Imperial College London

Professor Sarah Fidler BSc. MBBS. FRCP. PhD

Faculty of MedicineDepartment of Infectious Disease

Professor of HIV and Communicable Diseases
 
 
 
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Contact

 

+44 (0)20 7594 6230s.fidler

 
 
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Location

 

clinical trial centre Winston Churchill wingMedical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

478 results found

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

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

Journal article

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

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

Journal article

Horvath A, Rogers L, Pollakis G, Baranov O, Pieroth N, Joseph S, Chachage M, Heitzer A, Maganga L, Msafiri F, Joachim A, Viegas E, Eller L-A, Kibuuka H, Rerks-Ngarm S, Pitisuttithum P, Nitayapan S, Dhitavat J, Premsri N, Fidler S, Shattock RJJ, Robb ML, Weber J, McCormack S, Munseri PJ, Lyamuya E, Nilsson C, Kroidl A, Hoelscher M, Wagner R, Geldmacher C, Held Ket al., 2023, Systematic comparison of HIV-1 Envelope-specific IgG responses induced by different vaccination regimens: Can we steer IgG recognition towards regions of viral vulnerability?, Frontiers in Immunology, Vol: 13, Pages: 1-16, ISSN: 1664-3224

Immunogens and vaccination regimens can influence patterns of immune-epitope recognition, steering them towards or away from epitopes of potential viral vulnerability. HIV-1 envelope (Env)-specific antibodies targeting variable region 2 (V2) or 3 (V3) correlated with protection during the RV144 trial, however, it was suggested that the immunodominant V3 region might divert antibody responses away from other relevant sites. We mapped IgG responses against linear Env epitopes in five clinical HIV vaccine trials, revealing a specific pattern of Env targeting for each regimen. Notable V2 responses were only induced in trials administering CRF01_AE based immunogens, but targeting of V3 was seen in all trials, with the soluble, trimeric CN54gp140 protein eliciting robust V3 recognition. Strong V3 targeting was linked to greater overall response, increased number of total recognised antigenic regions, and where present, stronger V2 recognition. Hence, strong induction of V3-specific antibodies did not negatively impact the targeting of other linear epitopes in this study, suggesting that the induction of antibodies against V3 and other regions of potential viral vulnerability need not be necessarily mutually exclusive.

Journal article

Shanaube K, Schaap A, Mureithi L, Amofa-Sekyi M, Paulsen R, Cheeba M, Kangololo B, Vermaak R, Sisam C, Kosloff B, de Haas P, Fidler S, Ruperez M, Hayes R, Floyd S, Ayles H, TREATS Study Teamet al., 2023, The impact of a combined TB/HIV intervention on the incidence of TB infection among adolescents and young adults in the HPTN 071 (PopART) trial communities in Zambia and South Africa., PLOS Glob Public Health, Vol: 3

BACKGROUND: HPTN071 (PopART) was a cluster randomized trial conducted in Zambian and South African (SA) communities, between 2013-2018. The PopART intervention (universal HIV-testing and treatment (UTT) combined with population-level TB symptom screening) was implemented in 14 communities. The TREATS study (2017-2021) was conducted to evaluate the impact of the PopART intervention on TB outcomes. We report on the impact of the combined TB/HIV intervention on the incidence of TB infection in a cohort of adolescents and young adults (AYA) aged 15-24 years. METHODS: A random sample of AYA was enrolled between July 2018 and July 2019 in 7 intervention vs 7 standard-of-care communities. We collected questionnaire data on risk factors for TB, and blood for measuring TB infection using QuantiFERON (QFT) Plus. AYA were seen at months 12 and 24 with all procedures repeated. Primary outcome was incidence of TB infection comparing intervention and standard-of-care communities. An incident case was defined as a participant with QFT interferon-gamma response of < 0.2 IU/ml plasma ('negative') at baseline and a QFT interferon-gamma response of > = 0.7 IU/ml ('positive') at follow up. RESULTS: We enrolled 4,648 AYA, 2,223 (47.8%) had a negative QFT-plus result at baseline, 1,902 (85.6%) had a follow up blood sample taken at 12 months or 24 months. Among the 1,902 AYA, followed for 2,987 person-years, 213 had incident TB infection giving (7.1 per 100 person-years). TB infection incidence rates were 8.7 per 100 person-years in intervention communities compared to 6.0 per 100 person-years in standard-of-care communities. There was no evidence the intervention reduced the transmission of TB (incidence-rate-ratio of 1.45, 95%CI 0.97-2.15, p = 0.063). CONCLUSION: In our trial setting, we found no evidence that UTT combined with TB active case finding reduced the incidence of TB infection at population level. Our data will inform future modelling work to better understand the popul

