Publications by authors named "Marta Boffito"

220 Publications

Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial.

EClinicalMedicine 2022 Feb 14;44:101262. Epub 2022 Jan 14.

Department of Infectious Disease, Imperial College London.

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 19 June to 28 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 optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2.

Funding: This study was co-funded by grants and gifts from the Medical Research Council UKRI (MC_PC_19076), and the National Institute Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, Restore the Earth.
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http://dx.doi.org/10.1016/j.eclinm.2021.101262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759012PMC
February 2022

Weight gain stopping/switch rules for antiretroviral clinical trials.

AIDS 2021 Dec;35(Suppl 2):S183-S188

I-Base, London, UK.

Obesity develops in a substantial number of people initiating and maintaining modern antiretroviral therapy. The comorbidities associated with obesity make significant weight gain and metabolic changes a major consideration in clinical trials studying different regimens' potency and safety. It is as yet unclear what role individual antiretrovirals or classes play in weight gain but the issue is a complex one for clinical trial design, especially when deciding when "too much" weight has been gained, in a context where we do not yet know if switching to alternative regimens will slow, halt or reverse weight gain or metabolic changes. In addition, clinician and trial participant opinion on acceptable weight gain may differ. We offer preliminary guidance for discussion for future antiretroviral clinical trial design.
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http://dx.doi.org/10.1097/QAD.0000000000003092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694575PMC
December 2021

Pharmacokinetic interactions of modern antiretroviral therapy.

AIDS 2021 Dec;35(Suppl 2):S145-S151

Chelsea and Westminster Hospital.

Drug--drug interactions (DDIs) have been a clinical challenge in HIV medicine for over two decades. The newer antiretroviral drugs (ARTs) have significantly fewer DDIs than protease inhibitors and boosted integrase inhibitors (INSTIs). The lower propensity of such newer antiretrovirals (e.g. unboosted integrase inhibitors; doravirine) to cause DDIs, has been largely offset by the ageing cohort of patients with multiple comorbidities, who are taking multiple chronic medicines. Furthermore, the introduction of newly marketed drugs into clinical practice needs to be closely monitored, as the new drugs may be perpetrators of DDIs, leading to a potential change in the efficacy or toxicity of the coadministered antiretrovirals.
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http://dx.doi.org/10.1097/QAD.0000000000002950DOI Listing
December 2021

More evidence for worse COVID-19 outcomes in people with HIV.

Lancet HIV 2021 11 13;8(11):e661-e662. Epub 2021 Oct 13.

Mortimer Market Centre, Central & North West London NHS Trust, London, UK.

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http://dx.doi.org/10.1016/S2352-3018(21)00272-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514199PMC
November 2021

Predictive Value of HIV-Related Versus Traditional Risk Factors for Coronary Atherosclerosis in People Aging with HIV.

AIDS Res Hum Retroviruses 2021 Dec 22. Epub 2021 Dec 22.

HIV/GUM Directorate, Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.

Cardiovascular disease (CVD) is an important cause of morbidity in people living with HIV (PLWH). We compared the predictive value of HIV-related and traditional CVD risk factors to assess which factors best predict the presence of subclinical coronary atherosclerosis in PLWH. This is a cross-sectional study in PLWH over 50 years of age who performed computed tomography coronary artery calcium (CAC) scoring between 2009 and 2019 at Chelsea and Westminster Hospital. The following outcomes were analyzed: CAC = 0 (no calcification), CAC >0 (any calcification), CAC >100 (moderate calcification), and CAC >400 (severe calcification). Univariate and multivariate logistic regression analyses were performed to assess predictors of coronary calcification. A total of 744 patients were included (mean age 56 ± 5.7 years, 94.8% male, 84% white). A CAC >0 was found in 392 (52.7%), CAC >100 in 90 (12.1%), and CAC >400 in 42 (5.6%) subjects. CAC >100 was strongly associated with hypertension [odds ratio, OR: 2.91, (95% confidence interval: 1.93-4.36),  < .001], dyslipidemia [2.71 (1.81-4.06),  < .001], and diabetes [2.53 (1.29-4.96),  = .01]. Regarding HIV-specific factors, a significant association was found with exposure (>6 years) to protease inhibitors [1.67 (1.06-2.61),  = .05], whereas exposure to tenofovir (>8 years) was negatively associated with CAC >100 [0.54 (0.30-0.98),  = .05]. Despite the high prevalence of hypertension (45.4%) only 21.5% were on antihypertensives, whereas only 29.2% of eligible candidates were receiving lipid-lowering drugs for primary prevention of CVD. Traditional cardiometabolic risk factors remain the strongest predictors of coronary atherosclerosis in PLWH as in the general population. These results underscore the importance of optimizing treatment of hypertension and promoting primary prevention strategies that may be underused in PLWH.
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http://dx.doi.org/10.1089/AID.2021.0064DOI Listing
December 2021

A phase IV, open-label three-arm study investigating the impact of a combination of tenofovir disoproxil fumarate/emtricitabine with raltegravir or dolutegravir or elvitegravir/cobicistat on renal function in HIV-1 antiretroviral naïve patients.

HIV Res Clin Pract 2021 Oct 22;22(5):128-139. Epub 2021 Sep 22.

HIV/GUM, St Stephen's AIDS Trust - Chelsea and Westminster NHS Foundation Trust, London, United Kingdom.

