Publications
475 results found
Tipoe T, Fidler S, Frater J, 2022, An exploration of how broadly neutralizing antibodies might induce HIV remission: the 'vaccinal' effect, CURRENT OPINION IN HIV AND AIDS, Vol: 17, Pages: 162-170, ISSN: 1746-630X
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- Citations: 5
Phiri MM, Hensen B, Schaap A, et al., 2022, Adapting community-based sexual and reproductive health services for adolescents and young people aged 15-24 years in response to COVID-19 in Lusaka, Zambia: the implications on the uptake of HIV testing services, BMC Health Services Research, Vol: 22, ISSN: 1472-6963
BackgroundAcross Sub-Saharan Africa, adolescents and young people (AYP) aged 15-24 have limited access to sexual and reproductive health (SRH) services, including HIV testing services (HTS). In response, the Yathu Yathu study was implemented in two high-density communities in Lusaka, Zambia. Yathu Yathu provides comprehensive, community-based, peer-led SRH services, including differentiated HTS (finger-prick and HIV self-testing) and comprehensive sexuality education (CSE). We describe adaptations to the Yathu Yathu intervention in response to the COVID-19 epidemic, and implications on uptake of HTS among AYP.MethodsYathu Yathu provides SRH services through community-based peer-led spaces. AYP in study communities were offered prevention points cards (PPC), which incentivizes and tracks service use. Social media (WhatsApp©/Facebook©) is used to engage and inform AYP about SRH. Due to COVID-19, hubs closed from April-June 2020. We describe adaptations in response to COVID-19 and, using routinely collected PPC data, describe uptake of HTS before (September 2019-March 2020) and after (July-December 2020) adaptations in response to COVID-19. We describe reach of the Yathu Yathu Facebook page and use qualitative data to describe AYP experiences of SRH service access.ResultsDuring hub closures, CSE was delivered via video on social media, resulting in an increase in Facebook page followers from 539(April) to 891(June). WhatsApp groups evolved as a platform to deliver CSE and COVID-19 information, with higher participation among young people aged 20-24. Key service delivery adaptations included: reducing the number of participants in hubs, mandatory handwashing before entry, use of personal protective equipment by staff and provision of facemasks to AYP. HTS were provided as normal. Adaptations led to fewer AYP attending hubs. Uptake of HTS among AYP visiting hubs for the first time after COVID-19-related closures was higher (73.2%) compared to uptake before adap
Reuschl A-K, Mesner D, Shivkumar M, et al., 2022, HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells, CELL REPORTS, Vol: 39, ISSN: 2211-1247
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- Citations: 3
Ogbe A, Pace M, Bittaye M, et al., 2022, Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV, JCI Insight, Vol: 7, Pages: 1-18, ISSN: 2379-3708
Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells > 350 cells/μL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4–6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that, 6 months after vaccination, the majority of measurable immune responses were greater than prevaccination baseline but with evidence of a decline in both humoral and cell-mediated immunity. There was, however, no significant difference compared with a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although they were lower than WT. Preexisting cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater postvaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the ongoing policy to vaccinate PWH against SARS-CoV-2, and they underpin the need for long-term monitoring of responses after vaccination.
