Imperial College London

ProfessorAlanWinston

Faculty of MedicineDepartment of Infectious Disease

Professor of Genito-Urinary Medicine
 
 
 
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Contact

 

+44 (0)20 3312 1603a.winston

 
 
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Location

 

Winston Churchill WingSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

377 results found

Nightingale S, Cinque P, Dravid A, Dreyer AJ, Gisslén M, Joska JA, Kwasa J, Meyer A-C, Mpongo N, Nakasujja N, Pebody R, Pozniak A, Price RW, Saylor D, Thomas KGF, Underwood J, Vera JH, Winston Aet al., 2024, Reply to 'Cognitive criteria in HIV: greater consensus is needed'., Nat Rev Neurol, Vol: 20, Pages: 129-130

Journal article

Ambrosioni J, Levi L, Alagaratnam J, Van Bremen K, Mastrangelo A, Waalewijn H, Molina J-M, Guaraldi G, Winston A, Boesecke C, Cinque P, Bamford A, Calmy A, Marzolini C, Martinez E, Oprea C, Welch S, Koval A, Mendao L, Rockstroh JK, EACS GBet al., 2023, Major revision version 12.0 of the European AIDS Clinical Society guidelines 2023, HIV MEDICINE, ISSN: 1464-2662

Journal article

Sukumaran L, Winston A, Sabin CA, 2023, Understanding the conditions included in data-driven patterns of multimorbidity: a scoping review, EUROPEAN JOURNAL OF PUBLIC HEALTH, ISSN: 1101-1262

Journal article

Arenas-Pinto A, Bakewell N, Milinkovic A, Williams I, Vera J, Post FA, Anderson J, Beynon M, O'Brien A, Doyle N, Gilson R, Pett SL, Winston A, Sabin CAet al., 2023, Hepatic steatosis in people older and younger than fifty who are living with HIV and HIV-negative controls: A cross-sectional study nested within the POPPY cohort, HIV MEDICINE, ISSN: 1464-2662

Journal article

Baker V, Nkhoma K, Trevelion R, Roach A, Winston A, Sabin C, Bristowe K, Harding Ret al., 2023, "I have failed to separate my HIV from this pain": the challenge of managing chronic pain among people with HIV, AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV, Vol: 35, Pages: 1164-1172, ISSN: 0954-0121

Journal article

Alagaratnam J, Sabin CA, Garvey LJ, Ramzan F, Winston A, Fidler S, Mackie NEet al., 2023, Evaluating virological outcomes in people with HIV on stable antiretroviral therapy with reduced frequency of HIV viral load monitoring during the COVID-19 pandemic, Publisher: WILEY, Pages: 845-850, ISSN: 1464-2662

Conference paper

Henderson M, Pepper N, Bawa M, Muir D, Everitt A, Mackie NE, Winston Aet al., 2023, Cerebrospinal fluid virology in people with HIV, HIV MEDICINE, Vol: 24, Pages: 838-844, ISSN: 1464-2662

Journal article

Rakshasa-Loots AM, Bakewell NJ, Sharp DJ, Gisslen M, Zetterberg H, Alagaratnam J, Wit FWNM, Kootstra NA, Winston A, Reiss PA, Sabin CAH, Vera JHet al., 2023, Biomarkers of central and peripheral inflammation mediate the association between HIV and depressive symptoms, TRANSLATIONAL PSYCHIATRY, Vol: 13, ISSN: 2158-3188

Journal article

Bawa M, Henderson M, Pepper N, Muir D, Everitt A, Mackie N, Winston Aet al., 2023, Cerebrospinal fluid HIV RNA and viral nucleic acid detection in persons with HIV, Publisher: WILEY, Pages: 52-52, ISSN: 1464-2662

Conference paper

Okhai H, Winston A, Post F, Boffito M, Mallon P, Vera J, Williams I, Sachikonye M, Johnson M, Anderson J, Prechtl C, Sabin Cet al., 2023, Rate of persistent depressive symptoms among participants in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study, Publisher: WILEY, Pages: 13-14, ISSN: 1464-2662

Conference paper

Sukumaran L, Kunisaki KM, Bakewell N, Winston A, Mallon PWG, Doyle N, Anderson J, Boffito M, Williams I, Post FA, Vera J, Sachikonye M, Sabin CAet al., 2023, Associations between inflammatory profiles and multimorbidity burden among people living with HIV, Publisher: WILEY, Pages: 54-55, ISSN: 1464-2662