Tenofovir DF (TDF) remains one of the preferred backbone agents for naïve HIV patients starting antiretroviral treatment (ART). The impact of TDF on renal function and metabolic parameters may vary by anchor agent. We investigated the impact of TDF in combination with 3 different integrase inhibitors on tubular and glomerular function, and metabolic parameters in ART-naïve patients. Sixty patients with normal renal function were randomised (20 per arm) to TDF/emtricitabine (FTC) plus either raltegravir (RAL) (400 mg b.d.), dolutegravir (DTG) or elvitegravir/cobicistat (EVG/c) for 48 weeks. 57 patients completed the study. Significant increases in RBP/creatinine ratio at week 24 were seen in all arms [RAL +4.7 μg/mmol (CI 0.43 to 8.98,  = 0.032); DTG +4.96 μg/mmol (CI 0.77 to 9.15,  = 0.021); EVG/c +6.95 μg/mmol (CI 2.53 to 11.36,  = 0.002)], although this was not sustained to week 48 in the RAL arm. Similar changes across the arms were observed for urinary α1microglobulin (RAL +6.20 mg/L,  = 0.030; DTG +6.30 mg/L,  = 0.025; EVG/c +8.15 mg/L,  = 0.003). Urinary β2microglobulin significantly increased at week 24 with DTG and EVG/c but remained unchanged in the RAL arm. Glomerular filtration measured with CKD-EPI creatinine-cystatin C increased significantly in the RAL arm at week 24 through 48 but declined modestly in other two arms. Total and LDL cholesterol decreased in the RAL arm, but increased in the EVG/c arm, with no significant changes in the DTG arm. Weight increased significantly from baseline with DTG but not RAL or EVG/c. INSTIs in combination with TDF/FTC impact differently on tubular microproteinuria, eGFR, metabolic markers and weight. Use of TDF/FTC with RAL had the least tubular effects and the most favorable metabolic profile.
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October 2021

FRAX assessment in people ageing with HIV.

HIV Med 2022 Jan 19;23(1):103-108. Epub 2021 Sep 19.

Research and Development Department, Chelsea and Westminster Hospital, London, UK.

Objectives: Current British HIV Association (BHIVA) guidelines recommend the use of FRAX for the routine assessment of bone fracture risk in people living with HIV over 50 years of age every 3 years. Bone mineral density measurement with dual-energy X-ray absorptiometry (DXA) scan is recommended for those with increased fracture risk (FRAX major > 10%). Our objectives were to estimate the prevalence of and risk factors for osteoporosis in a population of PLWH aged > 50 years and assess the utility of FRAX in predicting the presence of DXA-proven osteoporosis in this cohort.

Methods: This was a cross-sectional study of a cohort of PLWH aged > 50 years attending the Chelsea and Westminster Hospital and who had a DXA scan between January 2009 and December 2018. FRAX scores were calculated using the Sheffield algorithm. Multiple regression models and Cohen's kappa values were used to assess risk factors for osteoporosis and agreement between FRAX and DXA scan results, respectively.

Results: In all, 744 patients were included (92.9% male, mean age 56 ± 5 years). The prevalence rates of osteoporosis (at DXA scans) and osteopenia were 12.2% and 63.7%, respectively. FRAX major was > 10% in only two patients, while 90/91 (98.9%) patients with osteoporosis had a normal FRAX score. The presence of osteoporosis was significantly associated with low body mass index and estimated glomerular filtration rate (p < 0.05).

Conclusion: Our results indicate that FRAX scores did not predict the presence of osteoporosis in our population of PLWH over 50 years of age and therefore FRAX scores may not be the appropriate tool to define eligibility to perform DXA scans in PLWH.
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http://dx.doi.org/10.1111/hiv.13170DOI Listing
January 2022

Current Considerations for Clinical Management and Care of People with HIV: Findings from the 11th Annual International HIV and Aging Workshop.

AIDS Res Hum Retroviruses 2021 11 20;37(11):807-820. Epub 2021 Sep 20.

Department of Psychiatry, University of California San Diego, La Jolla, California, USA.

The number of people with HIV (PWH) aged 50 years or older continues to steadily increase. The convergence of age- and HIV-related complications in these individuals presents a challenge for both patients and clinicians alike. New findings continue to emerge, as numerous researchers evaluate the combined impact of these two factors on quality of life, physiological systems, and mental health in PWH. Since its first occurrence in 2009, the International Workshop on HIV and Aging has served as a multidisciplinary meeting to share basic biomedical data, clinical trial results, treatment strategies, and epidemiological recommendations, toward better understanding and outcomes among like-minded scientific professionals. In this article, we share a selection of key findings presented in plenary talks at the 11th Annual International Workshop on HIV and Aging, held virtually from September 30, 2020 to October 2, 2020. We will also address the future directions of HIV and aging research, to further assess how the aging process intersects with chronic HIV.
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http://dx.doi.org/10.1089/AID.2021.0059DOI Listing
November 2021

Strengths and Challenges of Various Models of Geriatric Consultation for Older Adults Living with HIV.

Clin Infect Dis 2021 Aug 6. Epub 2021 Aug 6.

Department of Medicine; University of Colorado - Anschutz Medical Campus; Aurora, CO, USA.

As care of persons living with HIV (PWH) has transitioned from management of opportunistic infections to management of conditions associated with older age, new models of geriatric consultation are needed. The authors, who represent nine different clinics across North America and the United Kingdom, provided their insights on models of geriatric consultation for older individuals living with HIV. Three models of geriatric consultation are delineated: outpatient referral/consultation, combined HIV/geriatric multidisciplinary clinic, and dually-trained providers within one clinical setting. A patient-centered approach and the utilization of expertise across disciplines were universally identified as strengths. Logistical barriers and the reluctance of older PWH to see a geriatric care provider were identified as barriers to implementing these models. Although the optimal model of geriatric consultation depends on a region's resources, there is value in augmenting the training of infectious disease providers to include principles of geriatric care.
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http://dx.doi.org/10.1093/cid/ciab682DOI Listing
August 2021

Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV.

PLoS One 2021 21;16(7):e0253861. Epub 2021 Jul 21.

Department of Infectious Disease, Imperial College London, London, United Kingdom.

Objectives: To investigate the associations of plasma lamivudine (3TC), abacavir (ABC), emtricitabine (FTC) and tenofovir (TFV) concentrations with cognitive function in a cohort of treated people with HIV (PWH).

