A5366: Selective Estrogen Receptor Modulators to Enhance the Efficacy of Viral Reactivation with Histone Deacetylase Inhibitors

While antiretrovirals known as ARV’s (group of medicines used to treat HIV) have provided very effective treatment of HIV, cure of HIV from the body has not been possible.  One of the reasons may be due to virus hiding in resting (or ‘latent’) immune cells. This reservoir (the hidden virus) is able to reproduce itself and serves as source of infection if ARV’s are stopped. Some investigational medications have been shown to wake up latent (sleeping) immune cells allowing them to get rid of the virus they have inside them. However, these therapies are only partly effective and results vary in different people. Preliminary studies have shown that these therapies may be less effective in women due to female hormones.

This study will evaluate one of the medications (Vorinostat) that have been shown to reverse latency in combination with another medication (Tamoxifen) that researchers hope will enhance that effect, specifically in women.

The primary purpose of this study is to see if Tamoxifen given with Vorinostat is safe. It will also study if Tamoxifen will enhance the ability of Vorinostat to reverse latency in post-menopausal women.

• HIV-1 positive women between 18 and 65 years of age (up to 66^th birthday)
• Post-menopausal (either >18 with both ovaries removed or >40 with no period in the last 2 years)
• CD4 count >300 cells/mm³ (CD4 cells are a kind of white blood cell that are a measure of the immune system)
• On ARV’s for at least 2 years with undetectable viral loads
• No active Hepatitis B or C
• No history of cancer, blood clot or stroke
• Not currently smoking or taking hormonal therapy

At entry, participants will be randomized to receive open label Tamoxifen 20mg by mouth daily (20 participants), or no Tamoxifen (10 participants) for the first 5 weeks. All participants will then receive 2 doses of 400mg each Vorinostat by mouth separated by 72 hours.

Up to 9 weeks per participant after a screening period of up to 90 days.