Journal article

Phiri MM, Hensen B, Sigande LM, Floyd S, Schaap AJ, Simuyaba M, Mwenge L, Zulu-Phiri R, Mwape L, Fidler S, Simwinga M, Hayes R, Ayles HMet al., 2023, Factors associated with use of community-based, peer-led sexual and reproductive health services by adolescent boys and young men aged 18-24 in Lusaka, Zambia: A case control study nested in the Yathu Yathu trial., PLOS Glob Public Health, Vol: 3

INTRODUCTION: Adolescents and young people (AYP) aged 15-24 years have the least access to facility-based sexual and reproductive health (SRH) services, including HIV services. The Yathu-Yathu cluster-randomized trial (CRT) in Zambia tested whether a novel peer-led community-based approach increased knowledge of HIV status amongst AYP. In this nested case-control study, we aimed to identify factors associated with non-attendance to the Yathu Yathu hubs by adolescent boys and young men (ABYM) aged 18-24-years. METHODS: Yathu Yathu was a CRT conducted in two communities in Lusaka, Zambia, with 10 intervention and 10 control zones. AYP in all zones were offered prevention points cards (PPC), which incentivized and tracked service use at the hubs and health facility. In intervention zones, services were provided to AYP through community-based spaces (hubs) led by peer support workers. In these zones, cases were defined as those not having accessed any service at a hub and controls as those that accessed at least one service. Data were collected from October 2020 to January 2021 and analysed using methods appropriate for unmatched case-control studies. RESULTS: 161 cases and 160 controls consented to participate in the study. Participants aged 20-24 years (adjOR 1.99, 95%CI 1.26-3.12, p = 0.003), who were educated up to college level (adjOR 8.47,95%CI 2.08-34.53, p = 0.001) or who reported being employed in the last 12 months (adjOR 2.15, 95%CI 1.31-3.53, p = 0.002) were more likely to not attend the hubs. ABYM who had a friend with a PPC were more likely to attend the hubs (adjOR 0.18 95%CI 0.09-0.35, p<0.001). Most cases reported having their last HIV test at the local government health facility (58%) while most controls reported HIV-testing at a Yathu Yathu hub (82%). Among the controls, 84% (134/160) rated the hub experience as excellent. Among cases, 65% (104/161) stated they didn't visit the hubs "due to employment". CONCLUSIONS: Despite Yathu Yathu se

Journal article

Amofa-Sekyi M, Schaap A, Mureithi L, Kosloff B, Cheeba M, Kangololo B, Vermaak R, Paulsen R, Ruperez M, Floyd S, de Haas P, Fidler S, Hayes R, Ayles H, Shanaube K, TREATS study teamet al., 2023, Prevalence and risk factors of M tuberculosis infection in young people across 14 communities in Zambia and South Africa., PLOS Glob Public Health, Vol: 3