Methods: Pharmacokinetics (PK) and cognitive function (Cogstate, six domains) data were obtained from PWH recruited in the POPPY study on either 3TC/ABC or FTC/tenofovir disoproxil fumarate (TDF)-containing regimens. Association between PK parameters (AUC0-24: area under the concentration-time curve over 24 hours, Cmax: maximum concentration and Ctrough: trough concentration) and cognitive scores (standardized into z-scores) were evaluated using rank regression adjusting for potential confounders.

Results: Median (IQR) global cognitive z-scores in the 83 PWH on 3TC/ABC and 471 PWH on FTC/TDF were 0.14 (-0.27, 0.38) and 0.09 (-0.28, 0.42), respectively. Higher 3TC AUC0-24 and Ctrough were associated with better global z-scores [rho = 0.29 (p = 0.02) and 0.27 (p = 0.04), respectively], whereas higher 3TC Cmax was associated with poorer z-scores [rho = -0.31 (p<0.01)], independently of ABC concentrations. Associations of ABC PK parameters with global and domain z-scores were non-significant after adjustment for confounders and 3TC concentrations (all p's>0.05). None of the FTC and TFV PK parameters were associated with global or domain cognitive scores.

Conclusions: Whilst we found no evidence of either detrimental or beneficial effects of ABC, FTC and TFV plasma exposure on cognitive function of PWH, higher plasma 3TC exposures were generally associated with better cognitive performance although higher peak concentrations were associated with poorer performance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253861PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294567PMC
November 2021

Remdesivir Versus Standard-of-Care for Severe Coronavirus Disease 2019 Infection: An Analysis of 28-Day Mortality.

Open Forum Infect Dis 2021 Jul 26;8(7):ofab278. Epub 2021 May 26.

Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.

Background: Remdesivir is approved by the US Food and Drug Administration for the treatment of patients hospitalized with coronavirus disease 2019 (COVID-19) and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials.

Methods: This was the final day 28 comparative analysis of data from a phase 3, randomized, open-label study comparing 2 remdesivir regimens (5 vs 10 days, combined for this analysis [remdesivir cohort]) and a real-world retrospective longitudinal cohort study of patients receiving standard-of-care treatment (nonremdesivir cohort). Eligible patients, aged ≥18 years, had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), oxygen saturation ≤94% on room air or required supplemental oxygen, with pulmonary infiltrates. Propensity score matching (up to 1:10 ratio) was used to ensure comparable populations. We assessed day 14 clinical recovery (determined using a 7-point ordinal scale) and day 28 all-cause mortality (coprimary endpoints).

Results: A total of 368 (remdesivir) and 1399 (nonremdesivir) patients were included in the matched analysis. The day 14 clinical recovery rate was significantly higher among the remdesivir versus the nonremdesivir cohort (65.2% vs 57.1%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.16-1.90; = 0.002). The day 28 mortality rate was significantly lower in the remdesivir cohort versus the nonremdesivir cohort (12.0% vs 16.2%; OR, 0.67; 95% CI, 0.47-.95;  = .03).

Conclusions: Remdesivir was associated with significantly higher rates of day 14 clinical recovery, and lower day 28 mortality, compared with standard-of-care treatment in hospitalized patients with COVID-19. These data, taken together, support the use of remdesivir to improve clinical recovery and decrease mortality from SARS-CoV-2 infection.
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http://dx.doi.org/10.1093/ofid/ofab278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244650PMC
July 2021

Evaluation of a Clinic Dedicated to People Aging with HIV at Chelsea and Westminster Hospital: Results of a 10-Year Experience.

AIDS Res Hum Retroviruses 2021 Aug 13. Epub 2021 Aug 13.

HIV Department, Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.

Successful management of HIV infection as a chronic condition has resulted in a demographic shift where the proportion of people living with HIV (PLWH) older than 50 years is steadily increasing. A dedicated clinic to PLWH older than 50 years was established at Chelsea and Westminster Hospital in January 2009 and then extended to HIV services across the directorate. We report the results of a service evaluation reviewing 10 years of activities of this clinic between January 2009 and 2019. We aimed to estimate the prevalence of major noninfectious comorbidities, polypharmacy (≥5 medications), and multimorbidity (≥2 non-HIV-related comorbidities) and describe algorithms devised for use in HIV outpatient clinics across the directorate. A cohort of 744 PLWH older than 50 years attending this service were analyzed (93% male; mean age of 56 ± 5.5 years; 84% white ethnicity); 97.7% were on antiretroviral treatment and 95.9% had undetectable HIV-RNA at the time of evaluation. The most common comorbidities diagnosed were dyslipidemia (50.1%), hypertension (21.5%), mental health disorders (depression and/or anxiety disorders, 15.7%), osteoporosis (12.2%), obesity (11.9%), chronic kidney disease (7.5%), and diabetes (5.8%). Low vitamin D levels were found in 62% of patients [43% with vitamin D deficiency (<40 mmol/liter) and 57% with vitamin D insufficiency (40-70 mmol/liter)]. The overall prevalence of polypharmacy and multimorbidity was 46.6% and 69.3%, respectively. This study showed significant rates of non-HIV-related comorbidities and polypharmacy in PLWH older than 50 years, leading on to the implementation of clinical care pathways and new joint HIV/specialty clinics (cardiology, nephrology, neurology, metabolic, menopause, and geriatric) to improve prevention, diagnosis, and management of major comorbidities in people aging with HIV.
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http://dx.doi.org/10.1089/AID.2021.0083DOI Listing
August 2021

The benefits of tenofovir discontinuation with or without bisphosphonate therapy in osteoporotic people living with HIV.

HIV Med 2021 Oct 13;22(9):816-823. Epub 2021 Jul 13.

HIV/GUM Directorate, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.

