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
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379 results found

Mora-Peris B, Bouliotis G, Kulasegaram R, Clarke A, Post FA, Nelson M, Burgess L, Tiraboschi J, Khoo S, Taylor S, Ashby D, Winston Aet al., 2018, Changes in cerebral function parameters with maraviroc intensified antiretroviral therapy in treatment naïve HIV-Positive individuals; A randomised controlled study, AIDS, Vol: 32, Pages: 1007-1015, ISSN: 0269-9370

Background: Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits.Methods: Therapy-naive, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1 : 1 basis to standard ART (Arm1: tenofovir-emtricitabine and atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine and darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy. Our primary endpoint was mean change in cognitive function across treatment arms with factors associated with cognitive function changes also assessed.Results: Of 60 individuals randomized (30 Arm1 and 30 Arm2), 58 were men and 44 of white ethnicity. Treatment groups had similar disease characteristics including overall mean (SD) baseline CD4+ cell count 428 (209) and 414 (229) cells/μl, Arms1 and 2, respectively. At week 48, plasma HIV RNA was less than 50 copies/ml in 55 of 56 of those completing study procedures. Cognitive function improved over 48 weeks [mean change z-score (SD) 0.16 (0.09) Arm1 and 0.25 (0.08) Arm2, P = 0.96 for differences between study arms]. A greater increase in frontal grey matter N-acetyl aspartate/creatine ratio was observed in Arm1 [ratio change of 0.071 (SD 0.16)] versus Arm2 [change −0.097 (SD 0.18), P = 0.009], although this was not associated with changes in cognitive function (P = 0.17).Conclusion: Maraviroc-intensified ART had no demonstrable benefit on cognitive function in individuals initiating ART. Greater improvement in neuronal metabolites (N-acetyl aspartate/creatine) was observed with standard ART. Future work should focus on maraviroc-intensified ART in individuals with cognitive impairment.

Journal article

Wright EJ, Grund B, Robertson KR, Cysique L, Brew BJ, Collins GL, Poehlman-Roediger M, Vjecha MJ, Penalva de Oliveira AC, Standridge B, Carey C, Avihingsanon A, Florence E, Lundgren JD, Arenas-Pinto A, Mueller NJ, Winston A, Nsubuga MS, Lal L, Price RWet al., 2018, No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4<SUP>+</SUP> T-cell counts, AIDS, Vol: 32, Pages: 985-997, ISSN: 0269-9370

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

Underwood J, De Francesco D, Leech R, Sabin CA, Winston Aet al., 2018, Medicalising normality? Using a simulated dataset to assess the performance of different diagnostic criteria of HIV-associated cognitive impairment, PLoS ONE, Vol: 13, ISSN: 1932-6203

ObjectiveThe reported prevalence of cognitive impairment remains similar to that reported in the pre-antiretroviral therapy era. This may be partially artefactual due to the methods used to diagnose impairment. In this study, we evaluated the diagnostic performance of the HIV-associated neurocognitive disorder (Frascati criteria) and global deficit score (GDS) methods in comparison to a new, multivariate method of diagnosis.MethodsUsing a simulated ‘normative’ dataset informed by real-world cognitive data from the observational Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) cohort study, we evaluated the apparent prevalence of cognitive impairment using the Frascati and GDS definitions, as well as a novel multivariate method based on the Mahalanobis distance. We then quantified the diagnostic properties (including positive and negative predictive values and accuracy) of each method, using bootstrapping with 10,000 replicates, with a separate ‘test’ dataset to which a pre-defined proportion of ‘impaired’ individuals had been added.ResultsThe simulated normative dataset demonstrated that up to ~26% of a normative control population would be diagnosed with cognitive impairment with the Frascati criteria and ~20% with the GDS. In contrast, the multivariate Mahalanobis distance method identified impairment in ~5%. Using the test dataset, diagnostic accuracy [95% confidence intervals] and positive predictive value (PPV) was best for the multivariate method vs. Frascati and GDS (accuracy: 92.8% [90.3–95.2%] vs. 76.1% [72.1–80.0%] and 80.6% [76.6–84.5%] respectively; PPV: 61.2% [48.3–72.2%] vs. 29.4% [22.2–36.8%] and 33.9% [25.6–42.3%] respectively). Increasing the a priori false positive rate for the multivariate Mahalanobis distance method from 5% to 15% resulted in an increase in sensitivity from 77.4% (64.5–89.4%) to 92.2% (83.3–100%) at a cost of specificity from