Conference paper

MacDonald DM, Samorodnitsky S, Wendt CH, Baker JV, Collins G, Kruk M, Lock EF, Paredes R, Poongulali S, Weise DO, Winston A, Wood R, Kunisaki KM, INSIGHT START Pulmonary Substudy Groupet al., 2023, Pneumoproteins and biomarkers of inflammation and coagulation do not predict rapid lung function decline in people living with HIV., Sci Rep, Vol: 13

Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide and HIV is an independent risk factor for the development of COPD. However, the etiology of this increased risk and means to identify persons with HIV (PWH) at highest risk for COPD have remained elusive. Biomarkers may reveal etiologic pathways and allow better COPD risk stratification. We performed a matched case:control study of PWH in the Strategic Timing of Antiretoviral Treatment (START) pulmonary substudy. Cases had rapid lung function decline (> 40 mL/year FEV1 decline) and controls had stable lung function (+ 20 to - 20 mL/year). The analysis was performed in two distinct groups: (1) those who were virally suppressed for at least 6 months and (2) those with untreated HIV (from the START deferred treatment arm). We used linear mixed effects models to test the relationship between case:control status and blood concentrations of pneumoproteins (surfactant protein-D and club cell secretory protein), and biomarkers of inflammation (IL-6 and hsCRP) and coagulation (d-dimer and fibrinogen); concentrations were measured within ± 6 months of first included spirometry. We included an interaction with treatment group (untreated HIV vs viral suppression) to test if associations varied by treatment group. This analysis included 77 matched case:control pairs in the virally suppressed batch, and 42 matched case:control pairs in the untreated HIV batch (n = 238 total) who were followed for a median of 3 years. Median (IQR) CD4 + count was lowest in the controls with untreated HIV at 674 (580, 838). We found no significant associations between case:control status and pneumoprotein or biomarker concentrations in either virally suppressed or untreated PWH. In this cohort of relatively young, recently diagnosed PWH, concentrations of pneumoproteins and biomarkers of inflammation and coagulation were

Journal article

Aung HL, Alagaratnam J, Chan P, Chow FC, Joska J, Falutz J, Letendre SL, Lin W, Muñoz-Moreno JA, Cinque P, Taylor J, Brew B, Winston Aet al., 2023, Cognitive health in persons with human immunodeficiency virus: the impact of early treatment, comorbidities, and aging, Journal of Infectious Diseases, Vol: 227, Pages: S38-S47, ISSN: 0022-1899

With the advent of virally suppressive antiretroviral therapy (ART), life expectancy for persons with human immunodeficiency virus (HIV) with access to ART now approaches that of the general population. As persons with HIV age, noninfectious comorbidities occur more frequently compared with persons without HIV. Such comorbidities are likely to affect cognitive health, which may also be affected by lifestyle factors that may differ in persons with HIV.At the National Institutes of Health–supported meeting on Biotypes of Central Nervous System (CNS) Complications in persons with HIV, a session was devoted to early HIV treatment, noninfectious comorbidities, and aging as each pertains to cognitive health. Areas of consideration included acute and early HIV infection (presentation by Phillip Chan), drugs of abuse (Scott Letendre), stroke and cerebrovascular disease (Felicia Chow), mental health (John Joska), and aging (Julian Falutz).These presentations were followed by a discussion session led by Woody Lin, Jose A. Muñoz-Moreno, Paola Cinque, and Jeff Taylor. Alan Winston and Bruce Brew chaired the meeting with Jasmini Alagaratnam and Htein Linn Aung acting as rapporteurs.Here we present the main topics covered in the presentations, and the associated discussions highlighting knowledge gaps and future directions.

Journal article

Sukumaran L, Kunisaki KM, Bakewell N, Winston A, Mallon PWG, Doyle N, Anderson J, Boffito M, Haddow L, Post FA, Vera JH, Sachikonye M, Sabin CAet al., 2023, Association between inflammatory biomarker profiles and cardiovascular risk in individuals with and without HIV, AIDS, Vol: 37, Pages: 595-603, ISSN: 0269-9370

Journal article

Nikolaichuk M, Mocroft A, Wandeler G, Szlavik J, Gottfredsson M, Reikvam DH, Svedhem V, Elinav H, Laguno M, Mansinho K, Devitt E, Chkhartishvili N, Behrens G, Bogner J, Viard J-P, Winston A, Benfield T, Leen C, Fursa O, Rockstroh J, Peters L, EuroSIDA study groupet al., 2023, Use of contraindicated antiretroviral drugs in people with HIV/HCV coinfections receiving HCV treatment with direct-acting antivirals-Results from the EuroSIDA study., HIV Med, Vol: 24, Pages: 224-230