Objectives: Treatment with bisphosphonates and discontinuation of tenofovir disoproxil fumarate (TDF) are recommended strategies for managing osteoporosis in people living with HIV (PLHIV). This study aimed to compare the effects on bone mineral density (BMD) of TDF discontinuation with and without bisphosphonate therapy in osteoporotic PLHIV.

Methods: The present study is a retrospective cohort analysis of dual-energy X-ray absorptiometry scan results of PLHIV attending Chelsea and Westminster Hospital HIV clinic between 2009 and 2020. Osteoporotic (T-score < -2.5) patients with ≥ 6 months' TDF exposure were included. Changes in BMD and T-scores at the lumbar spine (LS) and femoral neck (FN) were assessed.

Results: A total of 84 participants were included, of whom 43 discontinued TDF only (TS) and 41 switched from TDF and received bisphosphonates (TS+): 86.9% were male; 77.4% were white; median (interquartile range, IQR) age was 54.8 (51.0-58.5) years; and median (IQR) TDF exposure was 6.5 (3.5-10.4) years. At a median follow-up of 2 years after TDF-discontinuation, mean spine BMD increased significantly in both groups, but bisphosphonate recipients had greater improvements (4.83% vs. 7.79%; P < 0.019); LS T-scores improved significantly but changes were comparable between groups (TS, 0.5 vs. TS+, 0.6; P = 0.270). At the FN, no significant increases in BMD were observed (TS, 3.05% vs. TS+, 2.71%; P = 0.205); T-scores significantly improved in bisphosphonate recipients only (+0.2; P = 0.003). A greater proportion recovered from osteoporosis in the TS+ group (34.9% vs. 43.9%), although differences between groups were not significant (P = 0.503).

Conclusions: Our real-world data indicate that although TDF discontinuation significantly improved bone health in osteoporotic PLHIV, combining bisphosphonates with TDF discontinuation resulted in greater improvements in BMD.
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http://dx.doi.org/10.1111/hiv.13137DOI Listing
October 2021

Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine.

N Engl J Med 2021 09 30;385(13):1172-1183. Epub 2021 Jun 30.

From the Vaccine Institute, St. George's, University of London, and St. George's University Hospitals NHS Foundation Trust (P.T.H., E.P.G., C.C., A.S.F.R.), Chelsea, Westminster Hospital NHS Foundation Trust and Imperial College London (M.B.), the Institute for Global Health, University College London, and Royal Free London NHS Foundation Trust (F.B.), the Centre for Rheumatic Disease, Kings College London (J.G.), the Department of Infectious Diseases, Guy's and St. Thomas' NHS Foundation Trust, MRC Clinical Trials Unit at University College London (A.L.G.), and Renal Services, Epsom and St. Helier University Hospitals NHS Trust (P.A.S.), London, Stockport NHS Foundation Trust, Stepping Hill Hospital, Stockport (D.N.B.), Royal Cornwall Hospitals NHS Trust, Truro (D.B.), Centre for Clinical Infection, South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (D.R.C.), Layton Medical Centre, Blackpool (R.C.), Lakeside Healthcare Research, Lakeside Surgeries, Corby (A. Heer), University Hospitals of Morecambe Bay NHS Foundation Trust, Kendal (A. Higham), Accelerated Enrollment Solutions, Synexus Hexham Dedicated Research Site, Hexham General Hospital, Hexham (S.I.), Accelerated Enrollment Solutions, Synexus Thames Valley Dedicated Research Site, Reading (A.J.), Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich (C.J., J.T.), Salford Royal NHS Foundation Trust, Northern Care Alliance, Salford (P.A.K.), Accelerated Enrollment Solutions, Synexus Midlands Dedicated Research Site, Birmingham (C.K.), Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast and Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast (D.F.M.), Accelerated Enrollment Solutions, Synexus Merseyside Dedicated Research Site, Liverpool (A.M.), Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, and Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford (A.M.M.), St. James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds (J.M.), the Adam Practice, Poole (P.M.), University Hospital Southampton NHS Foundation Trust, Southampton (P.M.), Accelerated Enrollment Solutions, Synexus Glasgow Dedicated Research Site (I.M.), and MRC-University of Glasgow Centre for Virus Research and Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde (E.C.T.), Glasgow, Accelerated Enrollment Solutions, Synexus Wales Dedicated Research Site, Cardiff (H.N.), the School of Medical Sciences, Bangor University, and Betsi Cadwaladr University Health Board, Bangor (O.O.), the Division of Epidemiology and Public Health, University of Nottingham, Nottingham (J.P.), Haywood Hospital, Midlands Partnership NHS Foundation Trust, Stafford (J.P.), Accelerated Enrollment Solutions, Synexus Lancashire Dedicated Research Site, Chorley (C.H.P.), the National Institute for Health Research Patient Recruitment Centre and Bradford Teaching Hospitals NHS Foundation Trust, Bradford (D.S.), Royal Devon and Exeter Hospital, Exeter (R.P.S.), East Suffolk, North Essex NHS Foundation Trust and University of Essex, Colchester (R.S.), Aberdeen Royal Infirmary, NHS Grampian, and Aging Clinical and Experimental Research Group, University of Aberdeen, Aberdeen (R.L.S.), and Accelerated Enrollment Solutions, Synexus Manchester Dedicated Research Site, Manchester (M.E.V.) - all in the United Kingdom; and Novavax, Gaithersburg, MD (G.A., I.C., F.D., G.G., J.R., A.R., K.S., S.T.).

Background: Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population.

Methods: In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-μg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline.

Results: A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups.

Conclusions: A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16.).
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http://dx.doi.org/10.1056/NEJMoa2107659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262625PMC
September 2021

Factors associated with overweight/obesity in a cohort of people living with HIV over 50 years of age.

AIDS Care 2021 Jun 4:1-3. Epub 2021 Jun 4.

HIV/GUM Directorate, Chelsea and Westminster Hospital Foundation Trust, London, UK.

