 0006-4971
Rockwood N, Cook L, Kagdi H, et al., 2015, Immune compromise in HIV-1/HTLV-1 coinfection with paradoxical resolution of CD4 lymphocytosis during antiretroviral therapy: a case report, Medicine, Vol: 94, ISSN: 0304-5412
Abstract: Human immunodeficiency virus type-1 (HIV-1) and human T lymphotropic virus type-1 (HTLV-1) infections have complex effects on adaptive immunity, with specific tropism for, but contrasting effects on, CD4 T lymphocytes: depletion with HIV-1, proliferation with HTLV-1. Impaired T lymphocyte function occurs early in HIV-1 infection but opportunistic infections (OIs) rarely occur in the absence of CD4 lymphopenia. In the unusual case where a HIV-1 infected individual with a high CD4 count presents with recurrent OIs, a clinician is faced with the possibility of a second underlying comorbidity.We present a case of pseudo-adult T cell leukemia/lymphoma (ATLL) in HIV-1/HTLV-1 coinfection where the individual fulfilled Shimoyama criteria for chronic ATLL and had pulmonary Mycobacterium kansasii, despite a high CD4 lymphocyte count. However, there was no evidence of clonal T-cell proliferation by T-cell receptor gene rearrangement studies nor of monoclonal HTLV-1 integration by high-throughput sequencing. Mutually beneficial interplay between HIV-1 and HTLV-1, maintaining high level HIV-1 and HTLV-1 viremia and proliferation of poorly functional CD4 cells despite chronicity of infection is a postulated mechanism.Despite good microbiological response to antimycobacterial therapy, the patient remained systemically unwell with refractory anemia. Subsequent initiation of combined antiretroviral therapy led to paradoxical resolution of CD4 T lymphocytosis as well as HIV-1 viral suppression and decreased HTLV-1 proviral load. This is proposed to be the result of attenuation of immune activation post-HIV virological control.This case illustrates the importance of screening for HTLV-1 in HIV-1 patients with appropriate clinical presentation and epidemiological risk factors and explores mechanisms for the complex interactions on HIV-1/HTLV-1 adaptive immunity.
Cook LB, Taylor GP, 2015, Treatment of adult T-cell leukaemia/lymphoma: is the virus a target?, CURRENT OPINION IN INFECTIOUS DISEASES, Vol: 28, Pages: 583-588, ISSN: 0951-7375
Huntington S, Thorne C, Newell M-L, et al., 2015, The risk of viral rebound in the year after delivery in women remaining on antiretroviral therapy, AIDS, Vol: 29, Pages: 2269-2278, ISSN: 0269-9370
Objective: The objective of this study is to assess the risk of viral rebound in postpartum women on suppressive combination antiretroviral therapy (cART).Methods: Using data from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC), women with HIV-RNA 50 copies/ml or less at delivery in 2006–2011, who started life-long cART during pregnancy (n = 321) or conceived on cART (n = 618), were matched by age, duration on cART and time period, with at least one control (non-postpartum). The cumulative probability of viral rebound (HIV-RNA >200 copies/ml) was assessed by Kaplan–Meier analysis; adjusted hazard ratios (aHRs) for the 0–3 and 3–12 months postdelivery (cases)/pseudo-delivery (controls) were calculated in Cox proportional hazards models.Results: In postpartum women who conceived on cART, 5.9% [95% confidence interval (95% CI) 4.0–7.7] experienced viral rebound by 3 months, and 2.2% (1.4–3.0%) of their controls. The risk of viral rebound was higher in postpartum women than in controls during the first 3 months [aHR 2.63 (1.58–4.39)] but not during the 3–12 months postdelivery/pseudo-delivery. In postpartum women who started cART during pregnancy, 27% (22–32%) experienced viral rebound by 3 months, and 3.0% (1.6–4.4%) of their controls. The risk of viral rebound was higher in postpartum women than in controls during both postdelivery/pseudo-delivery periods [<3 months: aHR 6.63 (3.58–12.29); 3–12 months: aHR 4.05 (2.03–8.09)].Conclusion: In women on suppressive cART, the risk of viral rebound is increased following delivery, especially in the first 3 months, which may be related to reduced adherence, indicating the need for additional adherence support for postpartum women.