OBJECTIVES: Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. METHODS: At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications ('red shading' in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. RESULTS: Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3-8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40-7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08-0.65) for 2015-2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). CONCLUSION: In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interact

Journal article

Szubert AJ, Pollock KM, Cheeseman HM, Alagaratnam J, Bern H, Bird O, Boffito M, Byrne R, Cole T, Cosgrove CA, Faust SN, Fidler S, Galiza E, Hassanin H, Kalyan M, Libri V, McFarlane LR, Milinkovic A, O'Hara J, Owen DR, Owens D, Pacurar M, Rampling T, Skene S, Winston A, Woolley J, Yim YTN, Dunn DT, McCormack S, Shattock RJ, COVAC 1 Study Teamet al., 2023, COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2., EClinicalMedicine, Vol: 56, Pages: 1-13, ISSN: 2589-5370

BACKGROUND: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is well tolerated and immunogenic in SARS-CoV-2 seronegative and seropositive individuals aged 18-75. METHODS: A phase 2a expanded safety and immunogenicity study of a saRNA SARS-CoV-2 vaccine candidate LNP-nCoVsaRNA, was conducted at participating centres in the UK between 10th August 2020 and 30th July 2021. Participants received 1 μg then 10 μg of LNP-nCoVsaRNA, ∼14 weeks apart. Solicited adverse events (AEs) were collected for one week post-each vaccine, and unsolicited AEs throughout. Binding and neutralisating anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, and SARS-CoV-2 pseudoneutralisation assay. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). FINDINGS: 216 healthy individuals (median age 51 years) received 1.0 μg followed by 10.0 μg of the vaccine. 28/216 participants were either known to have previous SARS-CoV2 infection and/or were positive for anti-Spike (S) IgG at baseline. Reactogenicity was as expected based on the reactions following licensed COVID-19 vaccines, and there were no serious AEs related to vaccination. 80% of baseline SARS-CoV-2 naïve individuals (147/183) seroconverted two weeks post second immunization, irrespective of age (18-75); 56% (102/183) had detectable neutralising antibodies. Almost all (28/31) SARS-CoV-2 positive individuals had increased S IgG binding antibodies following their first 1.0 μg dose with a ≥0.5log10 increase in 71% (22/31). INTERPRETATION: Encapsulated saRNA was well tolerated and immunogenic in adults aged 18-75 years. Seroconversion rates in antigen naïve were higher than those reported in our dose-ranging study. Further work is required to determine if this difference is related to a longer dosing interval (14 vs. 4 weeks) or dosing with 1.0 μg followed by 10.0 μg. Boosting of S IgG an

Journal article

Fidler S, Fox J, Tipoe T, Longet S, Tipton T, Abeywickrema M, Adele S, Alagaratnam J, Ali M, Aley PK, Aslam S, Balasubramanian A, Bara A, Bawa T, Brown A, Brown H, Cappuccini F, Davies S, Fowler J, Godfrey L, Goodman AL, Hilario K, Hackstein CP, Mathew M, Mujadidi YF, Packham A, Petersen C, Plested E, Pollock KM, Ramasamy MN, Robinson H, Robinson N, Rongkard P, Sanders H, Serafimova T, Spence N, Waters A, Woods D, Zacharopoulou P, Barnes E, Dunachie S, Goulder P, Klenerman P, Winston A, Hill AVS, Gilbert SC, Carroll M, Pollard AJ, Lambe T, Ogbe A, Frater Jet al., 2023, Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV, Clinical Infectious Diseases, Vol: 76, Pages: 201-209, ISSN: 1058-4838

BACKGROUND: People with HIV on antiretroviral therapy with good CD4 T cell counts make effective immune responses following vaccination against SARS-CoV-2. There are few data on longer term responses and the impact of a booster dose. METHODS: Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed twelve months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µl. Immune responses to the ancestral strain and variants of concern were measured by anti-spike IgG ELISA, MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, Activation Induced Marker (AIM) assay and T cell proliferation. FINDINGS: 54 participants received two doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) one year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titres (MSD), ACE-2 inhibition and IgG ELISA results were significantly higher compared to Day 182 titres (P < 0.0001 for all three). SARS-CoV-2 specific CD4+ T cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4 + and CD8+ T cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B and T cell immunity, including to known VOCs.

