Imperial College London

ProfessorJonathanWeber

Faculty of MedicineDepartment of Infectious Disease

Director of the AHSC, Professor of Communicable Diseases
 
 
 
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Contact

 

+44 (0)20 7594 3905j.weber

 
 
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Assistant

 

Mrs Siobhan Pigott +44 (0)20 7594 3901

 
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Location

 

2.15Faculty BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

321 results found

Horvath A, Rogers L, Pollakis G, Baranov O, Pieroth N, Joseph S, Chachage M, Heitzer A, Maganga L, Msafiri F, Joachim A, Viegas E, Eller L-A, Kibuuka H, Rerks-Ngarm S, Pitisuttithum P, Nitayapan S, Dhitavat J, Premsri N, Fidler S, Shattock RJJ, Robb ML, Weber J, McCormack S, Munseri PJ, Lyamuya E, Nilsson C, Kroidl A, Hoelscher M, Wagner R, Geldmacher C, Held Ket al., 2023, Systematic comparison of HIV-1 Envelope-specific IgG responses induced by different vaccination regimens: Can we steer IgG recognition towards regions of viral vulnerability?, Frontiers in Immunology, Vol: 13, Pages: 1-16, ISSN: 1664-3224

Immunogens and vaccination regimens can influence patterns of immune-epitope recognition, steering them towards or away from epitopes of potential viral vulnerability. HIV-1 envelope (Env)-specific antibodies targeting variable region 2 (V2) or 3 (V3) correlated with protection during the RV144 trial, however, it was suggested that the immunodominant V3 region might divert antibody responses away from other relevant sites. We mapped IgG responses against linear Env epitopes in five clinical HIV vaccine trials, revealing a specific pattern of Env targeting for each regimen. Notable V2 responses were only induced in trials administering CRF01_AE based immunogens, but targeting of V3 was seen in all trials, with the soluble, trimeric CN54gp140 protein eliciting robust V3 recognition. Strong V3 targeting was linked to greater overall response, increased number of total recognised antigenic regions, and where present, stronger V2 recognition. Hence, strong induction of V3-specific antibodies did not negatively impact the targeting of other linear epitopes in this study, suggesting that the induction of antibodies against V3 and other regions of potential viral vulnerability need not be necessarily mutually exclusive.

Journal article

Gombe B, Streatfield C, Leal L, Opio S, Joseph S, Weber J, Hare J, Kaleebu P, Serwanga Jet al., 2022, Optimization and validation of an ELISA assay for the determination of antibody responses to CN54gp140 and AIDSVAX BE for use in the Phase IIb PrEPVacc vaccine trial, PLoS One, Vol: 17, ISSN: 1932-6203

PrEPVacc is an international, multi-centre, double-blind vaccine study comparing experimental combination vaccine regimens including DNA/AIDSVAX BE and DNA/CN54gp140 with placebo control. Simultaneously, daily oral PrEP is compared for efficacy against daily Truvada in the context of the current PrEP availability situation at the study sites. An important clinical trial outcome is the accurate measurement of in vivo antibody titer induced through vaccination. Here we report the validation of two ELISAs for CN54gp140 and AIDSVAX BE at Uganda Virus Research Institute that demonstrates precision, specificity, and robustness for assessing the reciprocal antibody end point titer in human serum. This is a critical endpoint for determining whether vaccination can provide any protection against HIV in populations at risk of acquiring HIV.

Journal article

Granger LA, Huettner I, Debeljak F, Kaleebu P, Schechter M, Tambussi G, Weber J, Miro JM, Phillips R, Babiker A, Cooper DA, Fisher M, Ramjee G, Fidler S, Frater J, Fox J, Doores KJet al., 2021, Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort, AIDS, Vol: 35, Pages: 2073-2084, ISSN: 0269-9370

Objective: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts.Design and methods: Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time.Results: In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3–4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes.Conclusion: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.

Journal article

Pelchen-Matthews A, Borges AH, Reekie J, Rasmussen LD, Wiese L, Weber J, Pradier C, Degen O, Paredes R, Tau L, Flamholc L, Gottfredsson M, Kowalska J, Jablonowska E, Mozer-Lisewska I, Radoi R, Vasylyev M, Kuznetsova A, Begovac J, Svedhem V, Clark A, Cozzi-Lepri Aet al., 2021, Prevalence and Outcomes for Heavily Treatment-Experienced Individuals Living With Human Immunodeficiency Virus in a European Cohort, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 87, Pages: 806-817, ISSN: 1525-4135

Journal article

Lévy Y, Lacabaratz C, Ellefsen-Lavoie K, Stöhr W, Lelièvre J-D, Bart P-A, Launay O, Weber J, Salzberger B, Wiedemann A, Surenaud M, Koelle DM, Wolf H, Wagner R, Rieux V, Montefiori DC, Yates NL, Tomaras GD, Gottardo R, Mayer B, Ding S, Thiébaut R, McCormack S, Chêne G, Pantaleo Get al., 2020, Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens for T cell responses requires three DNA injections. Results of the randomized multicentre EV03/ANRS VAC20 Phase I/II Trial, PLoS Pathogens, Vol: 16, ISSN: 1553-7366

DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P<0.001). In both groups, vaccine regimens induced HIV-specific polyfunctional CD4 and CD8 T cells and the production of Th1, Th2 and Th17/IL-21 cytokines. Antibody responses were also elicited in up to 81% of vaccines. A higher percentage of IgG responders was noted in the 2xDNA arm compared to the 3xDNA arm, while the 3xDNA group tended to elicit a higher magnitude of IgG3 response against specific Env antigens. We show here that the modulation of the prime strategy, without modifying the route or the dose of administration, or the combination of vectors, may influence the quality of the responses.

