Imperial College London

ProfessorAlanWinston-OKeefe

Faculty of MedicineDepartment of Infectious Disease

Professor of Genito-Urinary Medicine
 
 
 
//

Contact

 

+44 (0)20 3312 1603a.winston

 
 
//

Location

 

Winston Churchill WingSt Mary's Campus

//

Summary

 

Publications

Publication Type
Year
to

174 results found

Asad H, Collins IJ, Goodall RL, Crichton S, Hill T, Doerholt K, Foster C, Lyall H, Post FA, Welch S, Winston A, Sabin CA, Judd A, Collaborative HIV Paediatric Study CHIPS Steering Committee, the UK Collaborative HIV Cohort UK CHIC Study Steering Committeeet al., 2021, Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK., HIV Med, Vol: 22, Pages: 631-640

OBJECTIVES: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. METHODS: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. RESULTS: At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/μL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/μL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. CONCLUSIONS: Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality.

Journal article

Frater J, Ewer KJ, Ogbe A, Pace M, Adele S, Adland E, Alagaratnam J, Aley PK, Ali M, Ansari MA, Bara A, Bittaye M, Broadhead S, Brown A, Brown H, Cappuccini F, Cooney E, Dejnirattisai W, Dold C, Fairhead C, Fok H, Folegatti PM, Fowler J, Gibbs C, Goodman AL, Jenkin D, Jones M, Makinson R, Marchevsky NG, Mujadidi YF, Nguyen H, Parolini L, Petersen C, Plested E, Pollock KM, Ramasamy MN, Rhead S, Robinson H, Robinson N, Rongkard P, Ryan F, Serrano S, Tipoe T, Voysey M, Waters A, Zacharopoulou P, Barnes E, Dunachie S, Goulder P, Klenerman P, Screaton GR, Winston A, Hill AVS, Gilbert SC, Pollard AJ, Fidler S, Fox J, Lambe T, Watson MEE, Song R, Cicconi P, Minassian AM, Bibi S, Kerridge S, Singh N, Green CM, Douglas AD, Lawrie AM, Clutterbuck EAet al., 2021, Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial, The Lancet HIV, Vol: 8, Pages: e474-e485, ISSN: 2352-3018

BackgroundData on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV.MethodsIn this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18–55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per μL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4–6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing.FindingsBetween Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2–49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per μL (IQR 573·5–859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime va

Journal article

De Francesco D, Wang X, Dickinson L, Underwood J, Bagkeris E, Babalis DS, Mallon PWG, Post FA, Vera JH, Sachikonye M, Williams I, Khoo S, Sabin CA, Winston A, Boffito Met al., 2021, Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV, PLOS ONE, Vol: 16, ISSN: 1932-6203

Journal article

Nelson M, Winston A, Hill A, Mngqibisa R, Bassa A, Orkin C, Rassool M, Rodgers A, Teal V, Kumar S, Teppler Het al., 2021, Efficacy, safety and central nervous system effects after switch from efavirenz/tenofovir/emtricitabine to doravirine/tenofovir/lamivudine, AIDS, Vol: 35, Pages: 759-767, ISSN: 0269-9370

Journal article

Beanland A, Alagaratnam J, Goffe C, Bailey A, Dosekun O, Petersen C, Ayap W, Garvey LJ, Walsh J, Mackie NE, Winston Aet al., 2021, Objective and subjective rapid frailty screening tools in people with HIV, HIV Medicine, Vol: 22, Pages: 146-150, ISSN: 1464-2662

OBJECTIVES: As people with HIV (PWH) age, the prevalence of frailty increases. Rapid screening tests to identify frailty within HIV outpatient settings are required to identify at-risk individuals. We undertook a service evaluation to assess three short frailty assessments in PWH. METHODS: We assessed two objective [gait speed (GS), timed-up-and-go test (TUGT)] and one subjective [the self-reported health questionnaire (SRH)] frailty screening tools in PWH aged > 40 years attending a single HIV outpatient department. Factors associated with positive frailty screening tests (defined as GS < 0.8 m/s, TUGT ≥ 10 s and SRH score < 6) were assessed using logistic regression models. ETHICAL CONSIDERATIONS: This was a service evaluation and was approved as a service evaluation by the Imperial College Healthcare NHS trust HIV clinical research committee (February 2020). All participants were given verbal information and were able to terminate the screening tests at any time. RESULTS: Of 84 PWH approached, 80 individuals completed all screening tests (median age = 56 years, range: 40-80) with a positive frailty screening prevalence in 19%, 33% and 20% for GS, TUGT and SRH, respectively. All tests were considered acceptable to participants. Factors statistically significantly associated with frailty included age (GS and TUGT), detectable HIV RNA (TUGT), number of comorbidities (GS and TUGT), presence of polypharmacy (GS and TUGT) and total number of concomitant medication (GS and SRH). CONCLUSIONS: Rates of positive screening tests for frailty are dependent on screening tool used, with all three tools being acceptable to participants. Objective measures of frailty screening (GS and TUGT) are more closely associated with clinical parameters than is a subjective measure of frailty screening (SRH).

