Ciclosporin A Proof of Concept Study in Patients with Active, Progressive HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis

HTLV-1 is a retrovirus transmitted through body fluids that is commonly seen in the West Indies, South America and Southern Japan but rarely in the UK. Although most patients remain healthy carriers, HTLV-1 causes serious conditions such as adult T cell leukaemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). The infection which is life-long cannot be eradicated and treatments for the associated diseases are limited. We report the encouraging findings of the first UK Medical Research Council funded treatment study for patients with early and/or deteriorating HAM/TSP. Treatment with ciclosporin A, a drug commonly used to dampen the immune system in transplant patients, was investigated. Symptoms and signs of disease, particularly low back pain and muscle stiffness, improved by week 24 and in some patients this improvement persisted after the 48 weeks of treatment, at least to the end of the study at week 72. Most striking was the finding that the amount of HTLV-1 in the fluid around the spinal cord, called cerebrospinal fluid, was reduced during treatment. These findings justify the further study of ciclosporin A in patients with HAM/TSP

Examining oral pre-exposure prophylaxis (PrEP) literacy among participants in an HIV vaccine trial preparedness cohort study

Background: PrEP literacy is influenced by many factors including the types of information available and how it is interpreted. The level of PrEP literacy may influence acceptability and uptake. Methods: We conducted 25 in-depth interviews in a HIV vaccine trial preparedness cohort study. We explored what participants knew about PrEP, sources of PrEP knowledge and how much they know about PrEP. We used the framework approach to generate themes for analysis guided by the Social Ecological Model and examined levels of PrEP literacy using the individual and interpersonal constructs of the SEM. Results: We found that PrEP awareness is strongly influenced by external factors such as social media and how much participants know about HIV treatment and prevention in the local community. However, while participants highlighted the importance of the internet/social media as a source of information about PrEP they talked of low PrEP literacy in their communities. Participants indicated that their own knowledge came as a result of joining the HIV vaccine trial preparedness study. However, some expressed doubts about the effectiveness of the drug and worried about side effects. Participants commented that at the community level PrEP was associated with being sexually active, because it was used to prevent the sexual transmission of HIV. As a result, some participants commented that one could feel judged by the health workers for asking for PrEP at health facilities in the community. Conclusion: The information collected in this study provided an understanding of the different layers of influence around individuals that are important to address to improve PrEP acceptability and uptake. Our findings can inform strategies to address the barriers to PrEP uptake, particularly at structural and community levels. Trial registration: https://clinicaltrials.gov/ct2/show/NCT0406688

β₂ microglobulin a marker of inflammation in peripheral venous blood (0–72 weeks).

<p>β₂ microglobulin a marker of inflammation in peripheral venous blood (0–72 weeks).</p

Magnetic resonance imaging of the thoracic chord (0–72 weeks).

<p>Clinical improvement was observed despite the marked atrophy of the thoracic cord.</p

Log¹⁰ HTLV-1 proviral DNA in peripheral blood mononuclear cells (PBMCs) (0–72 weeks).

<p>Log¹⁰ HTLV-1 proviral DNA in peripheral blood mononuclear cells (PBMCs) (0–72 weeks).</p

Log₁₀ HTLV-1 proviral DNA (blood) (copies/100 PBMCs): 0–48 weeks whilst on CsA treatment; 49–72 weeks without treatment.

<p>Log₁₀ HTLV-1 proviral DNA (blood) (copies/100 PBMCs): 0–48 weeks whilst on CsA treatment; 49–72 weeks without treatment.</p

Log₁₀ HTLV-1 proviral DNA (CSF): −2 is baseline evaluation and week 12 CSF was collected while on CsA treatment.

<p>Log₁₀ HTLV-1 proviral DNA (CSF): −2 is baseline evaluation and week 12 CSF was collected while on CsA treatment.</p

Flowchart of enrolment and follow up of patients with definite and early and/or progressing HAM/TSP.

<p>50 patients with HAM/TSP were identified and 9 were identified as patients with early and/or deteriorating HAM/TSP, 7 of whom consented to treatment with ciclosporin A. Two patients chose to re-start ciclosporin A after 48 weeks during trial period.</p

T cell activation marker: absolute CD4⁺/CD25⁺ T cell count (0–72 weeks).

<p>T cell activation marker: absolute CD4⁺/CD25⁺ T cell count (0–72 weeks).</p

Therapeutic drug monitoring of ciclosporin A: dosing and through CsA plasma concentrations.

<p>Therapeutic drug monitoring of ciclosporin A: dosing and through CsA plasma concentrations.</p