Journal article

Yu X, Lobo JDD, Sundermann E, Baker DJJ, Tracy RPP, Kuchel GAA, Stephenson KEE, Letendre SLL, Brew B, Cysique LAA, Dale SKK, Wallen C, Kunisaki KMM, Guaraldi G, Milic J, Winston A, Moore DJJ, Margolick JBB, Erlandson KMMet al., 2023, Current Challenges and Solutions for Clinical Management and Care of People with HIV: Findings from the 12th Annual International HIV and Aging Workshop, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 39, Pages: 1-12, ISSN: 0889-2229

Journal article

Waters L, Winston A, Reeves I, Boffito M, Churchill D, Cromarty B, Dunn D, Fink D, Fidler S, Foster C, Fox J, Gupta R, Hilton A, Khoo S, Leen C, Mackie N, Naous N, Ogbonmwan D, Orkin C, Panton L, Post F, Pozniak A, Sabin C, Walsh Jet al., 2022, BHIVA guidelines on antiretroviral treatment for adults living with HIV-1 2022, HIV MEDICINE, Vol: 23, Pages: 3-115, ISSN: 1464-2662

Journal article

Elliott T, Cheeseman HM, Evans AB, Day S, McFarlane LR, O'Hara J, Kalyan M, Amini F, Cole T, Winston A, Fidler S, Pollock KM, Harker JA, Shattock RJet al., 2022, Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines, PLoS Pathogens, Vol: 18, Pages: 1-20, ISSN: 1553-7366

The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-ƴ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2nd authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly e

Journal article

Alagaratnam J, Winston A, 2022, Molecular neuroimaging of inflammation in HIV, Clinical and Experimental Immunology, Vol: 210, Pages: 14-23, ISSN: 0009-9104

People-with-HIV now have near-normal life expectancies due to the success of effective combination antiretroviral therapy (cART). Following cART initiation, immune recovery occurs, and opportunistic diseases become rare. Despite this, high rates of non-infectious comorbidities persist in treated people-with-HIV, hypothesised to be related to persistent immuno-activation. One such comorbidity is cognitive impairment, which may partly be driven by ongoing neuro-inflammation in otherwise effectively-treated people-with-HIV. In order to develop therapeutic interventions to address neuro-inflammation in effectively-treated people-with-HIV, a deeper understanding of the pathogenic mechanisms driving persistent neuro-inflammatory responses and the ability to better characterise and measure neuro-inflammation in the central nervous system is required. This review highlights recent advances in molecular neuroimaging techniques which have the potential to assess neuro-inflammatory responses within the central nervous system in HIV-disease. Proton magnetic resonance spectroscopy ( 1H-MRS) has been utilised to assess neuro-inflammatory responses since early in the HIV pandemic and shows promise in recent studies assessing different antiretroviral regimens. 1H-MRS is widely available in both resource-rich and some resource-constrained settings and is relatively inexpensive. Brain positron emission tomography (PET) imaging using Translocator Protein (TSPO) radioligands is a rapidly evolving field; newer TSPO-radioligands have lower signal-to-noise ratio and have the potential to localise neuro-inflammation within the brain in people-with-HIV. As HIV therapeutics evolve, people-with-HIV continue to age and develop age-related comorbidities including cognitive disorders. The use of novel neuroimaging modalities in the field is likely to advance in order to rapidly assess novel therapeutic interventions and may play a role in future clinical assessments.

Journal article

Waters L, Winston A, Reeves I, Boffito M, Churchill D, Cromarty Bet al., 2022, IN BRIEF: BHIVA guidelines on antiretroviral treatment for adults living with HIV-1 2022 (vol 23, pg 3, 2022), HIV MEDICINE, Vol: 23, ISSN: 1464-2662

Journal article

Ryom L, De Miguel R, Cotter AG, Podlekareva D, Beguelin C, Waalewijn H, Arribas JR, Mallon PWG, Marzolini C, Kirk O, Bamford A, Rauch A, Molina JM, Kowalska JD, Guaraldi G, Winston A, Boesecke C, Cinque P, Welch S, Collins S, Behrens GMNet al., 2022, Major revision version 11.0 of the European AIDS Clinical Society Guidelines 2021, HIV MEDICINE, Vol: 23, Pages: 849-858, ISSN: 1464-2662

Journal article

Heskin J, Belfield A, Milne C, Brown N, Walters Y, Scott C, Bracchi M, Moore LS, Mughal N, Rampling T, Winston A, Nelson M, Duncan S, Jones R, Price DA, Mora-Peris Bet al., 2022, Transmission of monkeypox virus through sexual contact - A novel route of infection., Journal of Infection, Vol: 85, Pages: 334-363, ISSN: 0163-4453