Journal article

De Francesco D, Underwood J, Anderson J, Boffito M, Post FA, Sachikonye M, Mallon PWG, Haddow L, Vera JH, Kunisaki KM, Sabin CA, Winston Aet al., 2020, Correlation between computerised and standard cognitive testing in people with HIV and HIV-negative individuals, AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV, ISSN: 0954-0121

Journal article

Ryom L, Cotter A, De Miguel R, B├ęguelin C, Podlekareva D, Arribas JR, Marzolini C, Mallon P, Rauch A, Kirk O, Molina JM, Guaraldi G, Winston A, Bhagani S, Cinque P, Kowalska JD, Collins S, Battegay M, EACS Governing Boardet al., 2020, 2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0, HIV Medicine, Vol: 21, Pages: 617-624, ISSN: 1464-2662

BACKGROUND: The European AIDS Clinical Society (EACS) Guidelines cover key aspects of HIV management with major updates every two years. GUIDELINE HIGHLIGHTS: The 2019 Guidelines were extended with a new section focusing on drug-drug interactions and other prescribing issues in people living with HIV (PLWH). The recommendations for treatment-naïve PLWH were updated with four preferred regimens favouring unboosted integrase inhibitors. A two-drug regimen with dolutegravir and lamivudine, and a three-drug regimen including doravirine were also added to the recommended initial regimens. Lower thresholds for hypertension were expanded to all PLWH and for cardiovascular disease prevention, the 10-year predicted risk threshold for consideration of antiretroviral therapy (ART) modification was lowered from 20% to 10%. Frailty and obesity were added as new topics. It was specified to use urine albumin to creatinine ratio to screen for glomerular disease and urine protein to creatinine ratio for tubular diseases, and thresholds were streamlined with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Hepatitis C virus (HCV) treatment recommendations were split into preferred and alternative treatment options. The algorithm for management of recently acquired HCV infection was updated and includes recommendations for early chronic infection management. Treatment of resistant tuberculosis (TB) was streamlined with the World Health Organization (WHO) recommendations, and new tables on immune reconstitution inflammatory syndrome, on when to start ART in the presence of opportunistic infections and on TB drug dosing were included. CONCLUSIONS: The EACS Guidelines underwent major revisions of all sections in 2019. They are available in four different formats including a new interactive web-based version and are translated into Chinese, French, German, Japanese, Portuguese, Russian and Spanish.

Journal article

Toniolo S, Cercignani M, Mora-Peris B, Underwood J, Alagaratnam J, Bozzali M, Boffito M, Nelson M, Winston A, Vera JHet al., 2020, Changes in functional connectivity in people with HIV switching antiretroviral therapy, Journal of NeuroVirology, Vol: 26, Pages: 754-763, ISSN: 1355-0284

We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with HIV (PWH) switching combination antiretroviral therapy (cART). In a prospective study (baseline and follow-up after at least 4 months), virologically suppressed PWH switched non-nuclease reverse-transcriptase inhibitors (NNRTI; tenofovir-DF/emtricitabine with efavirenz to rilpivirine) and integrase-strand-transfer inhibitors (INSTI; tenofovir-DF/emtricitabine with raltegravir to dolutegravir). PWH were assessed by resting-state fMRI and stop-signal reaction time (SSRT) task fMRI as well as with a cognitive battery (CogState™) at baseline and follow-up. Switching from efavirenz to rilpivirine (n = 10) was associated with increased functional connectivity in the dorsal attention network (DAN) and a reduction in SSRTs (p = 0.025) that positively correlated with the time previously on efavirenz (mean = 4.8 years, p = 0.02). Switching from raltegravir to dolutegravir (n = 12) was associated with increased connectivity in the left DAN and bilateral sensory-motor and associative visual networks. In the NNRTI study, significant improvements in the cognitive domains of executive function, working memory and speed of visual processing were observed, whereas no significant changes in cognitive function were observed in the INSTI study. Changes in fMRI are evident in PWH without perceived neuropsychiatric complaints switching cART. fMRI may be a useful tool in assisting to elucidate the underlying pathogenic mechanisms of cART-related neuropsychiatric effects.