Journal article

Mallon P, Winston A, Post F, Bergin C, Yan M, Das M, Rhee Met al., 2018, Platelet function upon switching to tenofovir alafenamide (TAF) verses continuing abacavir (ABC): a randomised substudy OVERRIDE, Publisher: WILEY, Pages: S17-S18, ISSN: 1464-2662

Conference paper

Shiva F, Goldmeier D, Winston A, 2018, Neurosyphilis diagnosis; is cerebrospinal fluid examination helpful?, Publisher: WILEY, Pages: S138-S138, ISSN: 1464-2662

Conference paper

De Francesco D, Winston A, Choi JY, van Zoest RA, Underwood J, Schouten J, Ku NS, Kim WJ, Reiss P, Sabin CAet al., 2018, Determinants of cognitive function differ in a European and a Korean cohort, Publisher: WILEY, Pages: S75-S75, ISSN: 1464-2662

Conference paper

Wang X, Boffito M, Dickinson L, Bagkeris E, Khoo S, Post F, Mallon P, Vera J, Williams I, Babalis D, Anderson J, McClure M, Winston A, Sabin Cet al., 2018, Plasma NRTI concentrations and renal function in people with HIV, Publisher: WILEY, Pages: S16-S17, ISSN: 1464-2662

Conference paper

Petersen C, Alagaratnam J, Wood M, Ramzan F, Foster C, Fidler S, Winston Aet al., 2018, Frequency and reasons for switching integrase inhibitor-based ART, Publisher: WILEY, Pages: S11-S11, ISSN: 1464-2662

Conference paper

Francesco DD, Underwood J, Vera JH, Bagkeris E, Asboe D, Mallon PWG, Post FA, Johnson M, Williams I, Boffito M, Greliak P, Anderson J, Sabin CA, Winston Aet al., 2018, Associations between cognitive function and cardiovascular risk factors: differences between people with HIV and HIV-negative controls, Publisher: WILEY, Pages: S10-S11, ISSN: 1464-2662

Conference paper

De Francesco D, Wit FW, Cole JH, Kootstra NA, Winston A, Sabin CA, Underwood J, van Zoest RA, Schouten J, Kooij KW, Prins M, Guaraldi G, Caan MWA, Burger D, Franceschi C, Libert C, Bürkle A, Reiss P, COmorBidity in Relation to AIDS COBRA collaborationet al., 2018, The 'COmorBidity in Relation to AIDS' (COBRA) cohort: Design, methods and participant characteristics, PLoS ONE, Vol: 13, ISSN: 1932-6203

BACKGROUND: Persons living with HIV on combination antiretroviral therapy (cART) may be at increased risk of the development of age-associated non-communicable comorbidities (AANCC) at relatively young age. It has therefore been hypothesised that such individuals, despite effective cART, may be prone to accelerated aging. OBJECTIVE: The COmorBidity in Relation to AIDS (COBRA) cohort study was designed to investigate the potential causal link between HIV and AANCC, amongst others, in a cohort of middle-aged individuals with HIV with sustained viral suppression on cART and otherwise comparable HIV-negative controls. METHODS: Longitudinal cohort study of HIV-positive subjects ≥45 years of age, with sustained HIV suppression on cART recruited from two large European HIV treatment centres and similarly-aged HIV-negative controls recruited from sexual health centres and targeted community groups. Both HIV-positive and HIV-negative subjects were assessed at study entry and again at follow-up after 2 years. RESULTS: Of the 134 HIV-positive individuals with a median (IQR) age of 56 (51, 62) years recruited, 93% were male, 88% of white ethnicity and 86% were men who have sex with men (MSM). Similarly, the 79 HIV-negative subjects had a median (IQR) age of 57 (52, 64) and 92% were male, 97% of white ethnicity and 80% were MSM. CONCLUSIONS: The results from the COBRA study will be a significant resource to understand the link between HIV and AANCC and the pathogenic mechanisms underlying this link. COBRA will inform future development of novel prognostic tools for earlier diagnosis of AANCC and of novel interventions which, as an adjunct to cART, may prevent AANCC.