Changes in body weight in people living with HIV vary by regimen components, timing of therapy introduction (naive, switch) and demographic factors. Our objective was to evaluate weight change and factors associated in an ageing cohort of treated subjects with HIV at Chelsea and Westminster Hospital. We found that the prevalence of obesity was similar to general population and was associated with a number of health conditions, which increase metabolic risk.
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http://dx.doi.org/10.1080/09540121.2021.1935438DOI Listing
June 2021

Pharmacokinetic/pharmacodynamic investigation of raltegravir with or without lamivudine in the context of HIV-1 pre-exposure prophylaxis (PrEP).

J Antimicrob Chemother 2021 07;76(8):2129-2136

Guys and St Thomas' NHS Foundation Trust and King's College London, London, UK.

Background: To characterize their potential use in pre-exposure prophylaxis (PrEP) we compared the pharmacokinetics of raltegravir and lamivudine in genital tissue against ex vivo tissue infection with HIV-1.

Methods: Open-label trial of 36 HIV-negative females and males randomized to 7 days raltegravir 400 mg twice daily and 7 days raltegravir 400 mg+lamivudine 150 mg twice daily (after washout), or vice versa. Blood, saliva, rectal fluid, rectal tissue, vaginal fluid and vaginal tissue were sampled at baseline and on and off PrEP during a total of 12 days, for pharmacokinetics and antiviral activity via ex vivo HIV-1BaL challenge. Ex vivo infectivity was compared with baseline. The trial has been registered in https://clinicaltrials.gov/ with the identifier NCT03205566.

Results: Steady state for both drugs was reached by day 4. Dosing with raltegravir alone provided modest ex vivo HIV protection with higher drug levels in rectal tissue and vaginal tissue than in plasma on and off PrEP. Off PrEP, plasma and vaginal concentrations declined rapidly, while persisting in the rectum. On PrEP, the highest lamivudine concentrations were in the rectum, followed by vaginal tissue then plasma. Lamivudine washout was rapid in plasma, while persisting in the rectum and vagina. Raltegravir/lamivudine increased ex vivo protection on and off PrEP compared with raltegravir alone, reaching maximum protection at day 2 in rectal tissue and at day 8 in vaginal tissue.

Conclusions: Raltegravir 400 mg+lamivudine 150 mg showed high levels of ex vivo HIV protection, associated with high drug concentrations persisting after discontinuation in vaginal and rectal compartments, supporting further investigation of these agents for PrEP.
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http://dx.doi.org/10.1093/jac/dkab136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325523PMC
July 2021

Feasibility randomized-controlled trial of online acceptance and commitment therapy for painful peripheral neuropathy in people living with HIV: The OPEN study.

Eur J Pain 2021 08 26;25(7):1493-1507. Epub 2021 Mar 26.

Department of Psychology, Uppsala University, Uppsala, Sweden.

Background: Neuropathic pain negatively affects quality of life among people living with HIV (PLWH). This study examined the feasibility of conducting a full-scale randomized-controlled trial of online acceptance and commitment therapy ("ACT OPEN") for neuropathic pain in PLWH.

Methods: Using a parallel-groups design, thirty-eight participants were randomized to ACT OPEN or a waitlist control (2:1). Participants completed standard self-report outcome measures at baseline, and two- and five-months post-randomization. Participants were aware of their allocation, but assessment was blinded.

Results: Twenty-five participants were randomized to ACT OPEN and 13 to the control (of 133 referrals). ACT OPEN completion was 69% and two-month trial retention was 82%. Treatment credibility and satisfaction scores for ACT OPEN were comparable to scores reported in previous trials of cognitive-behavioural treatments for pain. Four adverse events were reported during the study, including one serious adverse event; all of these were unrelated to the research procedures. Small to moderate effects and 95% confidence intervals suggest that the true effect may favour ACT OPEN for improvements in pain intensity/interference and depression.

Conclusions: A full-scale RCT of online ACT for pain management in PLWH may be feasible with refinements to trial design to facilitate recruitment.

Significance: Research on pain management in people living with HIV has primarily focused on pharmacological treatments with limited success. This is the first study to show the potential feasibility of a psychological treatment based on acceptance and commitment therapy delivered online and tailored for pain management in people with HIV ("ACT OPEN"). ACT OPEN may be a promising treatment in this population and further evaluation in a full-scale randomized-controlled trial appears warranted.

Trial Registration: The trial was registered (clinicaltrials.gov; NCT03584412).
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http://dx.doi.org/10.1002/ejp.1762DOI Listing
August 2021

Agreement between self-reported and objective measures of sleep in people with HIV and lifestyle-similar HIV-negative individuals.

AIDS 2021 06;35(7):1051-1060

Minneapolis Veterans Affairs Healthcare System.

Objectives: The aim of this study was to evaluate the agreement between self-reported sleep measures and insomnia with objectively measured sleep parameters in people with HIV (PWH) and HIV-negative individuals.

Design: A cross-sectional analysis of PWH and lifestyle-similar HIV-negative individuals.

Methods: Self-reported measures included time spent in bed, sleep onset latency and a validated insomnia questionnaire. Objective measures were assessed via 7-days/nights of actigraphy data to determine average and intra-individual variability of several sleep measures (including time spent in bed and onset latency). Spearman's correlation coefficient and Cohen's κ were used to assess the agreement between self-reported and actigraphy-assessed measures. Associations between insomnia and actigraphy-assessed sleep parameters were evaluated using partial least-square discriminant analysis (PLS-DA).

Results: We found fair correlation between self-reported and actigraphy-assessed time spent in bed in 342 PWH (rs = 0.46) and 119 HIV-negative individuals (rs = 0.48). Among PWH, the correlation did not differ by age, education, depressive symptoms and self-reported insomnia (all P > 0.05), but was stronger in men (P = 0.05) and in those with a BMI of at least 25 kg/m2 (P < 0.001). Agreement between self-reported and actigraphy-assessed sleep onset latency was poor in both PWH (κ = 0.002, P = 0.49) and HIV-negative individuals (κ = 0.009, P = 0.65). According to PLS-DA, self-reported insomnia most strongly correlated with intra-individual variability of sleep duration, movement index and efficiency.