Journal article

El Bouzidi K, Jose S, Phillips AN, Pozniak A, Ustianowski A, Gompels M, Winston A, Schaap A, Dunn DT, Sabin CAet al., 2020, First-line HIV treatment outcomes following the introduction of integrase inhibitors in UK guidelines, AIDS, Vol: 34, Pages: 1823-1831, ISSN: 0269-9370

Journal article

Sabin CA, Kunisaki KM, Bagkeris E, Post FA, Sachikonye M, Boffito M, Anderson J, Mallon PWG, Williams I, Vera JH, Johnson M, Babalis D, Winston Aet al., 2020, Respiratory symptoms and chronic bronchitis in people with and without HIV infection, HIV MEDICINE, Vol: 22, Pages: 11-21, ISSN: 1464-2662

Journal article

Sabin CA, Harding R, Doyle N, Redline S, de Francesco D, Mallon PWG, Post FA, Boffito M, Sachikonye M, Geressu A, Winston A, Kunisaki KMet al., 2020, Associations between widespread pain and sleep quality in people with HIV, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 85, Pages: 106-112, ISSN: 1525-4135

Background: We investigate the association of widespread pain with sleep quality among people with HIV and HIV-negative controls.Setting: UK-based cohort.Methods: Pain information was collected through a pain mannikin identifying affected body sites; pain was classified as widespread if pain was reported in ≥4 of 5 body regions and in ≥7 of 15 body sites, and as regional otherwise. Sleep was assessed a median of 3.2 years later through 7-night actigraphy and through self-reported assessments of sleep quality. Chi-squared tests, Kruskal–Wallis tests, and linear/logistic regression considered associations between pain extent and sleep quality.Results: Of the 414 participants, 74 (17.9%) reported widespread and 189 (45.7%) regional pain. Although there were few clear associations between actigraphy outcomes and pain extent, those with widespread and regional pain consistently reported poorer sleep quality on all self-reported measures than those with no pain. Median (interquartile range) insomnia severity index and Patient-reported Outcomes Measurement Information System (PROMIS) for sleep disturbance and sleep-related impairment scores were 12 (7–16), 55.3 (48.0–58.9), and 57.2 (48.9–61.3), respectively, for those with widespread pain, 8 (4–13), 51.2 (45.5–58.3), and 50.3 (43.6–56.1) for those with regional pain, and 5 (2–9), 47.9 (42.9–54.3), and 45.5 (41.4–50.3) for those with no pain (all P values 0.0001). Associations remained strong after adjustment for HIV status and other confounders, and were reduced but remained significant, after adjustment for depressive symptoms.Conclusions: Widespread pain was not associated with objective measures of sleep but was strongly associated with self-reported assessments of sleep quality in people with HIV.

Journal article

Raffi F, Gaultier A, Pozniak A, Molina J-M, Jessen H, Antinori A, Soria A, Cavellec M, Le Thuaut A, Ningre M, de Wit Set al., 2020, Five-year follow-up of patients enrolled in the NEAT 001/ANRS 143 randomized clinical trial: NEAT 001/ANRS 143 LONG TERM study., J Antimicrob Chemother, Vol: 75, Pages: 1618-1622

