Acceptability, feasibility and costs of universal offer of rapid point of care testing for HIV in an acute admissions unit: results of the RAPID project.

OBJECTIVES: UK guidance recommends that acute medical admissions are offered an HIV test. Our aim was to determine whether a dedicated staff member using a multimedia tool, a model found effective in the USA, is an acceptable, feasible, and cost-effective model when translated to a UK setting. METHODS: Over 4 months in 2010, a health advisor (HA) approached 19-65-year-olds at a central London acute medical admissions unit and offered a rapid HIV point of care test (POCT) with the aid of an educational video. Feasibility and acceptability were assessed through surveys and uptake rates. Costs per case of HIV infection identified were established. RESULTS: Of the 606 eligible people admitted during the pilot, 324 (53.5%) could not be approached or were individuals for whom testing was deemed inappropriate. In total, 23.0% of eligible admissions had an HIV POCT. Of the patients who watched the video and had not recently been tested for HIV, 93.6% (131 of 140) agreed to an HIV test; four further patients had an HIV test but did not watch the video. Three tests (2.2%; three of 135) were reactive and all were confirmed HIV positive on laboratory testing. HIV testing in this setting was felt to be appropriate by 97.5% of individuals. The cost per patient was £21, and the cost per case of HIV identified was £1083. CONCLUSIONS: Universal POCT HIV testing in an acute medical setting, facilitated by an educational video and dedicated staff, appears acceptable, feasible, effective, and low cost. These findings support the recommendation of HIV testing for all medical admissions in high-prevalence settings, although with this model a significant proportion remained untested.

The Safety and Immunogenicity of GTU®MultiHIV DNA Vaccine Delivered by Transcutaneous and Intramuscular Injection With or Without Electroporation in HIV-1 Positive Subjects on Suppressive ART.

Previous studies have shown targeting different tissues via the transcutaneous (TC) and intramuscular injection (IM) with or without electroporation (EP) has the potential to trigger immune responses to DNA vaccination. The CUTHIVTHER 001 Phase I/II randomized controlled clinical trial was designed to determine whether the mode of DNA vaccination delivery (TC+IM or EP+IM) could influence the quality and function of induced cellular immune responses compared to placebo, in an HIV positive clade B cohort on antiretroviral therapy (ART). The GTU®MultiHIV B DNA vaccine DNA vaccine encoded a MultiHIV B clade fusion protein to target the cellular response. Overall the vaccine and regimens were safe and well-tolerated. There were robust pre-vaccination IFN-γ responses with no measurable change following vaccination compared to placebo. However, modest intracellular cytokine staining (ICS) responses were seen in the TC+IM group. A high proportion of individuals demonstrated potent viral inhibition at baseline that was not improved by vaccination. These results show that HIV positive subjects with nadir CD4+ counts ≥250 on suppressive ART display potent levels of cellular immunity and viral inhibition, and that DNA vaccination alone is insufficient to improve such responses. These data suggest that more potent prime-boost vaccination strategies are likely needed to improve pre-existing responses in similar HIV-1 cohorts (This study has been registered at http://ClinicalTrials.gov under registration no. NCT02457689).

Combined skin and muscle vaccination differentially impact the quality of effector T cell functions: the CUTHIVAC-001 randomized trial.

Targeting of different tissues via transcutaneous (TC), intradermal (ID) and intramuscular (IM) injection has the potential to tailor the immune response to DNA vaccination. In this Phase I randomised controlled clinical trial in HIV-1 negative volunteers we investigate whether the site and mode of DNA vaccination influences the quality of the cellular immune responses. We adopted a strategy of concurrent immunization combining IM injection with either ID or TC administration. As a third arm we assessed the response to IM injection administered with electroporation (EP). The DNA plasmid encoded a MultiHIV B clade fusion protein designed to induce cellular immunity. The vaccine and regimens were well tolerated. We observed differential shaping of vaccine induced virus-specific CD4 + and CD8 + cell-mediated immune responses. DNA given by IM + EP promoted strong IFN-γ responses and potent viral inhibition. ID + IM without EP resulted in a similar pattern of response but of lower magnitude. By contrast TC + IM (without EP) shifted responses towards a more Th-17 dominated phenotype, associated with mucosal and epidermal protection. Whilst preliminary, these results offer new perspectives for differential shaping of desired cellular immunity required to fight the wide range of complex and diverse infectious diseases and cancers.

Genital ulcers: it is not always simplex .

Patients with vulval aphthae, also termed Lipschütz ulcers, often present to genitourinary medicine clinics. Typically, these ulcers present as acute, painful, vulval ulcers in young women and adolescents. The aetiology is unknown, and often these ulcers are accompanied by flu-like symptoms. Previous case reports have linked such lesions to acute viral infections such as Epstein-Barr virus, cytomegalovirus and influenza A. We report the first case of influenza B virus and adenovirus infections associated with this presentation.