Journal article

Ulfhammer G, Eden A, Antinori A, Brew BJ, Calcagno A, Cinque P, De Zan V, Hagberg L, Lin A, Nilsson S, Oprea C, Pinnetti C, Spudich S, Trunfio M, Winston A, Price RW, Gisslen Met al., 2022, Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study, CLINICAL INFECTIOUS DISEASES, Vol: 75, Pages: 493-502, ISSN: 1058-4838

Journal article

Shiva F, Short C-E, Goldmeier D, Winston Aet al., 2022, Predictive value of neurological symptoms in persons with suspected neurosyphilis, SEXUALLY TRANSMITTED INFECTIONS, Vol: 98, Pages: 228-229, ISSN: 1368-4973

Journal article

Ogbe A, Pace M, Bittaye M, Tipoe T, Adele S, Alagaratnam J, Aley PK, Ansari MA, Bara A, Broadhead S, Brown A, Brown H, Cappuccini F, Cinardo P, Dejnirattisai W, Ewer KJ, Fok H, Folegatti PM, Fowler J, Godfrey L, Goodman AL, Jackson B, Jenkin D, Jones M, Longet S, Makinson RA, Marchevsky NG, Mathew M, Mazzella A, Mujadidi YF, Parolini L, Petersen C, Plested E, Pollock KM, Rajeswaran T, Ramasamy MN, Rhead S, Robinson H, Robinson N, Sanders H, Serrano S, Tipton T, Waters A, Zacharopoulou P, Barnes E, Dunachie S, Goulder P, Klenerman P, Screaton GR, Winston A, Hill AVS, Gilbert SC, Carroll M, Pollard AJ, Fidler S, Fox J, Lambe T, Frater Jet al., 2022, Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV, JCI Insight, Vol: 7, Pages: 1-18, ISSN: 2379-3708

Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells > 350 cells/μL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4–6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that, 6 months after vaccination, the majority of measurable immune responses were greater than prevaccination baseline but with evidence of a decline in both humoral and cell-mediated immunity. There was, however, no significant difference compared with a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although they were lower than WT. Preexisting cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater postvaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the ongoing policy to vaccinate PWH against SARS-CoV-2, and they underpin the need for long-term monitoring of responses after vaccination.

Journal article

Doctor J, Winston A, Vera JH, Post FA, Boffito M, Mallon PWG, Anderson J, Prechtl C, Williams I, Johnson M, Bagkeris E, Sachikonye M, Sabin CA, POPPY Set al., 2022, Anticholinergic medications associated with falls and frailty in people with HIV, Publisher: WILEY, Pages: 10-11, ISSN: 1464-2662

Conference paper

Pollock KM, Cheeseman HM, Szubert AJ, Libri V, Boffito M, Owen D, Bern H, O'Hara J, McFarlane LR, Lemm N-M, McKay PF, Rampling T, Yim YTN, Milinkovic A, Kingsley C, Cole T, Fagerbrink S, Aban M, Tanaka M, Mehdipour S, Robbins A, Budd W, Faust SN, Hassanin H, Cosgrove CA, Winston A, Fidler S, Dunn DT, McCormack S, Shattock RJ, COVAC1 study Groupet al., 2022, Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial, EClinicalMedicine, Vol: 44, ISSN: 2589-5370

Background: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19. Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19th June to 28th October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0.1-10.0μg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). Findings: 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p<0.001), ranging from 8% (3/39; 0.1μg) to 61% (14/23; 10.0μg) in ELISA and 46% (18/39; 0.3μg) to 87% (20/23; 5.0μg and 10.0μg) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG concentrations ranged from 74 (95% CI, 45-119) at 0.1μg to 1023 (468-2236) ng/mL at 5.0μg (p<0.001) and was not higher at 10.0μg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15% (6/39; 0.1μg) to 48% (11/23; 5.0μg) depending on dose level received. Interpretation: Encapsulated saRNA is safe for clinical development, is immunogenic at low dose levels but failed to induce 100% seroconversion. Modifications to optimis

Journal article

Alagaratnam J, De Francesco D, Zetterberg H, Heslegrave A, Toombs J, Kootstra NA, Underwood J, Gisslen M, Reiss P, Fidler S, Sabin CA, Winston Aet al., 2022, Correlation between cerebrospinal fluid and plasma neurofilament light protein in treated HIV infection: results from the COBRA study, JOURNAL OF NEUROVIROLOGY, Vol: 28, Pages: 54-63, ISSN: 1355-0284

Journal article

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