Conclusion: We report poor-to-fair agreement between self-reported and actigraphy-assessed sleep measures in PWH. Insomnia symptoms correlated with regularity of sleep duration, quality and efficiency. These findings highlight the importance of both patient-reported and objective measures of daily sleep variation, for better understanding sleep disorders in PWH.
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http://dx.doi.org/10.1097/QAD.0000000000002852DOI Listing
June 2021

The evidence for using tenofovir disoproxil fumarate plus lamivudine as a nucleoside analogue backbone for the treatment of HIV.

J Virus Erad 2021 Mar 29;7(1):100028. Epub 2021 Jan 29.

Chelsea and Westminster Hospital, London, UK.

This article evaluates the evidence supporting use of the tenofovir disoproxil fumarate (TDF) plus lamivudine (3 ​TC) combination as a dual nucleoside backbone within a triple drug antiretroviral regimen. Key trials that assess the relative efficacy, safety and resistance profile of 3 ​TC and emtricitabine (FTC) are discussed. Clinical use of 3 ​TC and FTC with two tenofovir prodrugs -TDF and tenofovir alafenamide (TAF) - is presented. Recommendations from various international guidelines for the construction of triple and emerging dual regimens are summarised. In conclusion, data suggest the therapeutic equivalence of 3 ​TC and FTC, especially when 3 ​TC is combined with TDF.
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http://dx.doi.org/10.1016/j.jve.2021.100028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868802PMC
March 2021

Sleep health and cognitive function among people with and without HIV: the use of different machine learning approaches.

Sleep 2021 08;44(8)

Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA.

Study Objectives: We investigated associations between actigraphy-assessed sleep measures and cognitive function in people with and without HIV using different analytical approaches to better understand these associations and highlight differences in results obtained by these approaches.

Methods: Cognitive and 7-day/night actigraphy data were collected from people with HIV (PWH) and lifestyle-similar HIV-negative individuals from HIV and sexual health clinics in the United Kingdom/Ireland. A global cognitive T-score was obtained averaging the standardized individual cognitive test scores accounting for sociodemographics. Average and SD of 11 sleep measures over 7 days/nights were obtained. Rank regression, partial least-squares (PLS) regression, random forest, sleep dimension construct, and latent class analysis (LCA) were applied to evaluate associations between global T-scores and sleep measures.

Results: In 344 PWH (median age 57 years, 86% males), average sleep duration, efficiency, and wake after sleep onset were not associated with global T-scores according to rank regression (p = 0.51, p = 0.09, p = 0.16, respectively). In contrast, global T-scores were associated with average and SD of length of nocturnal awakenings, SD of maintenance efficiency, and average out-of-bed time when analyzed by PLS regression and random forest. No associations were found when using sleep dimensions or LCA. Overall, findings observed in PWH were similar to those seen in HIV-negative individuals (median age 61 years, 67% males).

Conclusions: Using multivariable analytical approaches, measures of sleep continuity, timing, and regularity were associated with cognitive performance in PWH, supporting the utility of newer methods of incorporating multiple standard and novel measures of sleep-wake patterns in the assessment of health and functioning.
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http://dx.doi.org/10.1093/sleep/zsab035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361343PMC
August 2021

Sleep Disorders in Human Immunodeficiency Virus: A Substudy of the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Study.

Open Forum Infect Dis 2021 Jan 18;8(1):ofaa561. Epub 2020 Nov 18.

Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA).

Methods: Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires.

Results: We enrolled 357 PWH (246 >50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls >50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2-12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia.

Conclusions: Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population.
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http://dx.doi.org/10.1093/ofid/ofaa561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781463PMC
January 2021

Correlation between computerised and standard cognitive testing in people with HIV and HIV-negative individuals.

AIDS Care 2021 10 28;33(10):1296-1307. Epub 2020 Dec 28.

Division of Infectious Diseases, Imperial College London, London, UK.

We investigated the correlations and agreement between cognitive assessments made using a computerised (CogState™, six domains) and a standard pen-and-paper battery (five domains) in PWH and lifestyle-similar HIV-negative individuals. Demographically adjusted domain and global -scores were obtained and used to define cognitive impairment according to the multivariate normative comparison (MNC) criteria. Correlations between -scores and the agreement between the classifications of cognitive impairment obtained from the two batteries were assessed using the Spearman's rank correlation and Cohen's , respectively. The correlation between global -scores from the two batteries was 0.52 (95% CI 0.44-0.60) in PWH and 0.45 (0.29-0.59) in controls (=0.38 for their difference). Correlations were generally stronger between domains within the same battery than between those from different batteries. The agreement between the two batteries in classifying individuals as cognitively impaired or not impaired was fair in PWH (=0.24) and poor in HIV-negative individuals (=-0.02). The moderate correlation between overall cognitive function and the modest agreement between binary classifications of cognitive impairment obtained from two different batteries indicate the two batteries may assess slightly different components of cognition.
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http://dx.doi.org/10.1080/09540121.2020.1865518DOI Listing
October 2021

Toward Consensus on Correct Interpretation of Protein Binding in Plasma and Other Biological Matrices for COVID-19 Therapeutic Development.

Clin Pharmacol Ther 2021 07 21;110(1):64-68. Epub 2020 Nov 21.

Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.