Journal article

Stirrup OT, Asboe D, Pozniak A, Sabin CA, Gilson R, Mackie NE, Tostevin A, Hill T, Dunn DT, UK HIV Drug Resistance Database and the UK Collaborative HIV Cohortet al., 2020, Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation, HIV Medicine, Vol: 21, Pages: 309-321, ISSN: 1464-2662

OBJECTIVES: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. METHODS: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. RESULTS: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71-0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73-1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80-1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54-0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64-1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34-1.11). CONCLUSIONS: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir.

Journal article

Kaura A, Arnold AD, Vasileios P, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, OSullivan M, Lord GM, Melikian N, Lefroy DC, Francis DP, Shah AM, Kharbanda R, Perera D, Patel RS, Mayet Jet al., 2020, Prognostic significance of troponin level in 3,121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study), Journal of the American Heart Association, Vol: 9, ISSN: 2047-9980

Background-—Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of theresult is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronaryangiography, and all-cause mortality in real-world patients presenting with AF.Methods and Results-—We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results 7 were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median followup of 1462 (interquartile range, 929–1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associatedwith a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01–1.43; P<0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9–3.4) at 250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography.The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42–0.89; P=0.01).Conclusions-—Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.

Journal article

Kaura A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah A, Channon K, Weber J, Thursz M, Elliott P, Hemingway H, Williams B, Asselbergs F, OSullivan M, Kharbanda R, Lord G, Melikian N, Patel R, Perera D, Shah A, Francis D, Mayet Jet al., 2019, Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres, BMJ-British Medical Journal, Vol: 367, ISSN: 1756-1833

ObjectiveTo determine the relation between age and troponinlevel and its prognostic implication.DesignRetrospective cohort study.SettingFive cardiovascular centres in the UK National Institutefor Health Research Health Informatics Collaborative(UK-NIHR HIC).Participants257948 consecutive patients undergoing troponintesting for any clinical reason between 2010 and2017.Main outcome measureAll cause mortality.Results257948 patients had troponin measured during thestudy period. Analyses on troponin were performedusing the peak troponin level, which was the highesttroponin level measured during the patient’s hospitalstay. Troponin levels were standardised as a multipleof each laboratory’s 99th centile of the upper limitof normal (ULN). During a median follow-up of 1198days (interquartile range 514-1866 days), 55850(21.7%) deaths occurred. A positive troponin result(that is, higher than the upper limit of normal)signified an overall 3.2-fold higher mortality hazard(95% confidence interval 3.1-fold to 3.2-fold) overthree years. The mortality hazard varied markedly withage, from 10.6-fold (8.5-fold to 13.3-fold) in 18-29year olds to 1.5 (1.4 to 1.6) in those older than 90.A positive troponin result was associated with anapproximately 15 percentage points higher absolutethree year mortality across all age groups. The excessmortality with a positive troponin result was heavilyconcentrated in the first few weeks. Results wereanalysed using multivariable adjusted restrictedcubic spline Cox regression. A direct relation wasseen between troponin level and mortality in patientswithout acute coronary syndrome (ACS, n=120049),whereas an inverted U shaped relation was foundin patients with ACS (n=14468), with a paradoxicaldecline in mortality at peak troponin levels >70xULN.In the group with ACS, the inverted U shaped relationpersisted after multivariable adjustment in those whowere managed invasively; however, a direct positiverelation was found between troponin level

Journal article

Stirrup OT, Sabin CA, Phillips AN, Williams I, Churchill D, Tostevin A, Hill T, Dunn DT, Asboe D, Pozniak A, Cane P, Chadwick D, Clark D, Collins S, Delpech V, Douthwaite S, Dunn D, Fearnhill E, Porter K, Stirrup O, Fraser C, Geretti AM, Gunson R, Hale A, Hue S, Lazarus L, Leigh-Brown A, Mbisa T, Mackie N, Orkin C, Nastouli E, Pillay D, Phillips A, Sabin C, Smit E, Templeton K, Tilston P, Volz E, Zhang H, Fairbrother K, Dawkins J, O'Shea S, Mullen J, Cox A, Tandy R, Fawcett T, Hopkins M, Booth C, Garcia-Diaz A, Renwick L, Schmid ML, Payne B, Hubb J, Dustan S, Kirk S, Bradley-Stewart A, Ainsworth J, Allan S, Anderson J, Babiker A, Gazzard B, Gilson R, Compels M, Hay P, Johnson M, Jose S, Kegg S, Leen C, Martin F, Mital D, Nelson M, Palfreeman A, Post F, Pritchard J, Schwenk A, Tariq A, Trevelion R, Ustianowski A, Walsh J, Thornton A, Huntington S, Glabay A, Shidfar S, Lynch J, Hand J, de Souza C, Perry N, Tilbury S, Youssef E, Mabika T, Mandalia S, Munshi S, Adefisan A, Taylor C, Gleisner Z, Ibrahim F, Campbell L, Baillie K, Brima N, Miller S, Wood C, Youle M, Lampe F, Smith C, Tsintas R, Chaloner C, Hutchinson S, Mackie N, Winston A, Weber J, Ramzan F, Carder M, Wilson A, Morris S, Gompels M, Allan S, Lewszuk A, Faleye A, Ogunbiyi V, Mitchell S, Kemble C, Russell-Sharpe S, Gravely J, Harte A, Spencer H, Jones R, Cumming S, Atkinson C, Edgell V, Allen J, Murphy C, Gunder Iet al., 2019, Associations between baseline characteristics, CD4 cell count response and virological failure on first-line efavirenz, Journal of virus eradication, Vol: 5, Pages: 204-211, ISSN: 2055-6640