BACKGROUND: From 2018-2021 the TB Reduction through Expanded Antiretroviral Treatment and TB Screening (TREATS) project took place in 21 Zambian and South African communities. The TREATS Incidence of TB Infection Cohort Study was conducted in adolescents and young people (AYP), aged 15-24 years in 14 communities. We describe the baseline prevalence and risk factors of Mycobacterium tuberculosis (M. tuberculosis) infection among this cohort and explore the quantitative QFT-Plus interferon gamma (IFN-γ) responses. METHODS AND FINDINGS: A random sample of approximately 300 AYP per community were recruited and information on TB/HIV risk factors, TB symptoms and social mixing patterns collected. QuantiFERON TB Gold Plus assay (QFT-Plus) was used to detect M. tuberculosis infection, following manufacturer's instructions. Logistic regression was used to determine factors associated with infection. 5577 eligible AYP were invited to participate across both countries, with 4648 enrolled. QFT-Plus results were available for 4529: 2552(Zambia) and 1977(South Africa). Overall, 47.6% (2156/4529) AYP had positive QFT-Plus results, the prevalence of infection in South Africa being twice that in Zambia (64.7% (1280/1977) vs 34.3% (867/2552) p<0.001). Infection was associated with age, household contact with TB and alcohol in Zambia but showed no associations in South Africa. The antigen tube differential (TB2-TB1>0.6 IU/ml) of the assay at baseline showed no evidence of association with recent TB exposure. CONCLUSION: The high prevalence of infection in AYP warrants urgent action to address TB control, especially in South Africa. Further research is required to delineate antigen tube responses of the QFT-Plus assay more precisely to fully realise the benefit of the additional TB2 tube in high TB/HIV burden settings.

Journal article

Sabapathy K, Balzer L, Larmarange J, Block L, Floyd S, Iwuji C, Wirth K, Ayles H, Fidler S, Kamya M, Petersen M, Havlir D, Dabis F, Moore J, Hayes Ret al., 2022, Achieving the UNAIDS 90-90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa, BMC PUBLIC HEALTH, Vol: 22

Journal article

Abdool Karim Q, Archary D, Barré-Sinoussi F, Broliden K, Cabrera C, Chiodi F, Fidler S, Gengiah T, Herrera C, KHARSANY A, Liebenberg L, Mahomed S, Menu E, Moog C, Scarlatti G, Seddiki N, Sivro A, Cavarelli Met al., 2022, Women for science and science for women: Gaps, challenges and opportunities towards optimizing pre-exposure prophylaxis for HIV-1 prevention, Frontiers in Immunology, Vol: 13, Pages: 1-21, ISSN: 1664-3224

Preventing new HIV infections remains a global challenge. Young women continue to bear a disproportionate burden of infection. Oral pre-exposure prophylaxis (PrEP), offers a novel women-initiated prevention technology and PrEP trials completed to date underscore the importance of their inclusion early in trials evaluating new HIV PrEP technologies. Data from completed topical and systemic PrEP trials highlight the role of gender specific physiological and social factors that impact PrEP uptake, adherence and efficacy. Here we review the past and current developments of HIV-1 prevention options for women with special focus on PrEP considering the diverse factors that can impact PrEP efficacy. Furthermore, we highlight the importance of inclusion of female scientists, clinicians, and community advocates in scientific efforts to further improve HIV prevention strategies.

Journal article

Shanaube K, Gachie T, Hoddinott G, Schaap A, Floyd S, Mainga T, Bond V, Hayes R, Fidler S, Ayles H, HPTN071 PopART Study Teamet al., 2022, Depressive symptoms and HIV risk behaviours among adolescents enrolled in the HPTN071 (PopART) trial in Zambia and South Africa, PLoS One, Vol: 17, ISSN: 1932-6203

BACKGROUND: Mental health is a critical and neglected public health problem for adolescents in sub-Saharan Africa. In this paper we aim to determine the prevalence of depressive symptoms and the association with HIV risk behaviours in adolescents aged 15-19 years in Zambia and SA. METHODS: We conducted a cross-sectional survey from August-November 2017 in seven control communities of HPTN 071 (PopART) trial (a community-randomised trial of universal HIV testing and treatment), enrolling approximately 1400 eligible adolescents. HIV-status was self-reported. Depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ), with a positive screen if adolescents scored ≥12. We fitted a logistic regression model to identify correlates of depressive symptoms with subgroup analyses among those who self-reported ever having had sex, by gender and country. RESULTS: Out of 6997 households approached, 6057 (86.6%) were enumerated. 2546 adolescents were enumerated of whom 2120 (83.3%) consented to participate and were administered the SMFQ. The prevalence of depressive symptoms was 584/2120 (27.6%) [95%CI: 25.7%-29.5%]. Adolescents in SA were less likely to experience depressive symptoms (Adjusted Odds Ratio [AOR] = 0.63 (95% CI: 0.50, 0.79), p-value<0.0001). Female adolescents (AOR = 1.46 (95% CI: 1.19, 1.81), p-value<0.0001); those who reported ever having sex and being forced into sex (AOR = 1.80 (95% CI: 1.45, 2.23), p-value<0.001) and AOR = 1.67 (95% CI: 0.99, 2.84); p-value = 0.057 respectively) were more likely to experience depressive symptoms. Among 850 (40.1%) adolescents who self-reported to ever having had sex; those who used alcohol/drugs during their last sexual encounter were more likely to experience depressive symptoms (AOR = 2.18 (95% CI: 1.37, 3.47); p-value = 0.001), whereas those who reported using a condom were less likely to experience depressive symptoms (AOR = 0.74 (95% CI: 0.55, 1.00); p-value = 0.053). CONCLUSION: Th