Lee MJ, Collins S, Babalis D, et al., 2022, The RIO trial: rationale, design, and the role of community involvement in a randomised placebo-controlled trial of antiretroviral therapy plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) in participants diagnosed with recent HIV infection-study protocol for a two-stage randomised phase II trial, Trials, Vol: 23, ISSN: 1745-6215
Background:Antiretroviral therapy (ART) has led to dramatic improvements in survival for people living with HIV, but is unable to cure infection, or induce viral control off therapy. Designing intervention trials with novel agents with the potential to confer a period of HIV remission without ART remains a key scientific and community goal. We detail the rationale, design, and outcomes of a randomised, placebo-controlled trial of two HIV-specific long-acting broadly neutralising antibodies (bNAbs): 3BNC117-LS and 10-1074-LS, which target CD4 binding site and V3 loop respectively, on post-treatment viral control.Methods:RIO is a randomised, placebo-controlled, double-blinded prospective phase II study. Eligible individuals will have started ART within 3 months of primary HIV infection and have viral sequences that appear to be sensitive to both bNAbs. It will randomise 72 eligible participants 1:1 to the following arms via a two-stage design. In Stage 1, arm A participants are given dual long-acting (LS-variants) bNAbs infusions, followed by intensively monitored Analytical Treatment Interruption (ATI) (n = 36); in arm B, participants receive placebo infusions followed by ATI. The primary endpoint will be time to viral rebound within 36 weeks after ATI. Upon viral rebound, the participant and researcher are unblinded. Participants in arm A recommence ART and complete the study. Participants in arm B are invited to restart ART and enroll into Stage 2 where they will receive open-label LS bNAbs, followed by a second ATI 24 weeks after. Secondary and exploratory endpoints include adverse events, time to undetectable viraemia after restarting ART, immunological markers, HIV proviral DNA, serum bNAb concentrations in blood, bNAb resistance at viral rebound, and quality of life measures.Discussion:The two-stage design was determined in collaboration with community involvement. This design allows all participants the option to receive bNAbs. It also tes
Hall E, Davis K, Ohrnberger J, et al., 2022, Associations between HIV stigma and health-related quality of life among people living with HIV in Zambia and South Africa: Cross-sectional analysis of data from the HPTN071 (PopART) study, AIDS 2022
Henderson M, Georgantaki D, Talajia K, et al., 2022, Inflammatory conditions necessitating immunosuppression in a cohort of young adults with perinatally acquired HIV: a case series, Publisher: WILEY, Pages: 51-52, ISSN: 1464-2662
Henderson M, Elliott T, Crook E, et al., 2022, Cervical screening and HPV testing in young women living with perinatally acquired HIV: an interim assessment of the SHiP study, Publisher: WILEY, Pages: 49-49, ISSN: 1464-2662
Hensen B, Gondwe M, Phiri M, et al., 2022, Access to menstrual hygiene products through incentivised, community-based, peer-led sexual and reproductive health services before and during the COVID-19 pandemic: findings from the Yathu Yathu trial, BMC PUBLIC HEALTH, Vol: 22
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- Citations: 3
Henderson M, Fidler S, Mothe B, et al., 2022, Mitigation strategies to safely conduct HIV treatment research in the context of COVID-19, Journal of the International AIDS Society, Vol: 25, ISSN: 1758-2652
Introduction:The International AIDS Society convened a multidisciplinary committee of experts in December 2020 to provide guidance and key considerations for the safe and ethical management of clinical trials involving people living with HIV (PLWH) during the SARS-CoV-2 pandemic. This consultation did not discuss guidance for the design of prevention studies for people at risk of HIV acquisition, nor for the programmatic delivery of antiretroviral therapy. Discussion:There is strong ambition to continue with HIV research from both PLWH and the research community despite the ongoing SARS-CoV-2 pandemic. How to do this safely and justly remains a critical debate. The SARS-CoV-2 pandemic continues to be highly dynamic. It is expected that with the emergence of effective SARS-CoV-2 prevention and treatment strategies, the risk to PLWH in clinical trials will decline over time. However, with the emergence of more contagious and potentially pathogenic SARS-CoV-2 variants, the effectiveness of current prevention and treatment strategies may be compromised. Uncertainty exists about how equally SARS-CoV-2 prevention and treatment strategies will be available globally, particularly for marginalized populations, many of whom are at high risk of reduced access to ART and/or HIV disease progression. All of these factors must be taken into account when deciding on the feasibility and safety of developing and implementing HIV research.Conclusion:It can be assumed for the foreseeable future that SARS-CoV-2 will persist and continue to pose challenges to conducting clinical research in PLWH. Guidelines regarding how best to implement HIV treatment studies will evolve accordingly. The risks and benefits of performing an HIV clinical trial must be carefully evaluated in the local context on an ongoing basis. With this document, we hope to provide a broad guidance that should remain viable and relevant even as the nature of the pandemic continues to develop.