ObjectivesThe aim of this study was to investigate associations between baseline characteristics and CD4 cell count response on first-line antiretroviral therapy and risk of virological failure (VF) with or without drug resistance.MethodsWe conducted an analysis of UK Collaborative HIV Cohort data linked to the UK HIV Drug Resistance Database. Inclusion criteria were viral sequence showing no resistance prior to initiation of first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine and virological suppression within 6 months. Outcomes of VF (≥200 copies/mL) with or without drug resistance were assessed using a competing risks approach fitted jointly with a model for CD4 cell count recovery. Hazard ratios for each VF outcome were estimated for baseline CD4 cell count and viral load and characteristics of CD4 cell count response using latent variables on a standard normal scale.ResultsA total of 3640 people were included with 338 VF events; corresponding viral sequences were available in 134 with ≥1 resistance mutation in 36. VF with resistance was associated with lower baseline CD4 (0.30, 0.09–0.62), lower CD4 recovery (0.04, 0.00–0.17) and higher CD4 variability (4.40, 1.22–12.68). A different pattern of associations was observed for VF without resistance, but the strength of these results was less consistent across sensitivity analyses. Cumulative incidence of VF with resistance was estimated to be <2% at 3 years for baseline CD4 ≥350 cells/μL.ConclusionLower baseline CD4 cell count and suboptimal CD4 recovery are associated with VF with drug resistance. People with low CD4 cell count before ART or with suboptimal CD4 recovery on treatment should be a priority for regimens with high genetic barrier to resistance.

Journal article

Neesgaard B, Pelchen-Matthews A, Ryom L, Florence E, Peters L, Roen A, Svedhem V, Clarke A, Benfield T, Mitsura V, Moreno S, Beniowski M, Begovac J, Matulionyte R, Trofimova T, Elbirt D, Kundro M, Vullo V, Behrens G, Staub T, Ragone L, Vannappagari V, Lundgren J, Mocroft A, Schmied B, Zangerle R, Karpov I, Vassilenko A, Paduto D, Clumeck N, De Wit S, Delforge M, Vandekerckhove L, Hadziosmanovic V, Machala L, Jilich D, Sedlacek D, Kronborg G, Benfield T, Gerstoft J, Katzenstein T, Pedersen C, Johansen IS, Ostergaard L, Wiese L, Moller NF, Nielsen LN, Zilmer K, Smidt J, Ristola M, Aho I, Viard J-P, Girard P-M, Pradier C, Fontas E, Duvivier C, Rockstroh J, Degen O, Stellbrink HJ, Stefan C, Bogner J, Faetkenheuer G, Chkhartishvili N, Sambatakou H, Adamis G, Paissios N, Szlavik J, Gottfredsson M, Mulcahy F, Yust I, Turner D, Burke M, Shahar E, Hassoun G, Elinav H, Haouzi M, Sthoeger ZM, Monforte AD, Esposito R, Mazeu I, Mussini C, Mazzotta F, Gabbuti A, Lichtner M, Zaccarelli M, Antinori A, Acinapura R, Plazzi M, Lazzarin A, Castagna A, Gianotti N, Galli M, Ridolfo A, Rozentale B, Uzdaviniene V, Hemmer R, Reiss P, Reikvam DH, Maeland A, Bruun J, Knysz B, Gasiorowski J, Inglot M, Bakowska E, Flisiak R, Grzeszczuk A, Parczewski M, Maciejewska K, Aksak-Was B, Mularska E, Smiatacz T, Gensing M, Jablonowska E, Kamerys J, Wojcik K, Mozer-Lisewska I, Rozplochowski B, Caldeira L, Mansinho K, Maltez F, Radoi R, Oprea C, Panteleev A, Panteleev O, Yakovlev A, Trofimora T, Khromova I, Kuzovatova E, Borodulina E, Vdoushkina E, Miro JM, Mallolas J, Martinez E, Garcia F, Blanco JL, Laguno M, Martinez-Rebollar M, del Campo S, Clotet B, Jou A, Paredes R, Puig J, Llibre JM, Santos JR, Domingo P, Gutierrez M, Mateo G, Sambeat MA, Laporte JM, Falconer K, Thalme A, Sonnerborg A, Treutiger CJ, Flamholc L, Scherrer A, Weber R, Cavassini M, Calmy A, Furrer H, Battegay M, Schmid P, Kuznetsova A, Kyselyova G, Sluzhynska M, Gazzard B, Johnson AM, Simons E, Edwards S, Phillips A, Johnson MA, Orkinet al., 2019, Uptake and effectiveness of two-drug compared with three-drug antiretroviral regimens among HIV-positive individuals in Europe, AIDS, Vol: 33, Pages: 2013-2024, ISSN: 0269-9370

Journal article

Zilber E, Martin GE, Willberg CB, Fox J, Nwokolo N, Fidler S, Frater J, CHERUB Investigatorset al., 2019, Soluble plasma programmed death 1 (PD-1) and Tim-3 in primary HIV infection., AIDS, Vol: 33, Pages: 1253-1256

: Soluble forms of the coinhibitory receptors programmed death 1 (PD-1) and Tim-3 exist, but their relationship with T-cell surface expression remains unclear. When measured by an enzyme-linked immunosorbent assay in plasma, soluble PD-1, and soluble Tim-3 were elevated during primary HIV infection, decreased on antiretroviral therapy to levels found in controls, and correlated with cell surface expression. We conclude that soluble PD-1 and soluble Tim-3 are easy to measure biomarkers of immune exhaustion which potentially eliminate the need for flow cytometry.

