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Aung HL, Alagaratnam J, Chan P, et al., 2023, Cognitive Health in Persons With Human Immunodeficiency Virus: The Impact of Early Treatment, Comorbidities, and Aging., J Infect Dis, Vol: 227, Pages: S38-S47
Henderson M, Pepper N, Bawa M, et al., 2023, Cerebrospinal fluid virology in people with HIV., HIV Med
OBJECTIVE: Our objectives were to investigate the recent frequency of cerebrospinal fluid (CSF) HIV RNA escape and other CSF viral nucleic acid detection in people with HIV with neurological symptoms and to assess associated clinical factors. METHOD: This was a retrospective cohort analysis of people with HIV who underwent CSF examination for clinical indications between 2017 and 2022. Individuals were identified from pathology records, and clinical data were recorded. CSF HIV RNA escape was defined as CSF HIV RNA concentrations greater than in plasma. CSF viral screen included herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and JC virus. When cases were detected in five or more people with HIV, associated clinical factors were assessed using linear regression modelling. RESULTS: CSF HIV RNA escape was observed in 19 of 114 individuals (17%) and was associated with the presence of HIV drug resistance mutations and non-integrase strand transfer inhibitor-based antiretroviral therapy (p < 0.05 for all) when compared to people with HIV without escape. Positive viral nucleic acid testing included EBV (n = 10), VZV (3), CMV (2), HHV-6 (2) and JC virus (4). Detectable CSF EBV was not considered related to neurological symptoms and was associated with concomitant CSF infections in eight of ten individuals and with CSF pleocytosis, previous AIDS, lower nadir and current CD4 T-cell count (p < 0.05 for all). CONCLUSION: In people with HIV with neurological symptoms, the frequency of CSF HIV RNA escape remains similar to that in historical reports. Detectable EBV viral nucleic acid in the CSF was observed frequently and, in the absence of clinical manifestations, may be a consequence of CSF pleocytosis.
Nikolaichuk M, Mocroft A, Wandeler G, et 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
Szubert AJ, Pollock KM, Cheeseman HM, et 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
Fidler S, Fox J, Tipoe T, et 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.
Waters L, Winston A, Reeves I, et al., 2022, BHIVA guidelines on antiretroviral treatment for adults living with HIV-1 2022, HIV MEDICINE, Vol: 23, Pages: 3-115, ISSN: 1464-2662
Yu X, Lobo JDD, Sundermann E, et al., 2022, 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
Elliott T, Cheeseman HM, Evans AB, et 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
Waters L, Winston A, Reeves I, et 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
Heskin J, Belfield A, Milne C, et 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
Ogbe A, Pace M, Bittaye M, et al., 2022, Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV, JCI INSIGHT, Vol: 7
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Ryom L, De Miguel R, Cotter AG, et 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
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Pollock KM, Cheeseman HM, Szubert AJ, et 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
Ulfhammer G, Eden A, Antinori A, et 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
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- Citations: 6
Arenas-Pinto A, Judd A, Melvin D, et al., 2022, Learning and memory function in young people with and without perinatal HIV in England., PLoS One, Vol: 17
Learning and memory are important for successful education and career progression. We assess these functions in young people (YP) with perinatal HIV (PHIV) (with or without a previous AIDS-defining illness) and a comparable group of HIV-negative YP. 234 PHIV and 68 HIV-negative YP completed 9 tests; 5 National Institutes of Health (NIH) Toolbox tests (2 executive function, 1 speed of information processing, 2 memory); 2 Hopkins Verbal Learning Test Revised (HVLT-R) (learning (L), delayed recall (R)), and 2 verbal application measures. Z-scores for each test were calculated using normative data and averaged by domain where appropriate. The effect of predictors on test scores in the three domains with the lowest z-scores were analysed using linear regression. 139(59%) and 48(71%) PHIV and HIV-negative YP were female, 202(86%) and 52(76%) Black, and median age was 19 [17, 21] and 18 [16, 21] years respectively. 55(24%) PHIV had a previous Center for Disease Control and Prevention (CDC) class C AIDS-defining diagnosis (PHIV/C). For HVLT-R, there was a trend towards PHIV/C YP having the lowest mean z-scores (L -1.5 (95% CI -1.8,-1.2), R -1.7 (-2.0,-1.4)) followed by PHIV without a CDC C diagnosis (L -1.3 (-1.4,-1.1), R -1.4 (-1.5,-1.2)) and then the HIV-negative group (L -1.0 (-1.3,-0.7), R -1.1 (-1.3,-0.8)); all were greater than 1 SD below the reference mean. The same trend was seen for verbal application measures; however, z-scores were within 1 SD below the reference mean. NIH Toolbox tests were similar for all groups. In multivariable analyses PHIV/C and Black ethnicity predicted lower HVLT-R scores. Black ethnicity also predicted lower executive function scores, however each year increase in age predicted higher scores. In conclusion, cognitive performance in verbal learning and recall fell below population normative scores, and was more pronounced in PHIV/C, supporting wider findings that earlier antiretroviral therapy initiation, before the occurrence of AIDS-def
Thakrar J, Rae C, Cercignani M, et al., 2021, Brain connectivity and patient-reported outcomes in people with human immunodeficiency virus with symptoms of insomnia, switching integrase inhibitor-based antiretroviral therapy, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S160-S161, ISSN: 0924-977X
Alagaratnam J, De Francesco D, Zetterberg H, et al., 2021, 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
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Chan TY-H, De Zan V, Gregg A, et al., 2021, The symptomatology of cerebrospinal fluid HIV RNA escape: a large case-series, AIDS, Vol: 35, Pages: 2341-2346, ISSN: 0269-9370
