Showing papers by "Chloe Orkin published in 2023"

Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir + Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated With Virologic Failure.

Abstract: BACKGROUND Previously reported post hoc multivariable analyses exploring predictors of confirmed virologic failure (CVF) with cabotegravir + rilprivirine long-acting (CAB + RPV LA) were expanded to include data beyond Week 48, additional covariates, and additional participants. METHODS Pooled data from 1651 participants were used to explore dosing regimen (every 4 or every 8 weeks), demographic, viral, and pharmacokinetic covariates as potential predictors of CVF. Prior dosing regimen experience was accounted for using two populations. Two models were conducted in each population - baseline factor analyses exploring factors known at baseline, and multivariable analyses exploring baseline factors plus post-baseline model-predicted CAB/RPV trough concentrations (4 and 44 weeks post injection). Retained factors were evaluated to understand their contribution to CVF (alone or in combination). RESULTS Overall, 1.4% (n = 23/1651) of participants had CVF through 152 weeks. The presence of RPV resistance-associated mutations (RAMs), HIV-1 subtype A6/A1, and body mass index (BMI) ≥ 30 kg/m2 were associated with an increased risk of CVF (p < 0.05 adjusted incidence rate ratio), with participants with ≥2 of these baseline factors having a higher risk of CVF. Lower model-predicted CAB/RPV troughs were additional factors retained for multivariable analyses. CONCLUSIONS The presence of ≥2 baseline factors (RPV RAMs, A6/A1 subtype, and/or BMI ≥30 kg/m2) was associated with increased CVF risk, consistent with prior analyses. Inclusion of initial model-predicted CAB/RPV trough concentrations (≤1st quartile) did not improve the prediction of CVF beyond the presence of a combination of ≥2 baseline factors, reinforcing the clinical utility of the baseline factors in the appropriate use of CAB + RPV LA.

Hepmarc: A 96 week randomised controlled feasibility trial of add-on maraviroc in people with HIV and non-alcoholic fatty liver disease

Abstract: Objectives Maraviroc may reduce hepatic inflammation in people with HIV and non-alcoholic fatty liver disease (HIV-NAFLD) through CCR5-receptor antagonism, which warrants further exploration. Methods We performed an open-label 96-week randomised-controlled feasibility trial of maraviroc plus optimised background therapy (OBT) versus OBT alone, in a 1:1 ratio, for people with virologically-suppressed HIV-1 and NAFLD without cirrhosis. Dosing followed recommendations for HIV therapy in the Summary of Product Characteristics for maraviroc. The primary outcomes were safety, recruitment and retention rates, adherence and data completeness. Secondary outcomes included the change in Fibroscan-assessed liver stiffness measurements (LSM), controlled attenuation parameter (CAP) and Enhanced Liver Fibrosis (ELF) scores. Results Fifty-three participants (53/60, 88% of target) were recruited; 23 received maraviroc plus OBT; 89% were male; 19% had type 2 diabetes mellitus. The median baseline LSM, CAP & ELF scores were 6.2 (IQR 4.6–7.8) kPa, 325 (IQR 279–351) dB/m and 9.1 (IQR 8.6–9.6) respectively. Primary outcomes: all individuals eligible after screening were randomised; there was 92% (SD 6.6%) adherence to maraviroc [target >90%]; 83% (95%CI 70%-92%) participant retention [target >65%]; 5.5% of data were missing [target <20%]. There were noo Serious Adverse Reactions; mild-moderate intensity Adverse Reactions were reported by five participants (5/23, 22% (95%CI 5%-49%)) [target <10%]. All Adverse Reactions resolved. Secondary outcomes: no important differences were seen by treatment group for the change from baseline in LSM, CAP or ELF scores Conclusions This feasibility study provides preliminary evidence of maraviroc safety amongst people with HIV-NAFLD, and acceptable recruitment, retention, and adherence rates. These data support a definitive randomised-controlled trial assessing maraviroc impact on hepatic steatosis and fibrosis. Trial registration Clinical trial registry: ISCRTN, registration number 31461655.

Experiences of initiating rapid antiretroviral therapy among people newly diagnosed with HIV in East London: a qualitative study

Abstract: Objectives We aimed to explore the experiences of people who initiated rapid antiretroviral therapy (ART) within 7 days of HIV diagnosis, as part of routine care in London. Methods Using purposive sampling, 18 in-depth, semistructured interviews were conducted between December 2020 and September 2021 with people who started rapid ART at Barts Health NHS Trust. Participants aged 22–69 years included 15 cisgender men and three cisgender women. Five identified as heterosexual and 13 as gay and bisexual and other men who have sex with men. Ethnic identities: six White Non-UK, five White UK, three Black Caribbean, two South Asian and two East Asian. Interviews explored feelings about the new HIV diagnosis, attitudes to rapid ART including barriers to and facilitators of starting. Thematic analysis of transcribed interviews was undertaken. Results Four themes were identified: (1) being offered rapid ART is acceptable; (2) it is a way of taking control of their health; (3) the need for information and support and (4) an individualised approach to care. Reasons for starting included getting well, staying well and reducing the likelihood of passing on HIV. Facilitators included being given comprehensive information about treatment and managing potential side-effects and a supportive clinical team. Support specified included a non-judgemental attitude, approachability, reassurance, encouragement and information about peer support. Most participants expressed they could not understand why people would not begin treatment, but suggested needing more time to decide and denial of diagnosis as possible barriers. Conclusions To our knowledge, this is the first qualitative study exploring the experiences of people initiating rapid ART in the UK. It was deemed acceptable to an ethnically diverse, predominantly male sample of people newly diagnosed with HIV. Future research should include strategies to recruit a more gender diverse sample and those who declined or stopped rapid ART.