Journal article

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

Journal article

Cook L, O'dell G, Vourvou E, Palanicawandar R, Marks S, Milojkovic D, Apperley J, Loaiza S, Claudiani S, Bua M, Hockings C, Macdonald D, Chaidos A, Pavlu J, Cooper N, Fidler S, Randell P, Innes Aet al., 2022, Third primary SARS-CoV-2 mRNA vaccines enhance antibody responses in most patients with haematological malignancies, Nature Communications, Vol: 13, Pages: 1-6, ISSN: 2041-1723

SARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have reduced hospitalisations and deaths, but vaccine efficacy in patients with haematological malignancies is known to be reduced. The UK-strategyoffered a third, mRNA-based, vaccine as an extension to the primary course in these patients. The MARCH database is a retrospective observational study of serological responses in patients with blood disorders. Here we present data on 381 patients with haematological malignancies. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued sub-optimal vaccine responses who may benefit from additional doses, prophylactic extended half-life neutralising monoclonal therapies (nMAB) or prompt nMAB treatment in the event of SARS-CoV-2 infection.

Journal article

Fogel JM, Zewdie K, Clarke WA, Piwowar-Manning E, Breaud A, Moore A, Kosloff B, Shanaube K, van Zyl G, Scheepers M, Floyd S, Bock P, Ayles H, Fidler S, Hayes R, Donnell D, Eshleman SHet al., 2022, Antiretroviral Drug Detection in a Community-Randomized Trial of Universal HIV Testing and Treatment: HPTN 071 (PopART), OPEN FORUM INFECTIOUS DISEASES, Vol: 9, ISSN: 2328-8957

Journal article

Wilson E, Donnell D, Skalland T, Floyd S, Moore A, Bell-Mandla N, Bwalya J, Kasese N, Dunbar R, Shanaube K, Kosloff B, Laeyendecker O, Agyei Y, Hoddinott G, Bock P, Fidler S, Hayes R, Ayles H, HPTN 071 PopART Study Teamet al., 2022, Impact of universal testing and treatment on sexual risk behaviour and herpes simplex virus type 2: a prespecified secondary outcomes analysis of the HPTN 071 (PopART) community-randomised trial., Lancet HIV, Vol: 9, Pages: e760-e770

BACKGROUND: Comprehensive HIV prevention strategies have raised concerns that knowledge of interventions to reduce risk of HIV infection might mitigate an individual's perception of risk, resulting in riskier sexual behaviour. We investigated the prespecified secondary outcomes of the HPTN 071 (PopART) trial to determine whether a combination HIV prevention strategy, including universal HIV testing and treatment, changed sexual behaviour; specifically, we investigated whether there was evidence of sexual risk compensation. METHODS: HPTN 071 (PopART) was a cluster-randomised trial conducted during 2013-18, in which we randomly assigned 21 communities with high HIV prevalence in Zambia and South Africa (total population, approximately 1 million) to combination prevention intervention with universal antiretroviral therapy (ART; arm A), prevention intervention with ART provided according to local guidelines (universal since 2016; arm B), or standard of care (arm C). The trial included a population cohort of approximately 2000 randomly selected adults (aged 18-44 years) in each community (N=38 474 at baseline) who were followed up for 36 months. A prespecified secondary objective was to evaluate the impact of the PopART intervention compared with standard of care on herpes simplex virus type 2 (HSV-2) and sexual behaviour (N=20 422 completed final visit). Secondary endpoints included differences in sexual risk behaviour measures at 36 months and were assessed using a two-stage method for matched cluster-randomised trials. This trial is registered with ClinicalTrials. gov, number NCT01900977. FINDINGS: The PopART intervention did not substantially change probability of self-reported multiple sex partners, sexual debut, or pregnancy in women at 36 months. Adjusted for baseline community prevalence, reported condomless sex was significantly lower in arm A versus arm C (adjusted prevalence ratio 0·80 [95% CI 0·64-0·99]; p=0·04) but not in arm B ve