Colbers A, Best B, Schalkwijk S, et al., 2015, Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women, CLINICAL INFECTIOUS DISEASES, Vol: 61, Pages: 1582-1589, ISSN: 1058-4838
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Bangham CRM, Melamed A, Laydon D, et al., 2015, HTLV-1 drives vigorous clonal expansion of infected CD8 + T cells in natural infection, Retrovirology, Vol: 12, ISSN: 1742-4690
BackgroundHuman T-lymphotropic Virus Type I (HTLV-1) is a retrovirus that persistently infects 5–10 million individuals worldwide and causes disabling or fatal inflammatory and malignant diseases. The majority of the HTLV-1 proviral load is found in CD4 + T cells, and the phenotype of adult T cell leukemia (ATL) is typically CD4 + . HTLV-1 also infects CD8 + cells in vivo, but the relative abundance and clonal composition of the two infected subpopulations have not been studied. We used a high-throughput DNA sequencing protocol to map and quantify HTLV-1 proviral integration sites in separated populations of CD4 + cells, CD8 + cells and unsorted peripheral blood mononuclear cells from 12 HTLV-1-infected individuals.ResultsWe show that the infected CD8 + cells constitute a median of 5 % of the HTLV-1 proviral load. However, HTLV-1-infected CD8 + clones undergo much greater oligoclonal proliferation than the infected CD4 + clones in infected individuals, regardless of disease manifestation. The CD8 + clones are over-represented among the most abundant clones in the blood and are redetected even after several years.ConclusionsWe conclude that although they make up only 5 % of the proviral load, the HTLV-1-infected CD8 + T-cells make a major impact on the clonal composition of HTLV-1-infected cells in the blood. The greater degree of oligoclonal expansion observed in the infected CD8 + T cells, contrasts with the CD4 + phenotype of ATL; cases of CD8 + adult T-cell leukaemia/lymphoma are rare. This work is consistent with growing evidence that oligoclonal expansion of HTLV-1-infected cells is not sufficient for malignant transformation.
Blonk MI, Colbers APH, Hidalgo-Tenorio C, et al., 2015, Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy, CLINICAL INFECTIOUS DISEASES, Vol: 61, Pages: 809-816, ISSN: 1058-4838
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- Citations: 48
Phillips A, Fields P, Hermine O, et al., 2015, Anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) or investigator's choice in subjects with relapsed or refractory adult T-cell leukemia-lymphoma (ATL), RETROVIROLOGY, Vol: 12, ISSN: 1742-4690
Taylor GP, Cook L, Haddow J, 2015, Baseline CD8 T-cell activation is not associated with survival in ATLL, RETROVIROLOGY, Vol: 12, ISSN: 1742-4690
Buell K, Puri A, Demontis MA, et al., 2015, Effect of pulsed methylprednisolone on disease severity, viral load and inflammation in patients with human T-lymphotropic virus type 1 associated myelopathy, RETROVIROLOGY, Vol: 12, ISSN: 1742-4690
Adonis A, Taylor GP, 2015, Comparison of walking measures in patients with HTLV-1 Associated Myelopathy, RETROVIROLOGY, Vol: 12, ISSN: 1742-4690
Desrames A, Cassar O, Gout O, et al., 2015, Northern African strains of human T-lymphotropic virus type 1 arose from a recombination event, RETROVIROLOGY, Vol: 12, ISSN: 1742-4690
Kagdi H, Rowan A, Demontis MA, et al., 2015, Molecular characterization of heterogeneity in adult T-cell leukaemia/lymphoma, Publisher: BioMed Central, ISSN: 1742-4690
Manivannan K, Rowan AG, Taylor GP, et al., 2015, Tumor suppressor in lung cancer identifies latency infected cells in non malignant HTLV-1 infection, Publisher: BIOMED CENTRAL LTD, ISSN: 1742-4690
Rowan AG, Fields P, Taylor GP, et al., 2015, T-cell receptor chain Vbeta subunit staining to quantify the malignant clone in adult T-cell leukemia, Publisher: BIOMED CENTRAL LTD, ISSN: 1742-4690
Kagdi H, Rowan A, Child F, et al., 2015, CD8 malignant proliferation in association with human T cell lymphotropic Virus 1 infection: a case report, 17th International Conference on Human Retroviruses: HTLV and Related Viruses, Publisher: BioMed Central, Pages: P68-P68, ISSN: 1742-4690
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
Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the CNS that causes weakness or paralysis of the legs, lower back pain and urinary symptoms. HAM/TSP was first described in Jamaica in the nineteenth century, but the aetiology of the condition, infection with the retrovirus HTLV-1, was only identified in the 1980s. HAM/TSP causes chronic disability and, accordingly, imposes a substantial health burden in areas where HTLV-1 infection is endemic. Since the discovery of the cause of HAM/TSP, considerable advances have been made in the understanding of the virology, immunology, cell biology and pathology of HTLV-1 infection and its associated diseases. However, progress has been limited by the lack of accurate animal models of the disease. Moreover, the treatment of HAM/TSP remains highly unsatisfactory: antiretroviral drugs have little impact on the infection and, although potential disease-modifying therapies are widely used, their value is unproved. At present, clinical management is focused on symptomatic treatment and counselling. Here, we summarize current knowledge on the epidemiology, pathogenesis and treatment of HAM/TSP and identify areas in which further research is needed.
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