Journal article

Kaura A, Hartley A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs F, O'Sullivan M, Haskard D, Lord G, Melikian N, Francis D, Koenig W, Perera D, Shah A, Kharbanda R, Patel R, Mayet J, Khamis Ret al., 2019, THE ROLE OF HIGH-SENSITIVITY C-REACTIVE PROTEIN IN PREDICTING MORTALITY BEYOND TROPONIN IN OVER 100,000 PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME (NIHR HEALTH INFORMATICS COLLABORATIVE CRP-RISK STUDY), Annual Conference of the British-Cardiovascular-Society (BCS) - Digital Health Revolution, Publisher: BMJ PUBLISHING GROUP, Pages: A120-A121, ISSN: 1355-6037

Conference paper

Kaura A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs F, O'Sullivan M, Lord G, Melikian N, Kharbanda R, Shah A, Perera D, Patel R, Francis D, Mayet Jet al., 2019, THE RELATIONSHIP BETWEEN TROPONIN LEVEL AND MORTALITY IN AN UNSELECTED POPULATION OF OVER 250,000 PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME (NIHR HEALTH INFORMATICS COLLABORATIVE TROP-RISK STUDY), Annual Conference of the British-Cardiovascular-Society (BCS) - Digital Health Revolution, Publisher: BMJ PUBLISHING GROUP, Pages: A59-A59, ISSN: 1355-6037

Conference paper

Kaura A, Sterne J, Mulla A, Panoulas V, Glampson B, Davies J, Woods K, Omigie J, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs F, O'Sullivan M, Lord G, Melikian N, Francis D, Perera D, Shah A, Kharbanda R, Patel R, Mayet Jet al., 2019, INVASIVE VERSUS MEDICAL MANAGEMENT OF ELDERLY PATIENTS WITH NON-ST ELEVATION MYOCARDIAL INFARCTION (NIHR HEALTH INFORMATICS COLLABORATIVE SENIOR-NSTEMI STUDY), Annual Conference of the British-Cardiovascular-Society (BCS) - Digital Health Revolution, Publisher: BMJ PUBLISHING GROUP, Pages: A48-A49, ISSN: 1355-6037

Conference paper

Nadai Y, Held K, Joseph S, Ahmed MIM, Hoffmann VS, Peterhoff D, Missange M, Bauer A, Joachim A, Reimer U, Zerweck J, McCormack S, Cope A, Tatoud R, Shattock RJ, Robb ML, Sandstroem EG, Hoelscher M, Maboko L, Bakari M, Kroidl A, Wagner R, Weber J, Pollakis G, Geldmacher Cet al., 2019, Envelope-specific recognition patterns of HIV vaccine-induced IgG antibodies are linked to immunogen structure and sequence, Frontiers in Immunology, Vol: 10, Pages: 1-14, ISSN: 1664-3224

Background: A better understanding of the parameters influencing vaccine-induced IgG recognition of individual antigenic regions and their variants within the HIV Envelope protein (Env) can help to improve design of preventive HIV vaccines.Methods: Env-specific IgG responses were mapped in samples of the UKHVC003 Standard Group (UK003SG, n = 11 from UK) and TaMoVac01 (TMV01, n = 17 from Tanzania) HIV vaccine trials. Both trials consisted of three immunizations with DNA, followed by two boosts with recombinant Modified Vaccinia Virus Ankara (MVA), either mediating secretion of gp120 (UK003SG) or the presentation of cell membrane bound gp150 envelopes (TMV01) from infected cells, and an additional two boosts with 5 μg of CN54gp140 protein adjuvanted with glucopyranosyl lipid adjuvant (GLA). Env immunogen sequences in UK003SG were solely based on the clade C isolate CN54, whereas in TMV01 these were based on clades A, C, B, and CRF01AE. The peptide microarray included 8 globally representative Env sequences, CN54gp140 and the MVA-encoded Env immunogens from both trials, as well as additional peptide variants for hot spots of immune recognition.Results: After the second MVA boost, UK003SG vaccinees almost exclusively targeted linear, non-glycosylated antigenic regions located in the inter-gp120 interface. In contrast, TMV01 recipients most strongly targeted the V2 region and an immunodominant region in gp41. The V3 region was frequently targeted in both trials, with a higher recognition magnitude for diverse antigenic variants observed in the UK003SG (p < 0.0001). After boosting with CN54gp140/GLA, the overall response magnitude increased with a more comparable recognition pattern of antigenic regions and variants between the two trials. Recognition of most immunodominant regions within gp120 remained significantly stronger in UK003SG, whereas V2-region recognition was not boosted in either group.Conclusions: IgG recognition of linear antigenic Env regions differe