Journal article

Winston A, Post FA, DeJesus E, Podzamczer D, Di Perri G, Estrada V, Raffi F, Ruane P, Peyrani P, Crofoot G, Mallon PWG, Castelli F, Yan M, Cox S, Das M, Cheng A, Rhee MSet al., 2018, Tenofovir alafenamide plus emtricitabine versus abacavir plus lamivudine for treatment of virologically suppressed HIV-1-infected adults: a randomised, double-blind, active-controlled, non-inferiority phase 3 trial, Lancet HIV, Vol: 5, Pages: e162-e171, ISSN: 2405-4704

BACKGROUND: Abacavir and tenofovir alafenamide offer reduced bone toxicity compared with tenofovir disoproxil fumarate. We aimed to compare safety and efficacy of tenofovir alafenamide plus emtricitabine with that of abacavir plus lamivudine. METHODS: In this randomised, double-blind, active-controlled, non-inferiority phase 3 trial, HIV-1-positive adults (≥18 years) were screened at 79 sites in 11 countries in North America and Europe. Eligible participants were virologically suppressed (HIV-1 RNA <50 copies per mL) and on a stable three-drug regimen containing abacavir plus lamivudine. Participants were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to switch to fixed-dose tablets of tenofovir alafenamide (10 mg or 25 mg) plus emtricitabine (200 mg) or remain on abacavir (600 mg) plus lamivudine (300 mg), with matching placebo, while continuing to take the third drug. Randomisation was stratified by the third drug (boosted protease inhibitor vs other drug) at screening. Investigators, participants, and study staff giving treatment, assessing outcomes, and collecting data were masked to treatment group. The primary endpoint was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 48 (assessed by snapshot algorithm), with a 10% non-inferiority margin. We analysed the primary endpoint in participants enrolled before May 23, 2016 (when target sample size was reached), and we analysed safety in all enrolled participants who received at least one dose of study drug (including patients enrolled after these dates). This study was registered with ClinicalTrials.gov, number NCT02469246. FINDINGS: Study enrolment began on June 29, 2015, and the cutoff enrolment date for the week 48 primary endpoint analysis was May 23, 2016. 501 participants were randomly assigned and treated. At week 48, virological suppression was maintained in 227 (90%) of 253 participants receiving tenofovir alafena

Journal article

Haddow L, Laverick R, Leung I, Post F, Vera J, Gilson R, Williams I, Boffito M, Sabin C, Winston A, Peto Tet al., 2018, Measurement of Retinal Vessels as a Biomarker of Cerebrovascular Aging in Older HIV-Positive Men Compared With Controls, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 77, Pages: 199-205, ISSN: 1525-4135

Journal article

Haddow L, Laverick R, Leung I, Post F, Vera J, Gilson R, Williams I, Boffito M, Sabin C, Winston A, Peto Tet al., 2018, Measurement of Retinal Vessels as a Biomarker of Cerebrovascular Aging in Older HIV-Positive Men Compared With Controls., J Acquir Immune Defic Syndr, Vol: 77, Pages: 199-205

BACKGROUND: To compare retinal vascular measurements, biomarkers of cerebral small vessel disease, in HIV-positive men aged 50 years and older with similarly aged HIV-negative men and younger HIV-positive men. METHODS: We recruited white, nondiabetic men into a cross-sectional substudy of a larger cohort including 3 demographically matched groups. Optic disc-centered 45-degree color fundus photographs were used to calculate central retinal arterial and venous caliber and the arterial-venous ratio (AVR). We used univariate and multivariable linear regression to compare retinal vessel measurements in the 3 groups and to identify factors associated with AVR. RESULTS: All HIV-positive men were virologically suppressed. In a multivariable model, study group was not associated with AVR [adjusted β 0.010 for HIV-positive men <50 (n = 39) compared with HIV-positive men aged ≥50 years (n = 120), 95% confidence interval [CI] -0.018 to 0.038, P = 0.47; adjusted β 0.00002 for HIV-negative men ≥50 years (n = 52), 95% CI -0.022 to 0.022, P = 0.99]. Factors associated with lower AVR were systolic blood pressure (adjusted β -0.009 per +10 mm Hg, 95% CI -0.015 to -0.003, P = 0.002), history of stroke or transient ischemic attack (adjusted β -0.070, 95% CI -0.12 to -0.015, P = 0.01), and recent recreational drug use (adjusted β -0.037, 95% CI -0.057 to -0.018, P = 0.0002). CONCLUSIONS: There were no differences in retinal vascular indices between HIV-positive men aged ≥50 years and HIV-negative men aged ≥50 years or HIV-positive men aged <50 years, suggesting that HIV is not associated with an increased burden of cerebral small vessel disease.