BACKGROUND: Few long-term data are available in subjects having initiated ART with an NRTI-sparing regimen. OBJECTIVES: Outcomes of subjects enrolled in the NEAT 001/ANRS 143 randomized clinical trial (comparing ritonavir-boosted darunavir + raltegravir versus ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine) were retrospectively collected, through anonymized electronic case report forms, up to 6 years post-enrolment. METHODS: The last NEAT 001 visit (Week 96) was conducted in 745/805 randomized subjects (363/401 ritonavir-boosted darunavir + raltegravir and 382/404 ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine). Of these, 430 were enrolled in NEAT 001/ANRS 143 LONG TERM (NLT) study (201 raltegravir, 229 tenofovir disoproxil fumarate/emtricitabine), with a median follow-up of 44.4 months. RESULTS: During NLT follow-up, the proportion of AIDS, non-AIDS events, virological rebound and serious adverse events, discontinuation for virological failure and for adverse events did not differ between groups; discontinuations for virological failure since NEAT 001 inclusion were more frequent in subjects with baseline CD4 <200 cells/mm3 (11.9% versus 5.3%; P = 0.077). At last follow-up, a quarter of subjects (22.2% for ritonavir-boosted darunavir + raltegravir and 29.7% for ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine) were still receiving their initial regimen. Integrase inhibitor exposure was not associated with weight gain (P = 0.48), while tenofovir disoproxil fumarate exposure was associated with a trend to higher creatinine increase (P = 0.067). CONCLUSIONS: After a median of 5.6 years, subjects initiating ritonavir-boosted darunavir + raltegravir or ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine experienced few serious clinical adverse events. Most discontinuations were for reasons unrelated

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

Savinelli S, De Francesco D, Feeney ER, Babalis D, Bagkeris E, Post FA, Boffito M, Williams I, Vera J, Johnson M, Anderson J, Sachikonye M, Winston A, Sabin C, Mallon PWGet al., 2020, Factors associated with obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort: an observational cross-sectional analysis, HIV MEDICINE, Vol: 21, Pages: 441-452, ISSN: 1464-2662

Journal article

Wang X, Boffito M, Dickinson L, Bagkeris E, Khoo S, Post FA, Vera J, Williams I, Ndoutoumou A, Anderson J, Mallon P, McClure M, Winston A, Sabin Cet al., 2020, Plasma nucleotide reverse transcriptase inhibitor concentration and their associations with liver and renal parameters in people living with HIV, AIDS, Vol: 34, Pages: 790-793, ISSN: 0269-9370

Journal article

De Francesco D, Choi J-P, Choi JY, van Zoest RA, Underwood J, Schouten J, Ku NS, Kim WJ, Reiss P, Sabin CA, Winston A, Reiss P, Winston A, Wit FW, Prins M, van der Loeff MFS, Schouten J, Schmand B, Geurtsen GJ, Sharp DJ, Caan MWA, Majoie C, Villaudy J, Berkhout B, Kootstra NA, Gisslen M, Pasternak A, Sabin CA, Guaraldi G, Burkle A, Libert C, Franceschi C, Kalsbeek A, Fliers E, Hoeijmakers J, Pothof J, van der Valk M, Bisschop PH, Portegies P, Zaheri S, Burger D, Reiss P, Winston A, Wit FW, Cole JH, Caan MWA, Villaudy J, Kootstra NA, van der Loeff MFS, Gisslen M, Sabin CA, Burkle A, Zikkenheiner W, Reiss P, Zikkenheiner W, Wit FW, Janssen FR, Winston A, Wit FW, Underwood J, Schouten J, Kooij KW, van Zoest RA, Doyle N, Prins M, van der Loeff MS, Portegies P, Schmand BA, Geurtsen GJ, Verheij E, Verboeket SO, Elsenga BC, van der Valk M, Zaheri S, Hillebregt MMJ, Ruijs YMC, Benschop DP, Tembo L, McDonald L, Stott M, Legg K, Lovell A, Erlwein O, Kingsley C, Norsworthy P, Mullaney S, Kruijer T, del Grande L, Olthof V, Visser GR, May L, Verbraak F, Demirkaya N, Visser I, Guaraldi G, Sharp DJ, Caan MWA, Cole JH, Majoie CBLM, Su T, Leech R, Huguet J, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl A, Weijer K, Siteur-Van Rijnstra E, Kootstra NA, Gisslen M, Harskamp-Holwerda AM, Maurer I, Ruiz MMM, Girigorie AF, Boeser-Nunnink B, Kalsbeek A, Bisschop PHLT, Burger D, de Graaff-Teulen M, Hoeijmakers J, Pothof J, Libert C, Dewaele S, Franceschi C, Garagnani P, Pirazzini C, Capri M, Dall'Olio F, Chiricolo M, Salvioli S, Fuchs D, Zetterberg H, Weber D, Grune T, Jansen EHJM, Sabin CA, De Francesco D, Wit FW, Burkle A, Sindlinger T, Oehlke S, Zikkenheiner W, van Zoest RAet al., 2019, Cognitive function and drivers of cognitive impairment in a European and a Korean cohort of people living with HIV, INTERNATIONAL JOURNAL OF STD & AIDS, Vol: 31, Pages: 30-37, ISSN: 0956-4624

