Study protocol: the ILANA study - exploring optimal implementation strategies for long-acting antiretroviral therapy to ensure equity in clinical care and policy for women, racially minoritised people and older people living with HIV in the UK - a qualitative multiphase longitudinal study design.

INTRODUCTION: Cabotegravir and rilpivirine (CAB+RPV long-acting (LA)) is recommended as a treatment for HIV-1 allowing people living with HIV to receive 2 monthly injectable treatment, rather than daily pills. Providing injectable therapy in a system designed to provide and manage study participants on oral treatments poses logistical challenges namely how resources are used to accommodate patient preference within constrained health economies with capacity limitations. In this pragmatic multicentre study, we aim to understand the implementation of CAB-RPV-LA administration in two settings via mixed methods to explore perspectives of participants and the clinical team delivering CAB+RPV LA. METHODS AND ANALYSIS: Women, racially minoritised people and older people are chronically under-represented in HIV clinical trials so the ILANA trial has set recruitment caps to ensure recruitment of 50% women, 50% ethnically diverse people and 30% over 50 years of age to include a more representative study population. Using a mixed-methods approach, the primary objective is to identify and evaluate the critical implementation strategies for CAB+RPV LA in both hospital and community settings. Secondary objectives include evaluating feasibility and acceptability of CAB+RPV LA administration at UK clinics and community settings from the perspective of HIV care providers, nurses and representatives at community sites, evaluating barriers to implementation, the utility of implementation strategies and adherence. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Health Research Authority Research Ethics Committee (REC reference: 22/PR/0318). The dissemination strategy has been formulated with the SHARE Collaborative Community Advisory Board to maximise the impact of this work on clinical care and policy. This strategy draws on and leverages existing resources within the participating organisations, such as their academic infrastructure, professional relationships and community networks. The strategy will leverage the Public Engagement Team and press office to support dissemination of findings. TRIAL REGISTRATION NUMBER: NCT05294159.

Neutralization activity in a geographically diverse East London cohort of human immunodeficiency virus type 1-infected patients: clade C infection results in a stronger and broader humoral immune response than clade B infection.

The array of human immunodeficiency virus (HIV) subtypes encountered in East London, an area long associated with migration, is unusually heterogeneous, reflecting the diverse geographical origins of the population. In this study it was shown that viral subtypes or clades infecting a sample of HIV type 1 (HIV-1)-positive individuals in East London reflect the global pandemic. The authors studied the humoral response in 210 treatment-naïve chronically HIV-1-infected (>1 year) adult subjects against a panel of 12 viruses from six different clades. Plasmas from individuals infected with clade C, but also plasmas from clade A, and to a lesser degree clade CRF02_AG and CRF01_AE, were significantly more potent at neutralizing the tested viruses compared with plasmas from individuals infected with clade B. The difference in humoral robustness between clade C- and B-infected patients was confirmed in titration studies with an extended panel of clade B and C viruses. These results support the approach to develop an HIV-1 vaccine that includes clade C or A envelope protein (Env) immunogens for the induction of a potent neutralizing humoral response.

Early virologic failure in HIV-1 infected subjects on didanosine/tenofovir/efavirenz: 12-week results from a randomized trial.

OBJECTIVE: To compare the safety and efficacy of two once-daily antiretroviral regimens containing lamivudine (3TC) or tenofovir disoproxil fumarate (TDF), each administered with didanosine (ddI) and efavirenz (EFV) as initial therapy to HIV-1-infected subjects. METHODS: Single centre, randomized (1: 1), open-label study in antiretroviral-naive, HIV-infected adults. Subjects commenced either 3TC/ddI/EFV (3TC group) or TDF/ddI/EFV (TDF group). Safety, Medication Event Monitoring System (MEMScap) and plasma EFV concentration monitoring was performed over the study period. Comparisons between groups were assessed using chi test and linear regression analysis was used to assess the relationship between EFV concentrations and virological response. RESULTS: Seventy-seven subjects were enrolled prior to recruitment being suspended, 36 to the 3TC group and 41 to the TDF group. Intention-to-treat analysis in which last observation carried forward (LOCF) found the mean viral log10 load [95% confidence interval (CI)] at weeks 4 and 12 to be 2.67 (2.47-2.87) and 1.83 (1.74-1.92) for the 3TC group and 2.75 (2.45-3.05) and 2.28 (1.96-2.6) for the TDF group (P = 0.013). Emergence of resistance occurred in five of 41 (12.2%) subjects in the TDF group up to week 12 compared with none of 36 in the 3TC group, (P < 0.05); these five subjects shared similar baseline characteristics (CD4+ cell counts < 200 x 10 cells/l and HIV-1 RNA > 100,000 copies/ml). Despite MEMScap monitoring showing > 99% adherence in all subjects, among the five failures, three had low EFV concentrations. CONCLUSION: TDF/ddI/EFV as initial therapy appears to have diminished efficacy in subjects with CD4 < 200 x 10 cells/l and viral load > 100,000 copies/ml. Treatment failure with resistance was not attributable to baseline resistance, efavirenz exposure or poor adherence.