Journal article

Hayes R, Ayles H, Fidler S, 2022, Lessons from the HPTN 071 (PopART) trial., Lancet HIV, Vol: 9, Pages: e736-e737

Journal article

Simwinga M, Ndubani R, Schaap A, Ziba D, Bwalya C, Belemu S, Ngwenya F, Bwalya J, Shanaube K, Hoddinott G, White R, Bock P, Fidler S, Hayes R, Seeley J, Ayles H, Bond V, HPTN 071 PopART Study Teamet al., 2022, Disseminating complex primary outcome results from a community-randomised trial to Zambian communities: lessons learned using a community dialogue approach in the HPTN 071 (PopART) trial., Lancet HIV, Vol: 9, Pages: e801-e808

The HPTN 071 (PopART) trial of universal HIV testing and treatment to reduce HIV incidence was conducted in nine communities in South Africa and 12 in Zambia. The trial's primary outcome results were complicated to explain. Dissemination of these complicated results in participating communities in Zambia was done using a community dialogue approach. The approach, which involved interactive activities and a gradual and systematic approach to discussion of results in each community, facilitated respect and inclusion of participants in the dissemination process. The use of local language, pictures, images, and familiar analogies enhanced comprehension of the findings and created a two-way communication process between researchers and participants. The dialogue approach enabled both groups to use community perspectives, lived experiences, and local socio-structural features to interpret the trial results. Further, community members reflected on what the results meant to them individually and collectively. Although this community dialogue was both productive and appreciated, making this community interpretation apparent across disciplines in key quantitative scientific outputs remained a challenge.

Journal article

Macleod D, Shanaube K, Skalland T, Limbada M, Mandla N, Bwalya J, Schaap A, Yang B, Donnell D, Piwowar-Manning E, Eshleman SH, Hoddinott G, Bond V, Moore A, Griffith S, Bock P, Ayles H, Fidler S, Hayes R, Floyd S, HPTN 071 PopART Study Teamet al., 2022, Viral suppression and self-reported ART adherence after 3 years of universal testing and treatment in the HPTN 071 (PopART) community-randomised trial in Zambia and South Africa: a cross-sectional analysis., Lancet HIV, Vol: 9, Pages: e751-e759

BACKGROUND: In 2014, UNAIDS set the target that 90% of individuals on antiretroviral therapy (ART) be virally suppressed. Here, we use data from the HPTN 071 (PopART) trial to report whether the introduction of universal testing and treatment has affected viral suppression or treatment adherence among individuals who self-reported they were taking ART, and identify risk factors for these outcomes. METHODS: This was a cross-sectional study nested within the randomly selected population cohort of the PopART trial. The trial took place in 21 communities in Zambia and South Africa. Analyses included 3570 HIV-positive participants who were seen at the second follow-up visit in 2016-17 and who self-reported that they were currently taking ART. Viral suppression was defined as HIV RNA of less than 400 copies per mL from a blood sample collected during the cohort visit, and ART adherence was measured using self-reporting (reported as no missed pills in last 7 days). Prevalences of these outcomes were compared across three trial arms using a two-stage approach suitable for clustered data. Each arm consisted of seven communities, with one arm receiving a combination HIV prevention package including immediate ART initiation, one receiving a combination HIV prevention package excluding immediate ART initiation and one arm receving standard of care. Risk factors for each of the outcomes were assessed using logistic regression. FINDINGS: Among the 3570 participants who self-reported that they were currently on ART, 416 (11·7%) of 3554 were not virally suppressed (16 were missing viral suppression status) and 345 (9·7%) of 3566 reported being non-adherent to ART (four were missing adherence status). The proportion not virally suppressed was higher in communities in South Africa (195 [16·4%] of 1191) than in Zambia (221 [9·4%] of 2363). There was no evidence that the prevalence of the outcomes differed between trial arms. There was evidence that men, you