The urgent global public health need presented by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has brought scientists from diverse backgrounds together in an unprecedented international effort to rapidly identify interventions. There is a pressing need to apply clinical pharmacology principles and this has already been recognized by several other groups. However, one area that warrants additional specific consideration relates to plasma and tissue protein binding that broadly influences pharmacokinetics and pharmacodynamics. The principles of free drug theory have been forged and applied across drug development but are not currently being routinely applied for SARS-CoV-2 antiviral drugs. Consideration of protein binding is of critical importance to candidate selection but requires correct interpretation, in a drug-specific manner, to avoid either underinterpretation or overinterpretation of its consequences. This paper represents a consensus from international researchers seeking to apply historical knowledge, which has underpinned highly successful antiviral drug development for other viruses, such as HIV and hepatitis C virus for decades.
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http://dx.doi.org/10.1002/cpt.2099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359231PMC
July 2021

Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis.

Br J Clin Pharmacol 2021 04 1;87(4):2078-2088. Epub 2020 Dec 1.

Department of Molecular and Clinical Pharmacology, Materials Innovation Factory, University of Liverpool, Liverpool, UK.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic and urgent treatment and prevention strategies are needed. Nitazoxanide, an anthelmintic drug, has been shown to exhibit in vitro activity against SARS-CoV-2. The present study used physiologically based pharmacokinetic (PBPK) modelling to inform optimal doses of nitazoxanide capable of maintaining plasma and lung tizoxanide exposures above the reported SARS-CoV-2 EC .

Methods: A whole-body PBPK model was validated against available pharmacokinetic data for healthy individuals receiving single and multiple doses between 500 and 4000 mg with and without food. The validated model was used to predict doses expected to maintain tizoxanide plasma and lung concentrations above the EC in >90% of the simulated population. PopDes was used to estimate an optimal sparse sampling strategy for future clinical trials.

Results: The PBPK model was successfully validated against the reported human pharmacokinetics. The model predicted optimal doses of 1200 mg QID, 1600 mg TID and 2900 mg BID in the fasted state and 700 mg QID, 900 mg TID and 1400 mg BID when given with food. For BID regimens an optimal sparse sampling strategy of 0.25, 1, 3 and 12 hours post dose was estimated.

Conclusion: The PBPK model predicted tizoxanide concentrations within doses of nitazoxanide already given to humans previously. The reported dosing strategies provide a rational basis for design of clinical trials with nitazoxanide for the treatment or prevention of SARS-CoV-2 infection. A concordant higher dose of nitazoxanide is now planned for investigation in the seamless phase I/IIa AGILE trial.
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http://dx.doi.org/10.1111/bcp.14619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056737PMC
April 2021

HIV Antivirals Affect Endothelial Activation and Endothelial-Platelet Crosstalk.

Circ Res 2020 11 1;127(11):1365-1380. Epub 2020 Oct 1.

Department of Infectious Disease (A.O.L., M.N., B.G., M.B.), Imperial College London, London, United Kingdom.

Rationale: People living with HIV on effective antiretroviral therapy are at increased risk of cardiovascular complications, possibly due to off-target drug effects. Some studies have associated antiretroviral therapy with increased risk of myocardial infarction and endothelial dysfunction, but a link between endothelial function and antiretrovirals has not been established.

Objective: To determine the effects of antiretrovirals in common clinical use upon in vitro endothelial function to better understand cardiovascular risk in people living with HIV.

Methods And Results: Human umbilical cord vein endothelial cells or human coronary artery endothelial cells were pretreated with the antiretrovirals abacavir sulphate (ABC), tenofovir disoproxil fumarate, or tenofovir alafenamide. Expression of adhesion molecules, ectonucleotidases (CD39 and CD73), tissue factor (TF), endothelial-derived microparticle (EMP) numbers and phenotype, and platelet activation were evaluated by flow cytometry. TF and ectonucleotidase activities were measured using colourimetric plate-based assays. ABC-treated endothelial cells had higher levels of ICAM (intercellular adhesion molecule)-1 and TF expression following TNF (tumor necrosis factor)-α stimulation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide treatment gave rise to greater populations of CD39CD73 cells. These cell surface differences were also observed within EMP repertoires. ABC-treated cells and EMP had greater TF activity, while tenofovir disoproxil fumarate- and tenofovir alafenamide-treated cells and EMP displayed higher ectonucleotidase activity. Finally, EMP isolated from ABC-treated cells enhanced collagen-evoked platelet integrin activation and α-granule release.

Conclusions: We report differential effects of antiretrovirals used in the treatment of HIV upon endothelial function. ABC treatment led to an inflammatory, prothrombotic endothelial phenotype that promoted platelet activation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide conferred potentially cardioprotective properties associated with ectonucleotidase activity. These observations establish a link between antiretrovirals and specific functional effects that provide insight into cardiovascular disease in people living with HIV.
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http://dx.doi.org/10.1161/CIRCRESAHA.119.316477DOI Listing
November 2020

Rapid ART start in early HIV infection: Time to viral load suppression and retention in care in a London cohort.

HIV Med 2020 10 1;21(9):613-615. Epub 2020 Sep 1.

Chelsea & Westminster Hospital NHS Foundation Trust, London, UK.

Objectives: Rapid antiretroviral therapy (ART) initiation is recommended in early HIV infection (EHI), even in the absence of baseline viral resistance test result. We analysed time to viral suppression according to ART regimen started in a cohort of patients diagnosed with EHI.

Methods: Clinical records of individuals consecutively diagnosed with EHI between July 2016-June 2018 were reviewed. The distribution of clinical, virological and immunological factors was compared in treatment groups using the Mann-Whitney U-test.

Results: 262 individuals (97% MSM) were diagnosed with EHI. 58% of patients agreed to start ART within 14 days of diagnosis. Tenofovir-based combinations were prescribed to all patients. DRV/b was the most commonly prescribed third agent (78%), when genotypic resistance testing was not available at time of ART choice. Switching to INSTI was encouraged once VRT became available and 27% switched from DRV/b to INSTI (mainly RAL) within 28 days from ART start. Those receiving INSTI were more likely to have a baseline viral load exceeding 1 million HIV-1 RNA copies/mL compared with those starting with DRV/b. Rapid start with INSTI regimens resulted in quicker viral suppression than when DRV/b was chosen in EHI, even when that was subsequently switched to INSTI. Retention in care following rapid ART start was achieved by all patients at 24 weeks.