Journal article

Kaura A, Panoulas V, Glampson B, Davies J, Woods K, Mulla A, Omigie J, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Kharbanda R, Lord GM, Melikian N, Patel R, Perera D, Shah A, Francis D, Mayet Jet al., 2019, UNEXPECTED INVERTED U-SHAPED RELATIONSHIP BETWEEN TROPONIN LEVEL AND MORTALITY EXPLAINED BY REVASCULARIZATION IN BOTH PATIENTS WITH AND WITHOUT ACUTE CORONARY SYNDROME (TROP-RISK STUDY), 68th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 1086-1086, ISSN: 0735-1097

Conference paper

Kaura A, Arnold A, Panoulas V, Glampson B, Davies J, Woods K, Mulla A, Omigie J, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, Kharbanda R, Lord GM, Melikian N, Patel R, Perera D, Shah A, Lefroy D, Francis D, Mayet Jet al., 2019, CLINICAL IMPORTANCE OF TROPONIN LEVEL IN 3,121 PATIENTS PRESENTING WITH ATRIAL FIBRILLATION (AF-TROP STUDY), 68th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 410-410, ISSN: 0735-1097

Conference paper

Kaura A, Mulla A, Panoulas V, Benjamin G, Davies J, Woods K, Omigie J, Shah AD, Channon K, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Kharbanda R, Lord GM, Melikian N, Patel R, Perera D, Shah A, Francis D, Mayet Jet al., 2019, A PROPENSITY MATCHED ANALYSIS OF INVASIVE VERSUS CONSERVATIVE MANAGEMENT OF ELDERLY PATIENTS WITH NON-ST ELEVATION MYOCARDIAL INFARCTION (SENIOR-NSTEMI STUDY), 68th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 1262-1262, ISSN: 0735-1097

Conference paper

Geretti AM, White E, Orkin C, Tostevin A, Tilston P, Chadwick D, Leen C, Sabin C, Dunn DT, Asboe D, Asboe D, Pozniak A, Cane P, Chadwick D, Churchill D, Clark D, Collins S, Delpech V, Douthwaite S, Dunn D, Fearnhill E, Porter K, Tostevin A, Stirrup O, Fraser C, Gunson R, Hale A, Hue S, Lazarus L, Leigh-Brown A, Mbisa T, Mackie N, Orkin C, Nastouli E, Pillay D, Phillips A, Sabin C, Smit E, Templeton K, Tilston P, Volz E, Williams I, Zhang H, Dawkins J, O'Shea S, Mullen J, Smit E, Mbisa T, Cox A, Tandy R, Fawcett T, Hopkins M, Tilston P, Booth C, Garcia-Diaz A, Renwick L, Schmid ML, Payne B, Chadwick D, Hubb J, Dustan S, Kirk S, Gunson R, Bradley-Stewart A, Ainsworth J, Allan S, Anderson J, Babiker A, Chadwick D, Churchill D, Delpech V, Dunn D, Gazzard B, Gilson R, Gompels M, Hay P, Hill T, Johnson M, Jose S, Kegg S, Leen C, Martin F, Mital D, Nelson M, Orkin C, Palfreeman A, Phillips A, Pillay D, Post F, Pritchard J, Sabin CA, Schwenk A, Tariq A, Trevelion R, Ustianowski A, Walsh J, Hill T, Jose S, Phillips A, Sabin CA, Thornton A, Huntington S, Dunn D, Glabay A, Shidfar S, Orkin C, Lynch J, Hand J, de Souza C, Churchill D, Perry N, Tilbury S, Youssef E, Churchill D, Gazzard B, Nelson M, Mabika T, Asboe D, Mandalia S, Anderson J, Munshi S, Post F, Adefisan A, Taylor C, Gleisner Z, Ibrahim F, Campbell L, Chadwick D, Baillie K, Gilson R, Brima N, Williams I, Ainsworth J, Schwenk A, Miller S, Wood C, Johnson M, Youle M, Lampe F, Smith C, Tsintas R, Chaloner C, Hutchinson S, Sabin CA, Phillips A, Hill T, Jose S, Huntington S, Thornton A, Walsh J, Mackie N, Winston A, Weber J, Ramzan F, Carder M, Leen C, Wilson A, Morris S, Gompels M, Allan S, Palfreeman A, Lewszuk A, Kegg S, Faleye A, Ogunbiyi V, Mitchell S, Hay P, Kemble C, Martin F, Russell-Sharpe S, Gravely J, Allan S, Harte A, Tariq A, Spencer H, Jones R, Pritchard J, Cumming S, Atkinson C, Mital D, Edgell V, Allen J, Ustianowski A, Murphy C, Gunder I, Delpech V, Trevelion Ret al., 2019, Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance, Journal of Antimicrobial Chemotherapy, Vol: 74, Pages: 746-753, ISSN: 0305-7453

ObjectivesIn subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data.MethodsWe analysed 1710 subjects who started a PI/b in combination with tenofovir or abacavir plus emtricitabine or lamivudine, and compared their virological outcomes with those of 4889 patients who started an NNRTI (predominantly efavirenz), according to the presence of ≥1 TAM as the sole form of transmitted drug resistance.ResultsParticipants with ≥1 TAM comprised predominantly MSM (213 of 269, 79.2%), subjects of white ethnicity (206 of 269, 76.6%) and HIV-1 subtype B infections (234 of 269, 87.0%). Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). Over a median of 2.5 years of follow-up, 834 of 6599 (12.6%) subjects experienced viraemia (HIV-1 RNA >50 copies/mL). The adjusted HR for viraemia was 2.17 with PI/b versus NNRTI-based therapy (95% CI 1.88–2.51; P < 0.001). Other independent predictors of viraemia included injecting drug use, black ethnicity, higher viral load and lower CD4 cell count at baseline, and receiving abacavir instead of tenofovir. Resistance showed no overall impact (adjusted HR 0.77 with ≥1 TAM versus no resistance; 95% CI 0.54–1.10; P = 0.15).ConclusionsIn this cohort, patients harbouring ≥1 TAM as the sole form of transmitted drug resistance gained no apparent virological advantage from starting first-line ART with a PI/b.

