Stable HIV Reservoir Despite Prolonged Low-Dose Mycophenolate to Limit CD4+ T-cell Proliferation.

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• The persistent HIV reservoir in CD4+ T cells is a major obstacle to achieving a cure.
• CD4+ T-cell proliferation maintains this reservoir, even during effective antiretroviral therapy (ART).
• Inhibiting T-cell proliferation is a potential strategy to deplete the HIV reservoir.

Purpose of the Study:

• To evaluate the efficacy of mycophenolate, a T-cell antiproliferative agent, in reducing the HIV reservoir.
• To assess the impact of mycophenolate on total and intact HIV DNA levels in individuals with HIV on suppressive ART.

Main Methods:

• An unblinded, uncontrolled clinical trial was conducted involving individuals with HIV on chronic ART.
• Mycophenolate dosage was determined by ex vivo antiproliferative effects.
• The primary outcome measured was a reduction in HIV DNA in blood over 48 weeks.

Main Results:

• Four participants completed the 48-week protocol, with no significant reduction in total or intact HIV DNA observed.
• No changes in CD4+ T-cell subset composition within the HIV reservoir or the overall CD4+ T-cell population were detected.
• While an ex vivo antiproliferative effect was noted shortly after dosing, it diminished significantly by the drug trough.

Conclusions:

• Mycophenolate treatment over 48 weeks did not effectively reduce the size or composition of the HIV reservoir.
• The antiproliferative effect of mycophenolate may not be sufficient or sustained enough to impact the latent HIV reservoir in vivo.
• This study suggests that mycophenolate is not a viable strategy for depleting the HIV reservoir.