Conclusions: Starting an INSTI-based ART combination was associated with quicker viral suppression than when a protease inhibitor-based combination was chosen. No differences in the achievement of viral suppression or in retention in care were observed.
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http://dx.doi.org/10.1111/hiv.12900DOI Listing
October 2020

The predictors of pain extent in people living with HIV.

AIDS 2020 11;34(14):2071-2079

Department of Infectious Disease, Imperial College London, London, UK.

Objective: To investigate the prevalence of widespread pain among people with HIV (PWH) and describe associations with antiretroviral therapy (ART) and markers of HIV disease stage.

Design: Cross-sectional analysis of cohort study in the United Kingdom and Ireland.

Methods: Pain information was collected during the baseline visit (conducted from 2013 to 2015) through a self-completed manikin identifying pain at 15 sites from five body regions. Pain was classified as widespread if reported at at least four regions and at least seven sites, or regional otherwise. Chi-squared tests, Kruskal-Wallis tests and ordinal logistic regression were used to consider associations between pain extent and sociodemographic and HIV-related factors.

Results: Among the 1207 participants (614 PWH ≥ 50 years, 330 PWH < 50 years, 263 HIV-negative controls ≥50 years), pain was most commonly reported at the upper (left: 28.9%, right: 28.0%) and lower (left: 25.7%; right: 24.5%) leg, upper (18.6%) and lower (29.7%) back and shoulders (left: 16.0%; right: 16.8%). Widespread pain was more commonly reported in PWH than in HIV-negative controls (PWH ≥ 50 years: 18.7%; PWH < 50 years: 12.7%; HIV-negative ≥50 years: 9.5%) with regional pain reported in 47.6, 44.8 and 49.8%, respectively (global P = 0.001). In multivariable analyses, pain extent was greater in those with lower educational attainment, those exposed to more ART drugs, and those with a higher current CD4 cell count but longer exposure to immunosuppression.

Conclusion: Widespread pain is commonly reported in PWH and is associated with longer duration of exposure to HIV, immunosuppression and ART. Our findings call for greater awareness, and interventions to support the management, of pain in PWH.
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http://dx.doi.org/10.1097/QAD.0000000000002660DOI Listing
November 2020

Multimodality assessment of sleep outcomes in people living with HIV performed using validated sleep questionnaires.

Int J STD AIDS 2020 09;31(10):996-1003

Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.

Studies conducted in people living with HIV (PLHIV) report high rates of sleep disturbance, without a clear explanation as to cause or effect. Therefore, we proposed use of multiple validated questionnaires that would allow a more comprehensive evaluation of sleep quality in PLHIV. We administered eight validated sleep and wellbeing questionnaires, recording different aspects of sleep in order to provide a comprehensive description of sleep quality, quantity, daytime functioning, wakefulness, and general wellbeing. Associations with demographics and clinical data were analyzed by univariable/multivariable analyses. Of 254 subjects 99% were male (98% men who have sex with men), 88% white, mean age 41 (SD ± 9.9) years, HIV duration eight years (SD ± 6.3), 94% were on antiretroviral therapy, mean CD4 cell count was 724 cells/mm, 81% had HIV RNA<40 copies/ml, 72% were university educated, and 60% used 'chemsex' drugs. Almost half (45%) reported poor sleep quality, 22% insomnia, 21% daytime sleepiness, and 33% fatigue. As individual factors, HIV duration ≥10 years, anxiety, depression, and recreational drug use were associated with poor quality sleep, fatigue, and poorer functional outcomes (p ≤ 0.05). The prevalence of sleep disturbance was high in our cohort of PLHIV. Sleep disturbance was associated with longer duration of HIV infection, depression, anxiety, and recreational drug use.
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http://dx.doi.org/10.1177/0956462420941693DOI Listing
September 2020

Comorbidity indices in people with HIV and considerations for coronavirus disease 2019 outcomes.

AIDS 2020 10;34(12):1795-1800

Institute for Global Health, University College London.

Objective: To determine comorbidity indices in people with HIV (PWH) and lifestyle-similar HIV-negative controls.

Design: Cross-sectional analysis of the Pharmacokinetic and clinical Observations in PeoPle over fiftY cohort study in the United Kingdom and Ireland.

Methods: The Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index and the Comorbidity Burden Index were compared between older PWH and HIV-negative controls using the Mann-Whitney U test; the magnitude of the difference between groups was quantified using the r effect size.

Results: The 699 PWH and 304 HIV-negative controls were predominantly male (87.5% vs. 64.0%), white (86.3% vs. 90.0%) and had median ages of 57 and 58 years, respectively. Among PWH, the median (interquartile range) CD4 T-cell count was 624 (475, 811) cells/μl; 98.7% were on antiretroviral therapy. The median (interquartile range) ECI was 0 (0, 8) and 0 (-3, 1), Charlson Comorbidity Index was 2 (1, 5) and 1 (0, 1) and Comorbidity Burden Index 8.6 (2.2, 16.8) and 5.9 (0.6, 10.8), respectively. While all three indices were significantly higher in PWH than in controls (P < 0.001 for each), the magnitude of the differences between the two groups were small to medium, with effect sizes (95% confidence interval) of 0.21 (0.16, 0.27), 0.38 (0.32, 0.42) and 0.18 (0.11, 0.23), respectively.

Conclusion: These three comorbidity indices are higher in PWH compared with HIV-negative controls, although the magnitude of differences between groups were small. Differences in the ECI, reportedly associated with poorer coronavirus disease 2019 outcomes, were driven by more individuals with HIV being within the higher end of the range.
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http://dx.doi.org/10.1097/QAD.0000000000002606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493769PMC
October 2020
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