Journal article

Cole M, Saeed Z, Shaw A, Guo Y, Hoschler K, Winston A, Cooke G, Fidler S, Taylor G, Pollock Ket al., 2019, Responses to quadrivalent influenza vaccine reveal distinct circulating CD4+CXCR5+ T cell subsets in men living with HIV, Scientific Reports, Vol: 9, ISSN: 2045-2322

T cell help for B cells may be perturbed in people living with HIV (PLWH), even when HIV is suppressed, as evidenced by reports of suboptimal responses to influenza vaccination. We investigated cTFH responses to the 2017–18 inactivated quadrivalent influenza vaccine (QIV) in men living with antiretroviral therapy (ART)-suppressed HIV infection who were treated in the early or chronic phase of infection, and control subjects. Here we show that seroprotective antibody responses in serum and oral fluid correlated with cTFH activation and were equivalent in all three groups, irrespective of when ART was started. These responses were attenuated in those reporting immunisation with influenza vaccine in the preceding three years, independent of HIV infection. Measurement of influenza-specific IgG in oral fluid was closely correlated with haemagglutination inhibition titre. T-SNE and two-dimensional analysis revealed a subset of CD4+CXCR3+CXCR5+ cTFH activated at one week after vaccination. This was distinguishable from cTFH not activated by vaccination, and a rare, effector memory CD4+CXCR5hiCD32hi T cell subset. The data support the use of QIV for immunisation of PLWH, reveal distinct circulating CD4+CXCR5+ T cell subsets and demonstrate oral fluid sampling for influenza-specific IgG is an alternative to phlebotomy.

Journal article

De Francesco D, Underwood J, Bagkeris E, Anderson J, Williams I, Vera JH, Post FA, Boffito M, Johnson M, Mallon PWG, Winston A, Sabin CA, Mallon P, Post F, Sabin C, Sachikonye M, Ndoutoumou A, Babalis D, Asboe D, Garvey L, Pozniak A, Vera J, Campbell L, Yurdakul S, Okumu S, Pollard L, Suarez BS, Otiko D, Phillips L, Laverick R, Beynon M, Salz A-L, Severn A, Fisher M, Clarke A, Bexley A, Richardson C, Kirk S, Gleig R, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, McDermott A, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Ngwu N, Hemat N, Carroll A, Kinloch S, Youle M, Madge S, Tembo L, Stott M, McDonald L, Dransfield F, Bracchi M, Pagani N, Cerrone M, Bradshaw D, Ferretti F, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C, Fernando P, De Fran Det al., 2019, Risk factors and impact of patterns of co-occurring comorbidities in people living with HIV, AIDS, Vol: 33, Pages: 1871-1880, ISSN: 0269-9370

Journal article

Underwood J, de francesco D, Cole JH, Caan MWA, Van Zoest RA, Schmand BA, Sharp D, Sabin CA, Reiss P, Winston Aet al., 2019, Validation of a novel multivariate method of defining HIV-associated cognitive impairment, Open Forum Infectious Diseases, Vol: 6, ISSN: 2328-8957

BackgroundThe optimum method of defining cognitive impairment in virally suppressed people-living-with-HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient reported outcome measures (PROMs) and neuroimaging markers of brain structure across three cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs and neuroimaging data from the COBRA, CHARTER and POPPY cohorts (total n=908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS) and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (e.g. 48% for HAND vs. 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints were generally weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (p’s<0.05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (p’s<0.05), as well as smaller brain volumes (p<0.01). The associations with measures of white matter microstructure and brain-predicted age were generally weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.