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Morphett K, Puljevic C, Boyd M, et al., 2021, A PRAGMATIC RANDOMISED PARTIAL CROSSOVER CLINICAL TRIAL OF NICOTINE VAPORISERS ADDED TO STANDARD CARE FOR SMOKING CESSATION AND RELAPSE PREVENTION AMONG PRIORITY POPULATIONS WITH COMORBIDITIES, Publisher: WILEY, Pages: S15-S15, ISSN: 0959-5236
Mora-Peris B, Keegan MR, Penchala SD, et al., 2021, Cerebral function parameters in people with HIV switching integrase inhibitors: a randomized controlled trial, HIV RESEARCH & CLINICAL PRACTICE, Vol: 22, Pages: 151-159, ISSN: 2578-7489
Alagaratnam J, Sabin C, Garvey LJ, et al., 2021, Evaluating virological outcomes in people with HIV on stable ART with reduced frequency of HIV viral load monitoring during the COVID-19 pandemic, Publisher: WILEY, Pages: 42-43, ISSN: 1464-2662
Campbell L, Barbini B, Burling K, et al., 2021, Safety of Tenofovir Alafenamide in People With HIV Who Experienced Proximal Renal Tubulopathy on Tenofovir Disoproxil Fumarate, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 88, Pages: 214-219, ISSN: 1525-4135
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Alagaratnam J, Stohr W, Toombs J, et al., 2021, No evidence of neuronal damage as measured by neurofilament light chain in a HIV cure study utilising a kick-and-kill approach, JOURNAL OF VIRUS ERADICATION, Vol: 7, ISSN: 2055-6640
Asad H, Collins IJ, Goodall RL, et al., 2021, Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK, HIV Medicine, Vol: 22, Pages: 631-640, ISSN: 1464-2662
OBJECTIVES: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. METHODS: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. RESULTS: At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/μL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/μL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. CONCLUSIONS: Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality.
Pasternak AO, Vroom J, Kootstra NA, et al., 2021, Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell- associated HIV RNA and DNA levels compared to protease inhibitor-based therapy, eLife, Vol: 10, Pages: 1-21, ISSN: 2050-084X
Background:It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).Methods:CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART.Results:In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj = 0.048 and padj = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals.Conclusions:All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, whi
Caby F, Caby F, Guiguet M, et al., 2021, CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies (vol 73, pg 50, 2021), CLINICAL INFECTIOUS DISEASES, Vol: 73, Pages: 563-563, ISSN: 1058-4838
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Hunt M, Khosla R, Sabin C, et al., 2021, Mito-Flow: a novel assay for T-cell mitochondrial dysfunction in ageing and HIV, Publisher: WILEY, Pages: 4-4, ISSN: 1464-2662
Frater J, Ewer KJ, Ogbe A, et al., 2021, Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial, The Lancet HIV, Vol: 8, Pages: e474-e485, ISSN: 2352-3018
BackgroundData on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV.MethodsIn this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18–55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per μL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4–6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing.FindingsBetween Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2–49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per μL (IQR 573·5–859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime va
De Francesco D, Wang X, Dickinson L, et al., 2021, Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV, PLoS One, Vol: 16, Pages: 1-10, ISSN: 1932-6203
ObjectivesTo 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).MethodsPharmacokinetics (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.ResultsMedian (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.ConclusionsWhilst 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.
Alagaratnam J, von Widekind S, De Francesco D, et al., 2021, Correlation between CSF and blood neurofilament light chain protein: A systematic review and meta-analysis, BMJ Open Neurology, Vol: 3, ISSN: 2632-6140
Objective To assess the overall pooled correlation coefficient estimate between cerebrospinal fluid (CSF) and blood neurofilament light (NfL) protein.Methods We searched Medline, Embase and Web of Science for published articles, from their inception to 9 July 2019, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies reporting the correlation between CSF and blood NfL in humans were included. We conducted a random-effects meta-analysis to calculate the overall pooled correlation coefficient estimate, accounting for correlation technique and assay used. Heterogeneity was assessed using the I2 statistic test. In sensitivity analyses, we calculated the pooled correlation coefficient estimate according to blood NfL assay: single-molecule array digital immunoassay (Simoa), electrochemiluminescence (ECL) assay or ELISA.Results Data were extracted from 36 articles, including 3961 paired CSF and blood NfL samples. Overall, 26/36 studies measured blood NfL using Simoa, 8/36 ECL, 1/36 ELISA and 1 study reported all three assay results. The overall meta-analysis demonstrated that the pooled correlation coefficient estimate for CSF and blood NfL was r=0.72. Heterogeneity was significant: I2=83%, p<0.01. In sensitivity analyses, the pooled correlation coefficient was similar for studies measuring blood NfL using Simoa and ECL (r=0.69 and r=0.68, respectively) but weaker for ELISA (r=0.35).Conclusion Moderate correlations are demonstrated between CSF and blood NfL, especially when blood NfL was measured using Simoa and ECL. Given its high analytical sensitivity, Simoa is the preferred assay for measuring NfL, especially at low or physiological concentrations, and this meta-analysis supports its use as the current most advanced surrogate measure of CSF NfL.PROSPERO registration number CRD42019140469
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