Journal article

Gunst JD, Pahus MH, Rosas-Umbert M, Lu I-N, Benfield T, Nielsen H, Johansen IS, Mohey R, Ostergaard L, Klastrup V, Khan M, Schleimann MH, Olesen R, Stovring H, Denton PW, Kinloch NN, Copertino DC, Ward AR, Alberto WDC, Nielsen SD, Puertas MC, Ramos V, Reeves JD, Petropoulos CJ, Martinez-Picado J, Brumme ZL, Jones RB, Fox J, Tolstrup M, Nussenzweig MC, Caskey M, Fidler S, Sogaard OSet al., 2022, Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial, NATURE MEDICINE, Vol: 28, Pages: 2424-+, ISSN: 1078-8956

Journal article

Probert WJM, Sauter R, Pickles M, Cori A, Bell-Mandla NF, Bwalya J, Abeler-Dörner L, Bock P, Donnell DJ, Floyd S, Macleod D, Piwowar-Manning E, Skalland T, Shanaube K, Wilson E, Yang B, Ayles H, Fidler S, Hayes RJ, Fraser C, Hayes R, Fidler S, Beyers N, Ayles H, Bock P, El-Sadr W, Cohen M, Eshleman S, Agyei Y, Piwowar-Manning E, Bond V, Hoddinott G, Donnell D, Floyd S, Wilson E, Emel L, Noble H, Macleod D, Burns D, Fraser C, Cori A, Sista N, Griffith S, Moore A, Headen T, White R, Miller E, Hargreaves J, Hauck K, Thomas R, Limbada M, Bwalya J, Pickles M, Sabapathy K, Schaap A, Dunbar R, Shanaube K, Yang B, Simwinga M, Smith P, Vermund S, Mandla N, Makola N, van Deventer A, James A, Jennings K, Kruger J, Phiri M, Kosloff B, Mwenge L, Kanema S, Sauter R, Probert W, Kumar R, Sakala E, Silumesi A, Skalland T, Yuhas Ket al., 2022, Projected outcomes of universal testing and treatment in a generalised HIV epidemic in Zambia and South Africa (the HPTN 071 [PopART] trial): a modelling study, The Lancet HIV, Vol: 9, Pages: e771-e780, ISSN: 2352-3018

BackgroundThe long-term impact of universal home-based testing and treatment as part of universal testing and treatment (UTT) on HIV incidence is unknown. We made projections using a detailed individual-based model of the effect of the intervention delivered in the HPTN 071 (PopART) cluster-randomised trial.MethodsIn this modelling study, we fitted an individual-based model to the HIV epidemic and HIV care cascade in 21 high prevalence communities in Zambia and South Africa that were part of the PopART cluster-randomised trial (intervention period Nov 1, 2013, to Dec 31, 2017). The model represents coverage of home-based testing and counselling by age and sex, delivered as part of the trial, antiretroviral therapy (ART) uptake, and any changes in national guidelines on ART eligibility. In PopART, communities were randomly assigned to one of three arms: arm A received the full PopART intervention for all individuals who tested positive for HIV, arm B received the intervention with ART provided in accordance with national guidelines, and arm C received standard of care. We fitted the model to trial data twice using Approximate Bayesian Computation, once before data unblinding and then again after data unblinding. We compared projections of intervention impact with observed effects, and for four different scenarios of UTT up to Jan 1, 2030 in the study communities.FindingsCompared with standard of care, a 51% (95% credible interval 40–60) reduction in HIV incidence is projected if the trial intervention (arms A and B combined) is continued from 2020 to 2030, over and above a declining trend in HIV incidence under standard of care.InterpretationA widespread and continued commitment to UTT via home-based testing and counselling can have a substantial effect on HIV incidence in high prevalence communities.FundingNational Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill &

Journal article

Rosas-Umbert M, Gunst JD, Pahus MH, Olesen R, Schleimann M, Denton PW, Ramos V, Ward A, Kinloch NN, Copertino DC, Escriba T, Llano A, Brumme ZL, Jones RB, Mothe B, Brander C, Fox J, Nussenzweig MC, Fidler S, Caskey M, Tolstrup M, Sogaard OSet al., 2022, Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8<SUP>+</SUP> T cell immunity, NATURE COMMUNICATIONS, Vol: 13

Journal article

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

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

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Mallik I, Pasvol T, Frize G, Ayres S, Barrera A, Fidler S, Foster Cet al., 2022, Psychotic disorders in young adults with perinatally acquired HIV: a UK case series, PSYCHOLOGICAL MEDICINE, Vol: 52, Pages: 2263-2269, ISSN: 0033-2917

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Pace M, Ogbe A, Hurst J, Robinson N, Meyerowitz J, Olejniczak N, Thornhill JP, Jones M, Waters A, Lwanga J, Kuldanek K, Hall R, Zacharopoulou P, Martin GE, Brown H, Nwokolo N, Peppa D, Fox J, Fidler S, Frater Jet al., 2022, Impact of antiretroviral therapy in primary HIV infection on natural killer cell function and the association with viral rebound and HIV DNA following treatment interruption, FRONTIERS IN IMMUNOLOGY, Vol: 13, ISSN: 1664-3224

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Hazell GA, Nott VR, Ayres S, Frize G, Kirkhope N, Fidler S, Foster Cet al., 2022, Impact of SARS-CoV-2 pandemic on viral suppression for young adults living with perinatally acquired HIV infection, AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV, ISSN: 0954-0121

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Davis K, Pickles M, Gregson S, Hargreaves J, Ayles H, Bock P, Pliakas T, Thomas R, Ohrnberger J, Bwalya J, Bell-Mandla N, Shanaube K, Probert W, Hoddinott G, Bond V, Hayes R, Fidler S, Hauck Ket al., 2022, The effect of universal testing and treatment for HIV on health-related quality of life - data from the HPTN 071 (PopART) cluster randomised trial in Zambia and South Africa, AIDS 2022, Publisher: International AIDS Society, ISSN: 1758-2652

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Chaudron SE, Zhao L, Macinthyre-Crockett G, Thompson L, Baudi I, Limbada M, Floyd S, Kosloff B, Shanaube K, Fidler S, Hayes R, Ayles H, Herbeck J, Fraser C, Bonsall Det al., 2022, A rapid, integrated method to monitor HIV viral load, drug resistance, and transmission patterns from finger-prick blood samples, Publisher: JOHN WILEY & SONS LTD, Pages: 19-20

Conference paper

Hargreaves JR, Pliakas T, Hoddinott G, Mainga T, Mubekapi-Musadaidzwa C, Donnell D, Wilson E, Piwowar-Manning E, Agyei Y, Bell-Mandla NF, Dunbar R, Schaap A, Macleod D, Floyd S, Bock P, Fidler S, Seeley J, Stangl A, Bond V, Ayles H, Hayes RJet al., 2022, The association between HIV stigma and HIV incidence in the context of universal testing and treatment: analysis of data from the HPTN 071 (PopART) trial in Zambia and South Africa, JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, Vol: 25

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Fogel JM, Wilson EA, Piwowar-Manning E, Breaud A, Clarke W, Petropoulos C, Moore A, Fraser C, Kosloff B, Shanaube K, van Zyl G, Scheepers M, Floyd S, Bock P, Ayles H, Fidler S, Hayes R, Donnell D, Eshleman SHet al., 2022, HIV drug resistance in a community-randomized trial of universal testing and treatment: HPTN 071 (PopART), JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, Vol: 25

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Floyd S, Klinkenberg E, de Haas P, Kosloff B, Gachie T, Dodd PJ, Ruperez M, Wapamesa C, Burnett MJ, Kalisvaart N, Vermaak R, Mainga T, Schaap A, Fidler S, Mureithi L, Shanaube K, Hayes R, Ayles Het al., 2022, Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa, BMJ OPEN, Vol: 12, ISSN: 2044-6055

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