Journal article

Gossez M, Martin GE, Pace M, Ramjee G, Premraj A, Kaleebu P, Rees H, Inshaw J, Stöhr W, Meyerowitz J, Hopkins E, Jones M, Hurst J, Porter K, Babiker A, Fidler S, Frater J, SPARTAC Trial Investigatorset al., 2019, Virological remission after antiretroviral therapy interruption in female African HIV seroconverters, AIDS, Vol: 33, Pages: 185-197, ISSN: 0269-9370

INTRODUCTION: There are few data on the frequency of virological remission in African individuals after treatment with antiretroviral therapy (ART) in primary HIV infection (PHI). METHODS: We studied participants (n = 82) from South Africa and Uganda in Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion, the first trial of treatment interruption in African individuals with PHI randomized to deferred ART or 48 weeks of immediate ART. All were female and infected with non-B HIV subtypes, mainly C. We measured HIV DNA in CD4 T cells, CD4 cell count, plasma viral load (pVL), cell-associated HIV RNA and T-cell activation and exhaustion. We explored associations with clinical progression and time to pVL rebound after treatment interruption (n = 22). Data were compared with non-African Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion participants. RESULTS: Pretherapy pVL and integrated HIV DNA were lower in Africans compared with non-Africans (median 4.16 vs. 4.72 log10 copies/ml and 3.07 vs. 3.61 log10 copies/million CD4 T cells, respectively; P < 0.001). Pre-ART HIV DNA in Africans was associated with clinical progression (P = 0.001, HR per log10 copies/million CD4 T cells increase (95% CI) 5.38 (1.95-14.79)) and time to pVL rebound (P = 0.034, HR per log10 copies/ml increase 4.33 (1.12-16.84)). After treatment interruption, Africans experienced longer duration of viral remission than non-Africans (P < 0.001; HR 3.90 (1.75-8.71). Five of 22 African participants (22.7%) maintained VL less than 400 copies/ml over a median of 188 weeks following treatment interruption. CONCLUSION: We find evidence of greater probability of virological remission following treatment interruption among African participants, although we are unable to differentiate between sex, ethnicity and viral subtype. The finding warrants further investigation.

Journal article

Viegas EO, Kroidl A, Munseri PJ, Missanga M, Nilsson C, Tembe N, Bauer A, Joachim A, Joseph S, Mann P, Geldmacher C, Fleck S, Stohr W, Scarlatti G, Aboud S, Bakari M, Maboko L, Hoelscher M, Wahren B, Robb ML, Weber J, McCormack S, Biberfeld G, Jani I, Sandstrom E, Lyamuya Eet al., 2018, Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design, PLoS One, Vol: 13, Pages: 1-19, ISSN: 1932-6203

BackgroundWe evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique.MethodsHealthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo.ResultsVaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p<0.001) and subtype C gp140 (24300 versus 2700, p<0.001) Env protein. At relatively low titers, neutralizing antibody responses using the TZM-bl assay were more frequent in vaccinees given adjuvanted protein boost.ConclusionIntradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significa

Journal article

Martin GE, Pace M, Thornhill JP, Phetsouphanh C, Meyerowitz J, Gossez M, Brown H, Olejniczak N, Lwanga J, Ramjee G, Kaleebu P, Porter K, Willberg CB, Klenerman P, Nwokolo N, Fox J, Fidler S, Frater Jet al., 2018, CD32-Expressing CD4 T Cells are phenotypically diverse and can contain proviral HIV DNA, Frontiers in Immunology, Vol: 9, ISSN: 1664-3224

Efforts to both characterize and eradicate the HIV reservoir have been limited by the rarity of latently infected cells and the absence of a specific denoting biomarker. CD32a (FcγRIIa) has been proposed to be a marker for an enriched CD4 T cell HIV reservoir, but this finding remains controversial. Here, we explore the expression of CD32 on CD3+CD4+ cells in participants from two primary HIV infection studies and identify at least three distinct phenotypes (CD32low, CD32+CD14+, and CD32high). Of note, CD4 negative enrichment kits remove the majority of CD4+CD32+ T cells, potentially skewing subsequent analyses if used. CD32high CD4 T cells had higher levels of HLA-DR and HIV co-receptor expression than other subsets, compatible with their being more susceptible to infection. Surprisingly, they also expressed high levels of CD20, TCRαβ, IgD, and IgM (but not IgG), markers for both T cells and naïve B cells. Compared with other populations, CD32low cells had a more differentiated memory phenotype and high levels of immune checkpoint receptors, programmed death receptor-1 (PD-1), Tim-3, and TIGIT. Within all three CD3+CD4+CD32+ phenotypes, cells could be identified in infected participants, which contained HIV DNA. CD32 expression on CD4 T cells did not correlate with HIV DNA or cell-associated HIV RNA (both surrogate measures of overall reservoir size) or predict time to rebound viremia following treatment interruption, suggesting that it is not a dominant biomarker for HIV persistence. Our data suggest that while CD32+ T cells can be infected with HIV, CD32 is not a specific marker of the reservoir although it might identify a population of HIV enriched cells in certain situations.

