ABSTRACT
Background: To test efficacy, HIV cure-related trials often require a period of intensively monitored interruption of antiretroviral therapy (ART) (analytical treatment interruption or ATI). As individuals who started ART during primary HIV-1 infection (PHI) are often recruited, we have asked people already enrolled into an observational PHI study about their willingness and concerns around participating in cure-related studies involving ATIs. Methods: People who were diagnosed with PHI and started ART, attending two London HIV clinics, provided informed consent to complete a digital survey in clinic between 21/07/21 to October 31, 2023. Questions comprised sociodemographics, motivations, concerns and practical considerations influencing willingness to participate in studies involving ATIs. Hierarchical clustering of responses was performed using the 'pheatmap' R statistical package and ranked from most to least concerned. Responses were cross-referenced with enrolment into an ATI study which recruited from this cohort. Results: Of 352 eligible participants, 75 completed the survey. The majority were white, cisgender men who have sex with men, 34/75 (45 %) were born outside the UK. 29 (39 %) expressed interest in joining ATI studies. Participants who were interested or unsure in joining ATI studies were primarily motivated (53/65, 82 % very or moderately interested) by an altruistic desire to help scientific research. Across all participants, onward HIV transmission was the predominant concern (67/75, 89 % very or moderately concerned), and similar levels of concerns reported if the HIV-1 viral load threshold to restarting ART was increased from 500 to 50 000 copies/mL. Most participants preferred weekly (23/65, 35 %) or fortnightly (11/65, 17 %) viral load monitoring during an ATI. Before taking part in a study involving an ATI, participants stated they would prefer to discuss this with their HIV doctor (55/65, 85 %). Conclusion: In this small survey, 39 % of respondents expressed interest in joining studies involving ATIs, primarily for altruistic reasons. Participants were more interested in joining a potential ATI study if a novel intervention was included than simply an ATI alone. The main concern expressed was risk of viral transmission. To inform practical and study design considerations for future ATI studies, unrestricted access for mitigation of transmission risk should be included, and regular, frequent viral load monitoring is preferred.
ABSTRACT
COVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT162b2 at a short (3-4 week) or extended interval (8-12 weeks) and following a third vaccination approximately 6-8 months later. We show that whilst an extended interval between the first two vaccinations can greatly increase the breadth of the immune response and generate a higher proportion of Spike reactive memory B cells, a third vaccination leads to similar levels between the two groups. Furthermore, we show that the third vaccine dose enhances neutralization activity against omicron lineage members BA.1, BA.2 and BA.4/BA.5 and this is further increased following breakthrough infection during the UK omicron wave. These findings are relevant for vaccination strategies in populations where COVID-19 vaccine coverage remains low.