Journal article

Solomon D, Sabin CA, Mallon PWG, Winston A, Tariq Set al., 2018, Cardiovascular disease in women living with HIV: A narrative review, MATURITAS, Vol: 108, Pages: 58-70, ISSN: 0378-5122

Journal article

Di Carlofelice M, Everitt A, Muir D, Winston Aet al., 2018, Cerebrospinal fluid HIV RNA in persons living with HIV, HIV Medicine, Vol: 19, Pages: 365-368, ISSN: 1464-2662

OBJECTIVES: Despite adequate suppression of plasma HIV RNA, viral escape in cerebrospinal fluid (CSF) is widely reported. Rates of CSF HIV RNA escape vary in the literature. In persons living with HIV (PLWH) undergoing lumbar puncture examination for clinical reasons, we assessed rates of CSF HIV RNA escape. METHODS: Persons living with HIV attending a designated HIV neurology service undergoing CSF assessment for clinical reasons between January 2015 and April 2017 were included in the study. CSF HIV RNA escape was defined as HIV RNA ≥ 0.5 log10 HIV-1 RNA copies/mL higher than plasma HIV RNA or detectable CSF HIV RNA when plasma HIV RNA was < 20 copies/mL. Clinical factors associated with CSF HIV RNA were assessed using logistic regression modelling. RESULTS: Of 38 individuals, 35 were receiving antiretroviral therapy, 30 were male and their mean age was 51 years. Clinical reasons for CSF assessment included investigation for cognitive decline (n = 25), early syphilis (n = 4) and other central nervous system (CNS) conditions (n = 9). HIV RNA was detectable in plasma and CSF in seven and six individuals, respectively, with two individuals (5.3%) meeting the definition of CSF escape. Detectable CSF HIV RNA was associated with a detectable plasma HIV RNA (P < 0.001) and a history of known antiretroviral drug resistance mutations (P = 0.021). CONCLUSIONS: The prevalence of CSF viral escape in PLWH undergoing lumbar puncture examination for clinical reasons is lower than previously reported.

Journal article

Caniglia EC, Phillips A, Porter K, Sabin CA, Winston A, Logan R, Gill J, Vandenhende M-A, Barger D, Lodi S, Moreno S, Ramon Arribas J, Pacheco A, Cardoso SW, Chrysos G, Gogos C, Abgrall S, Costagliola D, Meyer L, Seng R, van Sighem A, Reiss P, Muga R, Perez Hoyos S, Braun D, Hauser C, Barrufet P, Leyes M, Tate J, Justice A, Hernan MAet al., 2018, Commonly Prescribed Antiretroviral Therapy Regimens and Incidence of AIDS-Defining Neurological Conditions, Annual Meeting of the Society-of-Epidemiologic-Research, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 102-109, ISSN: 1525-4135

Conference paper

Caniglia EC, Phillips A, Porter K, Sabin CA, Winston A, Logan R, Gill J, Vandenhende M-A, Barger D, Lodi S, Moreno S, Arribas JR, Pacheco A, Cardoso SW, Chrysos G, Gogos C, Abgrall S, Costagliola D, Meyer L, Seng R, van Sighem A, Reiss P, Muga R, Hoyos SP, Braun D, Hauser C, Barrufet P, Leyes M, Tate J, Justice A, Hernán MAet al., 2018, Commonly Prescribed Antiretroviral Therapy Regimens and Incidence of AIDS-Defining Neurological Conditions., J Acquir Immune Defic Syndr, Vol: 77, Pages: 102-109

BACKGROUND: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated 4 neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics. RESULTS: Twenty six thousand one hundred seventy-two individuals initiated efavirenz, 5858 initiated atazanavir, 8479 initiated lopinavir, and 4799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were 1.72 (1.00 to 2.96) for atazanavir, 2.21 (1.38 to 3.54) for lopinavir, and 1.41 (0.61 to 3.24) for darunavir. The respective hazard ratios (95% confidence intervals) for the combined end point were 1.18 (0.74 to 1.88) for atazanavir, 1.61 (1.14 to 2.27) for lopinavir, and 1.36 (0.74 to 2.48) for darunavir. The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age. CONCLUSION: Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our f

Journal article

Ferretti F, Mora-Peris B, Underwood J, Waldman A, Everitt A, Winston Aet al., 2018, Cognitive Impairment in a Clinical Setting, Journal of Acquired Immune Deficiency Syndromes, Vol: 77, Pages: e10-e13, ISSN: 1525-4135

Journal article

Ferretti F, Mora-Peris B, Underwood J, Waldman A, Everitt A, Winston Aet al., 2018, Cognitive Impairment in a Clinical Setting, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 77, Pages: E10-E13, ISSN: 1525-4135

Journal article

Pett SL, Amin J, Horban A, Andrade-Villanueva J, Losso M, Porteiro N, Madero JS, Belloso W, Tu E, Silk D, Kelleher A, Harrigan R, Clark A, Sugiura W, Wolff M, Gill J, Gatell J, Clarke A, Ruxrungtham K, Prazuck T, Kaiser R, Woolley I, Alberto Arnaiz J, Cooper D, Rockstroh JK, Mallon P, Emery S, MARCH study groupet al., 2018, Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study., HIV Med, Vol: 19, Pages: 65-71

OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. METHODS: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. RESULTS: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. CONCLUSIONS: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.