Journal article

Stirrup OT, Dunn DT, Tostevin A, Sabin CA, Pozniak A, Asboe D, Cox A, Orkin C, Martin F, Cane P, Fairbrother K, Fearnhill E, Hubb J, Porter K, Babiker A, Lynch J, Hand J, de Souza C, Churchill D, Perry N, Tilbury S, Youssef E, Clark D, Gazzard B, Nelson M, Mabika T, Mandalia S, Anderson J, Munshi S, Post F, Adefisan A, Taylor C, Gleisner Z, Ibrahim F, Campbell L, Chadwick D, Baillie K, Gilson R, Brima N, Williams I, Ainsworth J, Schwenk A, Miller S, Wood C, Johnson M, Youle M, Lampe F, Smith C, Tsintas R, Chaloner C, Hutchinson S, Phillips A, Hill T, Jose S, Huntington S, Thornton A, Walsh J, Mackie N, Winston A, Weber J, Ramzan F, Carder M, Leen C, Wilson A, Morris S, Gompels M, Allan S, Palfreeman A, Lewszuk A, Kegg S, Faleye A, Ogunbiyi V, Mitchell S, Hay P, Kemble C, Russell-Sharpe S, Gravely J, Allan S, Harte A, Tariq A, Spencer H, Jones R, Pritchard J, Cumming S, Atkinson C, Mital D, Edgell V, Allen J, Ustianowski A, Murphy C, Gunder Iet al., 2018, Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data, AIDS Research and Therapy, Vol: 15, ISSN: 1742-6405

Background: The prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations. Methods: We considered all data in the UK HIV Drug Resistance Database for blood samples obtained in the period 1997-2014. Where available, treatment history and patient outcomes were obtained through linkage to the UK Collaborative HIV Cohort study. A matched case-control approach was used to assess risk factors associated with the appearance of each of the mutations in ART-experienced patients, and survival analysis was used to investigate factors associated with viral suppression. A further analysis using matched controls was performed to investigate the impact of each mutation on survival. Results: A total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. The results obtained in these analyses were also consistent with potentially large associations with other drugs. Analyses were inconclusive regarding associations between the mutations and mortality, but mortality was high for pati

Journal article

quinn K, Traboni C, Dily Penchala S, bouliotis G, doyle N, libri V, Khoo S, ashby D, weber J, Nicosia A, Cortese R, Pessi A, Winston Aet al., 2017, A first-in-human study of the novel HIV-fusion inhibitor C34-PEG4-Chol., Scientific Reports, Vol: 7, ISSN: 2045-2322

Abstract:Long-acting injectable antiretroviral (LA-ARV) drugs with low toxicity profiles and propensity for drug-drug interactions are a goal for future ARV regimens. C34-PEG4-Chol is a novel cholesterol tagged LA HIV-fusion-inhibitor (FI). We assessed pre-clinical toxicology and first-in-human administration of C34-PEG4-Chol. Pre-clinical toxicology was conducted in 2 species. HIV-positive men were randomised to a single subcutaneous dose of C34-PEG4-Chol at incrementing doses or placebo. Detailed clinical (including injection site reaction (ISR) grading), plasma pharmacokinetic (time-to-minimum-effective-concentration (MEC, 25ng/mL) and pharmacodynamic (plasma HIV RNA) parameters were assessed. In both mice and dogs, no-observed-adverse effect level (NOAEL) was observed at a 12 mg/kg/dose after two weeks. Of 5 men enrolled, 3 received active drug (10mg, 10mg and 20mg). In 2 individuals grade 3 ISR occurred and the study was halted. Both ISR emerged within 12 hours of active drug dosing. No systemic toxicities were observed. The time-to-MEC was > 72 and >96 hours after 10 and 20 mg dose, respectively, and mean change in HIV RNA was -0.9 log10 copies/mL. These human pharmacodynamic and pharmacokinetic data, although limited to 3 subjects, of C34-PEG-4-Chol suggest continuing evaluation of this agent as a LA-ARV. However, alternative administration routes must be explored.

Journal article

White P, Fox J, Weber J, Ward H, Fidler Set al., 2017, HOW MUCH CAN HIV TRANSMISSION BE REDUCED IN HIGH-RISK MSM BY TARGETING TESTING TO DETECT AND TREAT PRIMARY HIV INFECTION (PHI)? ANALYSIS OF A COHORT STUDY USING AN INDIVIDUAL-BASED MODEL, P5.23 How much can hiv transmission be reduced in high-risk msm by targeting testing to detect and treat primary hiv infection (PHI)? analysis of a cohort study using an individual-based model, Publisher: BMJ PUBLISHING GROUP, Pages: A243-A244, ISSN: 1368-4973

Conference paper

Smit E, White E, Clark D, Churchill D, Zhang H, Collins S, Pillay D, Sabin C, Nelson M, Winston A, Jose S, Tostevin A, Dunn DT, UK HIV Drug Resistance Database and the UK Collaborative HIV Cohortet al., 2017, An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs., Journal of Antimicrobial Chemotherapy, Vol: 72, Pages: 2075-2082, ISSN: 1460-2091

Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis. Patients and methods: We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs. Results: Subtype B patients ( n  =   3410) were mostly MSM (78%) and those with subtype C ( n  =   810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55-2.62, P  <   0.001). Conclusions: Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. The exact clinical implications of this finding need to be further elucidated.

