P7-17. Safety and efficacy of the GnRH analouge buserelin in HIV treatment; a phase IIa study

Ola Winqvist [1], Hans-Friedemann Kinkel [2], Petra Jones [3], Hans Glise [3]
Affiliates: [1] Department of Medicine, Karolinska Institutet, Stockholm, Sweden. [2] Department of Family Medicine, University of Pretoria, Pretoria, South Africa. [3] Immune System Regulation Holding AB, Stockholm, Sweden.

Background
Gonadotrophin releasing hormone (GnRH) can affect the immune system by binding to GnRH receptors on immune cells. We wanted to evaluate safety and efficacy of a novel treatment of HIV with the GnRH analogue buserelin. The aim was to assess the ability of buserelin to increase antigen presentation of HIV and cause specific immune activation.

Methods
Twenty-six asymptomatic, treatment-naïve HIV infected adult men were included in a phase IIa clinical trial. Patients were treated with intranasal buserelin (1.2 mg/day) for four weeks. After seven days, the patients were injected with a single intramuscular testosterone depot injection (150 mg) to prevent buserelin related endocrine effects. Patients were followed by weekly laboratory assessments; Testosterone, FSH, LH, HIV viral load, CD4 and CD8 cells counts and immune cell activation. After 36-40 months, an ad hoc follow-up study was conducted in thirteen of the patients.

Results
No severe adverse events were reported. Expression levels of HLA class I and CD69 were significantly increased on CD4+ and CD8+ T cells after treatment. Also, the frequency of CD25+CD8+ T effector cells was increased. Furthermore, the patients displayed a reduction in HIV viral load that further decreased four weeks after discontinuation of treatment. In the follow-up study six of the thirteen patients showed no progression of HIV viral load, indicating that GnRH has positive long-term effects.

Conclusions
GnRH treatment of HIV infected patients is safe and well tolerated and leads to immune activation and reduced HIV viral load.