Journal article

Alagaratnam J, Dilly-Penchala S, Challenger E, Else L, Legg K, Petersen C, Jones B, Kulasegaram R, Seyedkazemi S, Lefebvre E, Khoo S, Winston Aet al., 2019, Cerebrospinal fluid exposure of cenicriviroc in HIV-positive individuals with cognitive impairment, British Journal of Clinical Pharmacology, Vol: 85, Pages: 1039-1040, ISSN: 0306-5251

Journal article

Dhillon S, Sabin CA, Alagaratnam J, Bagkeris E, Post FA, Boffito M, Anderson J, Vera J, Williams I, Johnson M, Sachikonye M, Babalis D, Mallon PW, Winston A, Pharmacokinetic and Clinical Observations in People over Fifty POPPY studyet al., 2019, Level of agreement between frequently used cardiovascular risk calculators in people living with HIV, HIV Medicine, Vol: 20, Pages: 347-352, ISSN: 1464-2662

OBJECTIVES: The aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH). METHODS: PLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into 'low' (< 10%), 'intermediate' (10-20%) and 'high' (> 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland-Altman plots. RESULTS: The 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49-59] years. The median calculated 10-year CVD risk was 11.9% (IQR 6.8-18.4%), 8.9% (IQR 4.6-15.0%), 8.5% (IQR 4.8-14.6%) and 6.9% (IQR 4.1-11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50-0.60 range. CONCLUSIONS: Estimates of predicted 10-year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone.

Journal article

De Francesco D, Underwood J, Bagkeris E, Boffito M, Post FA, Mallon PWG, Vera JH, Williams I, Anderson J, Johnson M, Sabin CA, Winston A, Babalis D, Boffito M, Burgess L, Mallon P, Sabin C, Sachikonye M, Winston A, Asboe D, Garvey L, Pozniak A, Sabin C, Sachikonye M, Clarke A, Vera J, Bexley A, Richardson C, Kirk S, Gleig R, Asboe D, Pozniak A, Bracchi M, Pagani N, Cerrone M, Bradshaw D, Ferretti F, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C, Fernando P, Chiwome C, Hardwick S, Anderson J, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Post F, Campbell L, Yurdakul S, Okumu S, Pollard L, Santana-Suarez B, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, Babu S, Otiko D, Phillips L, Laverick R, Beynon M, Salz A-L, Severn A, Winston A, Garvey L, Tembo L, Stott M, McDonald L, Dransfield F, Whitehouse A, Burgess L, Babalis D, Ngwu N, Hemat N, Jones M, Carroll A, Kinloch S, Youle M, Madge S, Sabin Cet al., 2019, Depression, lifestyle factors and cognitive function in people living with HIV and comparable HIV-negative controls, HIV MEDICINE, Vol: 20, Pages: 274-285, ISSN: 1464-2662

Journal article

Alagaratnam J, Stohr W, Toombes J, Zetterberg H, Pett S, Nelson M, Kinloch S, Clarke A, Nwokolo N, Johnson M, Fox J, Hanke T, Babiker A, Frater J, Winston A, Fidler Set al., 2019, No evidence of neuroaxonal injury following latency reversal with vorinostat and HIV-1 specific vaccination in the RIVER trial, Publisher: WILEY, Pages: 25-25, ISSN: 1464-2662

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

Pool ERM, Winston A, Bagkeris E, Vera JH, Mallon PWG, Sachikonye M, Post FA, Pozniak A, Boffito M, Anderson J, Williams I, Johnson M, Burgess L, Sabin CAet al., 2019, High-risk behaviours, and their associations with mental health, adherence to antiretroviral therapy and HIV parameters, in HIV-positive men who have sex with men, HIV MEDICINE, Vol: 20, Pages: 131-136, ISSN: 1464-2662

Journal article

Tan DHS, Raboud JM, Szadkowski L, Grinsztejn B, Madruga JV, Figueroa MI, Cahn P, Barton SE, Clarke A, Fox J, Zubyk W, Walmsley SL, Brunetta J, Cameron W, Cohen J, Conway B, Fortin C, Fraser C, Kilby D, Klein M, Logue K, Pick N, Rachlis A, Romanowski B, Smaill F, Trottier S, Winston Aet al., 2019, Effect of valaciclovir on CD4 count decline in untreated HIV: an international randomized controlled trial, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 74, Pages: 480-488, ISSN: 0305-7453

Journal article

Keegan MR, Winston A, Higgs C, Fuchs D, Boasso A, Nelson Met al., 2019, Tryptophan metabolism and its relationship with central nervous system toxicity in people living with HIV switching from efavirenz to dolutegravir., J Neurovirol, Vol: 25, Pages: 85-90