Wymant C, Bezemer D, Blanquart F, et al., 2022, A highly virulent variant of HIV-1 circulating in the Netherlands, Science, Vol: 375, Pages: 540-545, ISSN: 0036-8075
Changes in viral load and CD4+ T cell decline are expected signals of HIV evolution. By examining data from well-characterized European cohorts, Wymant et al. report an exceptionally virulent subtype of HIV that has been circulating in the Netherlands for several years (see the Perspective by Wertheim). More than one hundred individuals infected with a characteristic subtype B lineage of HIV-1 were found who experienced double the rate of CD4+ cell count declines than expected. By the time they were diagnosed, these individuals were vulnerable to developing AIDS within 2 to 3 years. This virus lineage, which has apparently arisen de novo since around the millennium, shows extensive change across the genome affecting almost 300 amino acids, which makes it hard to discern the mechanism for elevated virulence. —CA
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
Lee MJ, Fidler S, Frater J, 2022, Immunotherapeutic approaches to HIV cure and remission, CURRENT OPINION IN INFECTIOUS DISEASES, Vol: 35, Pages: 31-41, ISSN: 0951-7375
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- Citations: 5
Alagaratnam J, De Francesco D, Zetterberg H, et al., 2022, Correlation between cerebrospinal fluid and plasma neurofilament light protein in treated HIV infection: results from the COBRA study, JOURNAL OF NEUROVIROLOGY, Vol: 28, Pages: 54-63, ISSN: 1355-0284
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- Citations: 7
Limbada M, Bwalya C, Macleod D, et al., 2022, Acceptability and Preferences of Two Different Community Models of ART Delivery in a High Prevalence Urban Setting in Zambia: Cluster-Randomized Trial, Nested in the HPTN 071 (PopART) Study, AIDS AND BEHAVIOR, Vol: 26, Pages: 328-338, ISSN: 1090-7165
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- Citations: 2
Zacharopoulou P, Marchi E, Ogbe A, et al., 2022, Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound, SCIENTIFIC REPORTS, Vol: 12, ISSN: 2045-2322
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- Citations: 5
Hensen B, Phiri M, Schaap A, et al., 2022, Uptake of HIV Testing Services Through Novel Community-Based Sexual and Reproductive Health Services: An Analysis of the Pilot Implementation Phase of the Yathu Yathu Intervention for Adolescents and Young People Aged 15-24 in Lusaka, Zambia, AIDS AND BEHAVIOR, Vol: 26, Pages: 172-182, ISSN: 1090-7165
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- Citations: 3
Phiri MM, Schaap A, Simwinga M, et al., 2022, Closing the gap: did delivery approaches complementary to home-based testing reach men with HIV testing services during and after the HPTN 071 (PopART) trial in Zambia?, JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, Vol: 25
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- Citations: 3
Phetsouphanh C, Phalora P, Hackstein C-P, et al., 2021, Human MAIT cells respond to and suppress HIV-1, ELIFE, Vol: 10, ISSN: 2050-084X
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- Citations: 10
Grant-McAuley W, Klock E, Laeyendecker O, et al., 2021, Evaluation of multi-assay algorithms for identifying individuals with recent HIV infection: HPTN 071 (PopART), PLOS ONE, Vol: 16, ISSN: 1932-6203
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- Citations: 4
Simpson N, Kydd A, Phiri M, et al., 2021, Insaka: mobile phone support groups for adolescent pregnant women living with HIV (vol 21, 663, 2021), BMC PREGNANCY AND CHILDBIRTH, Vol: 21
Deeks SG, Archin N, Cannon P, et al., 2021, Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021, NATURE MEDICINE, Vol: 27, Pages: 2085-2098, ISSN: 1078-8956
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- Citations: 93
Klock E, Wilson E, Fernandez RE, et al., 2021, Validation of population-level HIV-1 incidence estimation by cross-sectional incidence assays in the HPTN 071 (PopART) trial, JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, Vol: 24
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- Citations: 7
Limbada M, Macleod D, Situmbeko V, et al., 2021, Rates of viral suppression in a cohort of people with stable HIV from two community models of ART delivery versus facility-based HIV care in Lusaka, Zambia: a cluster-randomised, non-inferiority trial nested in the HPTN 071 (PopART) trial, The Lancet HIV, Vol: 9, Pages: E13-E23, ISSN: 2405-4704
BackgroundNon-facility-based antiretroviral therapy (ART) delivery for people with stable HIV might increase sustainable ART coverage in low-income and middle-income countries. Within the HPTN 071 (PopART) trial, two interventions, home-based delivery (HBD) and adherence clubs (AC), which included groups of 15–30 participants who met at a communal venue, were compared with standard of care (SoC). In this trial we looked at the effectiveness and feasibility of these alternative models of care. Specifically, this trial aimed to assess whether these models of care had similar virological suppression to that of SoC 12 months after enrolment.MethodsThis was a three-arm, cluster-randomised, non-inferiority trial, done in two urban communities in Lusaka, Zambia included in the HPTN 071 trial. The two communities were split into zones, which were randomly assigned (1:1:1) to the three treatment strategies: 35 zones to the SoC group, 35 zones to the HBD group, and 34 zones to the AC group. ART and adherence support were delivered once every 3 months at home for the HBD group, in groups of 15–30 people in the AC group, or in the clinic for the SoC group. Adults with HIV who were receiving first-line ART for at least 6 months, virally suppressed using national HIV guidelines in the last 12 months, had no other health conditions requiring the clinicians attention, live in the study catchment area, and provided written informed consent, were eligible for inclusion. The primary endpoint was viral suppression at 12 months (with a 6 month final measurement window [ie, 9–15 months]), defined as less than 1000 HIV RNA copies per mL, with a non-inferiority margin of 5%.FindingsBetween May 5 and Dec 19, 2017, 9900 individuals were screened for inclusion, of whom 2489 (25·1%) participants were enrolled into the trial: 781 (31%) in the SoC group, 852 (34%) in the HBD group, and 856 (34%) in the AC group. A higher proportion of participants had viral load measurem
Bell-Mandla NF, Sloot R, Maarman G, et al., 2021, Improving retention of community-recruited participants in HIV prevention research through Saturday household visits; findings from the HPTN 071 (PopART) study in South Africa, BMC MEDICAL RESEARCH METHODOLOGY, Vol: 21
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- Citations: 2
Granger LA, Huettner I, Debeljak F, et al., 2021, Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort, AIDS, Vol: 35, Pages: 2073-2084, ISSN: 0269-9370
Objective: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts.Design and methods: Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time.Results: In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3–4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes.Conclusion: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.
