The purpose of this study is to examine whether the co-administration of valproic acid (Epival®), with highly active antiretroviral therapy (HAART) can reduce the size of HIV latent reservoirs in infected CD4 cells.

Participants must be on HAART with a suppressed viral load (< 50 copies/ml) for at least the previous 12 months. They will be randomly assigned to one of two groups, one group will start the valproic acid right away at week 1 for 16 weeks, and the other group will wait until week 17 to add valproic acid to their treatment for 32 weeks. Subjects will be followed every four weeks for one year and evaluated by a variety of assays, all carried out using well-established methods, to assess the main outcome defined by changes in HIV reservoir size measured by the mean frequency of resting CD4 memory cells carrying HIV proviral DNA.

Inclusion Criteria:

Documented HIV seropositive infection by Western Blot, EIA assays or viral load.

• Aged 18 years old or older.
• Viral load <50 copies/ml for at least the previous 12 months.
• Circulating CD4+ cell count ³ 200 cells/ml.
• Taking HAART.
• Vital signs, physical examination and laboratory results do not exhibit evidence of diseases such as advanced cirrhosis and advanced liver disease (ALT or AST > 5 x upper limit of normal value).
• Karnofsky performance status 80%.
• Subject does not require and agrees not to take, for the duration of the study, any medication that is contraindicated with VPA.
• Willing and able to give informed consent.
• All participants will agree to abstinence or to used effective methods of contraception while on the study.

Exclusion Criteria:

• Pregnant or breast-feeding women.
• Psychiatric or cognitive disturbance or illness that could preclude compliance with the study.
• Current use or use within four weeks prior to the baseline visit, of cytotoxic agents, systemic corticosteroids or any immunomodulatory agents such as intravenous immunoglobulin, or hydroxyurea.
• HIV vaccine within six months of screening visit
• Allergic reaction to VPA.
• Active intravenous drug users.
• History of bleeding disorders.
• Unstable or treated hypertension.
• Past-history of pancreatitis or chronic liver disease (ALT or AST > 5 x upper limit of normal value). However subject co-infected with hepatitis B or C can participate if ALT or AST is < 5 x upper limit of normal value.
• Renal failure (creatinine > 2 x upper limit of normal value).
• Ammonemia (> 2x upper limit of normal value).
• Taking Zidovudine (AZT), or combination of drugs containing AZT like Combivir or Trizivir. However this subject will be asked to switch to another NRTI,at least two weeks prior to Valproic Acid initiation, to become eligible.
• Taking on daily basis: phenytoin, carbamazepine, phenobarbital, warfarin or aspirin.
• Subject has any of the following abnormal laboratory results Hemoglobin < 100 g/L. Absolute neutrophil count < 0.75 x 10 9 cells/L. Platelet count < 50 x 10 9 cells/L.
• Subject suffering from urea cycle disorders.