The mechanisms underlying central nervous system (CNS) toxicities in antiretroviral-treated persons living with HIV (PLWH) remain elusive. We investigated the associations between markers of tryptophan metabolism and measurements of CNS toxicity in PLWH. In a prospective study, virologically suppressed PLWH receiving efavirenz-containing antiretroviral regimens with ongoing CNS toxicity were switched to dolutegravir-containing regimens and followed up for 12 weeks. Plasma tryptophan and kynurenine concentrations and the kynurenine/tryptophan ratio were calculated. Ten CNS toxicities were graded according to the ACTG adverse events scale. Scores ranged from 0 (none) to 3 (severe) and were summed, giving a total from 0 to 30. Paired-samples t tests and linear mixed model analyses were conducted to assess changes in, and relationships between, laboratory and clinical parameters. Mean kynurenine plasma concentration increased from baseline to week 12 (2.15 to 2.50 μmol/L, p = 0.041). No significant changes were observed for tryptophan (54.74 to 56.42 μmol/L, p = 1.000) or kynurenine/tryptophan ratio (40.37 to 41.08 μmol/L, p = 0.276). Mean CNS toxicity score decreased from 10.00 to 4.63 (p < 0.001). Plasma kynurenine concentration correlated with CNS toxicity score: for every 1 μmol/L increase in kynurenine concentration observed, a 1.7 point decrease was observed in CNS toxicity score (p < 0.038). A similar trend was observed for the kynurenine/tryptophan ratio: for every 1 μmol/mmol increase observed in kynurenine/tryptophan ratio, a 0.1 point decrease was observed in CNS toxicity score (p = 0.054). Switching from efavirenz to dolutegravir was associated with increases in plasma kynurenine concentration and improvements in CNS toxicity scores. Underlying mechanisms explaining the rise in kynurenine concentrations need to be established

Journal article

De Francesco D, Winston A, Underwood J, Cresswell FV, Anderson J, Post FA, Williams I, Mallon PWG, Sachikonye M, Babalis D, Vera JH, Bagkeris E, Milinkovic A, Sabin CAet al., 2019, Cognitive function, depressive symptoms and syphilis in HIV-positive and HIV-negative individuals, International Journal of STD and AIDS, ISSN: 0956-4624

© The Author(s) 2019. We evaluated associations between history of syphilis infection and both cognitive function and depressive symptoms in people living with HIV (PLHIV) and comparable HIV-negative controls. Syphilis serological tests, cognitive function and depression were assessed in PLHIV and controls participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study. Cognitive test scores were converted to demographically adjusted T-scores (mean = 50, SD = 10) and then averaged to obtain a global T-score. Severity of depressive symptoms was assessed via the Patient Health Questionnaire-9. Associations of syphilis with global T-scores and depression were assessed using median regression. The 623 PLHIV and 246 HIV-negative controls were predominantly male (89.3% and 66.5%) with median age (interquartile range [IQR]) of 57 (53–63) and 58 (53–63) years, respectively. PLHIV had lower global cognitive T-scores (median [IQR] 48.7 [45.1, 52.1] versus 50.5 [47.0, 53.9], p < 0.001), more severe depressive symptoms (median [IQR] 4 [1, 10] versus 1 [0, 3], p < 0.001) and were more likely to report history of syphilis infection (22.0% versus 8.1%) than controls. There was no significant association between history of syphilis and global cognitive function in either PLHIV (p = 0.69) or controls (p = 0.10). Participants with a history of syphilis had more severe depressive symptoms (median [IQR] 4 [1, 9] versus 2 [0, 8], p = 0.03); however, the association became non-significant (p = 0.62) after adjusting for HIV status and potential confounders. Despite the higher prevalence of syphilis infection in PLHIV, there was no evidence of an association between history of syphilis infection and impaired cognitive function nor depressive symptoms after accounting for potential confounders.

Journal article

Jose S, Hamzah L, Jones R, Williams D, Winston A, Burns F, Phillips AN, Sabin CA, Post FAet al., 2018, Chronic Kidney Disease Risk in African and Caribbean Populations With HIV, JOURNAL OF INFECTIOUS DISEASES, Vol: 218, Pages: 1767-1772, ISSN: 0022-1899

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00419464&limit=30&person=true