Journal article

Howarth AR, Burns FM, Apea V, Jose S, Hill T, Delpech VC, Evans A, Mercer CH, Michie S, Morris S, Sachikonye M, Sabin C, REACH study, UK Collaborative HIV Cohort UK CHIC studyet al., 2017, Development and application of a new measure of engagement in out-patient HIV care., HIV Med, Vol: 18, Pages: 267-274

OBJECTIVES: Commonly used measures of engagement in HIV care do not take into account that the frequency of attendance is related to changes in treatment and health status. This study developed a new measure of engagement in care (EIC) incorporating clinical factors. METHODS: We conducted semi-structured interviews with eight HIV physicians to identify factors associated with the timing of patients' next scheduled appointments. These factors informed the development of an algorithm to classify each month of follow-up as "in care" (on or before the time of the next expected attendance) or "out of care" (after the time of the next expected attendance). The EIC algorithm was applied to data from the UK Collaborative HIV Cohort (UK CHIC) study, a large clinical cohort study. RESULTS: The interviews indicated that time to next appointment varied depending on psychosocial and physical comorbidities, and clinical factors (time since diagnosis, AIDS diagnosis, treatment status, CD4 count and viral load). The resulting EIC algorithm was applied to 44 432 patients; 83.9% of the 3 021 224 person-months were "in care". Greater EIC was independently associated with older age, white ethnicity, HIV acquisition through sex between men, current use of antiretroviral therapy (ART), a higher nadir CD4 count, later calendar year and being seen at the clinic for the first time within the last year. CONCLUSIONS: This algorithm describing engagement in HIV care incorporates a time-updated measure of patients' treatment and health status. It adds to the options available for measuring this key performance indicator.

Journal article

Joseph S, Quinn K, Greenwood A, Cope A, McKay P, Hayes P, Kopycinski J, Gilmour J, Miller A, Geldmacher C, Nadai Y, Ahmed M, Montefiori D, Dally L, Bouliotis G, Lewis D, Tatoud R, Wagner R, Esteban M, Shattock R, McCormack S, Weber Jet al., 2017, A comparative phase I study of combination, homologous subtype-C DNA, MVA, and Env gp140 protein/adjuvant HIV vaccines in two immunization regimes, Frontiers in Immunology, Vol: 8, ISSN: 1664-3224

There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% individuals after boosting with gp140 and that combined vaccines would not compromise safety and might augment immunogenicity. Forty volunteers were primed three times with DNA plasmids encoding (CN54) env and (ZM96) gag-pol-nef at 0, 4 and 8 weeks then boosted with MVA-C (CN54 env and gag-pol-nef) and glucopyranosyl lipid adjuvant—aqueous formulation (GLA-AF) adjuvanted CN54gp140. They were randomised to receive them in combination at the same visit at 16 and 20 weeks (accelerated) or sequentially with MVA-C at 16, 20, and GLA-AF/gp140 at 24 and 28 weeks (standard). All vaccinations were intramuscular. Primary outcomes included ≥grade 3 safety events and the titer of CN54gp140-specific binding IgG. Other outcomes included neutralization, binding antibody specificity and T-cell responses. Two participants experienced asymptomatic ≥grade 3 transaminitis leading to discontinuation of vaccinations, and three had grade 3 solicited local or systemic reactions. A total of 100% made anti-CN54gp140 IgG and combining vaccines did not significantly alter the response; geometric mean titer 6424 (accelerated) and 6578 (standard); neutralization of MW965.2 Tier 1 pseudovirus was superior in the standard group (82 versus 45% responders, p = 0.04). T-cell ELISpot responses were CD4+ and Env-dominant; 85 and 82% responding in the accelerated and standard groups, respectively. Vaccine-induced IgG responses targeted multiple regions within gp120 with the V3 region most immunodominant and no differences between groups detected. Combining MVA and gp140 vaccines did not result in increased adverse events and did not significantly impact upon the titer of Env-specific binding antibodies, which were seen in 100% individuals. The ap

Journal article

Shepherd L, Borges A, Harvey R, Bower M, Grulich A, Silverberg M, Weber J, Ristola M, Viard J-P, Bogner J, Gargalianos-Kakolyri P, Mussini C, Mansinho K, Yust I, Calmy A, Paduta D, Jilich D, Smiatacz T, Radoi R, Tomazic J, Plomgaard P, Frikke-Schmidt R, Lundgren J, Mocroft Aet al., 2016, The extent of B-cell activation and dysfunction preceding lymphoma development, Journal of the International AIDS Society, Vol: 19, Pages: 143-144, ISSN: 1758-2652

Journal article

Nadai Y, Ahmed MIM, Joseph S, Missanga M, Bauer A, Cope AV, Joachim A, Reimer U, Pollakis G, McCormack S, Tatoud R, Shattock RJ, Robb M, Sandstroem E, Hoelscher M, Bakari M, Maboko L, Kroidl A, Weber J, Geldmacher C, Held Ket al., 2016, Env-specific IgG Responses Induced by Identical and None-identical Immunogen Prime-boost Vaccination Strategies Target Different Antigenic Regions, Conference on HIV Research for Prevention (HIV R4P), Publisher: MARY ANN LIEBERT, INC, Pages: 392-392, ISSN: 0889-2229

Conference paper

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