Hensen B, Phiri M, Schaap A, et al., 2021, Yathu Yathu ("For us, by us"): Design of a cluster-randomised trial of the impact of community-based, peer-led comprehensive sexual and reproductive health services for adolescents and young people aged 15 to 24 in Lusaka, Zambia, CONTEMPORARY CLINICAL TRIALS, Vol: 110, ISSN: 1551-7144
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- Citations: 4
Simpson N, Kydd A, Phiri M, et al., 2021, Insaka: mobile phone support groups for adolescent pregnant women living with HIV, BMC PREGNANCY AND CHILDBIRTH, Vol: 21
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- Citations: 5
Lee MJ, Snell LB, Douthwaite ST, et al., 2021, Clinical outcomes of patients with and without HIV hospitalized with COVID-19 in England during the early stages of the pandemic: a matched retrospective multi-centre analysis (RECEDE-C19 study), HIV Medicine, Vol: 23, Pages: 121-133, ISSN: 1464-2662
BackgroundThe contribution of HIV to COVID-19 outcomes in hospitalized inpatients remains unclear. We conducted a multi-centre, retrospective matched cohort study of SARS-CoV-2 PCR-positive hospital inpatients analysed by HIV status.MethodsHIV-negative patients were matched to people living with HIV (PLWH) admitted from 1 February 2020 to 31 May 2020 up to a 3:1 ratio by the following: hospital site, SARS-CoV-2 test date ± 7 days, age ± 5 years, gender, and index of multiple deprivation decile ± 1. The primary objective was clinical improvement (two-point improvement or better on a seven-point ordinal scale) or hospital discharge by day 28, whichever was earlier.ResultsA total of 68 PLWH and 181 HIV-negative comparators were included. In unadjusted analyses, PLWH had a reduced hazard of achieving clinical improvement or discharge [adjusted hazard ratio (aHR) = 0.57, 95% confidence interval (CI): 0.39–0.85, p = 0.005], but this association was ameliorated (aHR = 0.70, 95% CI: 0.43–1.17, p = 0.18) after additional adjustment for ethnicity, frailty, baseline hypoxaemia, duration of symptoms prior to baseline, body mass index (BMI) categories and comorbidities. Baseline frailty (aHR = 0.79, 95% CI: 0.65–0.95, p = 0.011), malignancy (aHR = 0.37, 95% CI 0.17, 0.82, p = 0.014) remained associated with poorer outcomes. The PLWH were more likely to be of black, Asian and minority ethnic background (75.0% vs 48.6%, p = 0.0002), higher median clinical frailty score [3 × interquartile range (IQR): 2–5 vs, 2 × IQR: 1–4, p = 0.0069), and to have a non-significantly higher proportion of active malignancy (14.4% vs 9.9%, p = 0.29).ConclusionsAdjusting for confounding comorbidities and demographics in a matched cohort ameliorated differences in outcomes of PLWH hospitalized with COVID-19, highlighting the importance of an appropriate comparison group when assessing outcomes of PLWH hospitalized with COVID-19.
Pickles M, Cori A, Probert WJM, et al., 2021, PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial, PLOS COMPUTATIONAL BIOLOGY, Vol: 17, ISSN: 1553-734X
Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention.
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