Journal article

De Francesco D, Underwood J, Sabin CA, Winston Aet al., 2018, Associations of non-antiretroviral concomitant medications with cognitive function of people living with HIV (PLWH) and HIV-negative controls, Publisher: SAGE PUBLICATIONS LTD, Pages: A63-A63, ISSN: 1359-6535

Conference paper

Sabin CA, Winston A, Bagkeris E, Mallon PWGet al., 2018, Associations of antiretroviral therapy (ART) with lipid measurements among people with HIV (PWH), Publisher: SAGE PUBLICATIONS LTD, Pages: A51-A51, ISSN: 1359-6535

Conference paper

Le Prevost M, Arenas-Pinto A, Melvin D, Parrott F, Foster C, Ford D, Evangeli M, Winston A, Sturgeon K, Rowson K, Gibb DM, Judd Aet al., 2018, Anxiety and depression symptoms in young people with perinatally acquired HIV and HIV affected young people in England, AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV, Vol: 30, Pages: 1040-1049, ISSN: 0954-0121

Journal article

Van Zoest RA, Underwood J, De Francesco D, Sabin CA, Cole JH, Wit FW, Caan MWA, Kootstra NA, Fuchs D, Zetterberg H, Majoie CBLM, Portegies P, Winston A, Sharp DJ, Gisslén M, Reiss P, Co-morBidity in Relation to AIDS COBRA Collaborationet al., 2017, Structural brain abnormalities in successfully treated HIV infection: associations with disease and cerebrospinal fluid biomarkers., Journal of Infectious Diseases, Vol: 217, Pages: 69-81, ISSN: 0022-1899

Background: Brain structural abnormalities have been reported in persons with HIV (PWH) on suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. Methods: We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PWH on suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years from the Co-morBidity in Relation to AIDS (COBRA) cohort, using multimodal neuroimaging and cerebrospinal fluid (CSF) biomarkers. Results: Compared to controls, PWH had lower grey matter volumes (-13.7 mL [95%-confidence interval -25.1, -2.2 mL]) and fractional anisotropy (-0.0073 [-0.012, -0.0024]), with the largest differences observed in those with prior clinical AIDS. Hypertension and CSF soluble CD14 concentration were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction=0.32 and Pinteraction=0.59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV. Conclusions: The presence of lower grey matter volumes and more white matter microstructural abnormalities in well-treated PWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.

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

Booiman T, Wit FW, Girigorie AF, Maurer I, De Francesco D, Sabin CA, Harskamp AM, Prins M, Franceschi C, Deeks SG, Winston A, Reiss P, Kootstra NAet al., 2017, Terminal differentiation of T cells is strongly associated with CMV infection and increased in HIV-positive individuals on ART and lifestyle matched controls, PLOS ONE, Vol: 12, ISSN: 1932-6203

Journal article

Underwood J, Cole JH, Caan M, De Francesco D, Leech R, van Zoest RA, Su T, Geurtsen GJ, Schmand BA, Portegies P, Prins M, Wit FWNM, Sabin CA, Majoie C, Reiss P, Winston A, Sharp DJet al., 2017, Brain MRI changes associated with poorer cognitive function despite suppressive antiretroviral therapy, 13th International Symposium on the Neurobiology and Neuroendocrinology of Aging, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 125-125, ISSN: 0531-5565

Conference paper

Booiman T, Wit FW, De Francesco D, Sabin CA, Harskamp AM, Prins M, Franceschi C, Winston A, Reiss P, Kootstra NAet al., 2017, Contributors to immune senescence during treated HIV-1 infection, 13th International Symposium on the Neurobiology and Neuroendocrinology of Aging, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 125-126, ISSN: 0531-5565

Conference paper

Nightingale S, Winston A, 2017, Measuring and managing cognitive impairment in HIV, AIDS, Vol: 31, Pages: S165-S172, ISSN: 0269-9370

Journal article

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