BIT225: HIV VPU Inhibitor Candidate

Contender in the Ring
A novel HIV therapy targets & eradicates one cell type in the viral reservoir
by Jeannie Wraight

BIT225, an HIV VPU inhibitor, has demonstrated strong immunological effects and the ability to effectively render activated macrophages (from viral reservoirs) unable to replicate. Results from a Phase II study from Thailand established BIT225 to be (thus far) a contender as part of an HIV cure strategy.

As described previously in Destination: Cure, HIV hides in clusters of cells called viral reservoirs where they remain inactive indefinitely. As these cells are not producing HIV, they are not recognized as a threat by the immune system. HIV antiretrovirals (ARVs) are unable to penetrate these latently infected cells. Latent HIV has the potential to awaken and begin reproducing. If a person who is on ARVs and virally suppressed stops taking their ARVs or becomes drug-resistant, latently infected cells can awaken, resulting in viral rebound. It takes only one latently infected cell for this to occur.

Researchers have found latent HIV in several types of cells, including resting T cells, follicular dendritic cells, and macrophages. Macrophages are long-lived cells derived from monocytes that can reside in tissue in several places throughout the body, including the liver, lungs, brain and bone marrow. Macrophages engulf viruses, bacteria, fungi and dead cells in a process called phagocytosis.

BIT225 works by targeting the protein in HIV that is responsible for viral assembly, interfering with its ability to properly replicate. With HIV replication incompetent, the virus is unable to infect additional cells.

Researchers conducted a Phase II study at two sites in Thailand to discover if adding BIT225 to an ARV regimen produced additional virological and immunological benefit beyond that of ARVs alone.

BIT225-009 enrolled twenty-seven patients and analyzed whether BIT225, in addition to Atripla, showed a benefit over Atripla and placebo. All study participants were treatment naive. The study ran for twelve weeks and all participants remained on ARVs after the study concluded. Researchers focused on safety pharmacokinetics and the impact on virological and immunological markers.

A statistically significant benefit was seen in those on BIT225 and Atripla versus those on Atripla and placebo in CD8+ and activated CD4 T cell populations. This difference in these levels is evidence of the immune system recognizing and responding to the replication-incompetent virus as a foreign invader thus producing an immune response to eliminate the perceived threat.

According to the poster authors: ”The commencement of a decline of activated CD4+ cell levels at week 6 suggests that virus from these reservoir cells is being eradicated, and cleared by week 12 when levels return to those seen in the ART + placebo group.”

Researchers looked at changes in the levels of Soluble CD163 (sCD163), a macrophage immune marker. High levels of sCD163 are seen prior to initiating ARVs, but decrease once viral suppression had occurred. However, this is not the case with all HIV-positive individuals. High levels of this immune marker in people living with HIV with well controlled viremia are linked to an increased risk of morbidity and mortality. Study participants taking BIT225 with Atripla experienced a greater decrease in sCD163 than those on Atripla and placebo. According to the poster authors, the ability of BIT225 to show a greater decrease of this immune marker in people living with HIV may show cause for use of BIT225 in high-risk patients.

The importance of this immune marker was further evidenced in a separate study (not involving BIT225) in people co-infected with HIV and HCV. In this study, sCD163 levels decreased when participants began ARVs, but did not normalize. In those co-infected with HIV and HCV, sCD163 was linked to the progression of fibrosis.
BIT225 was found to be safe with no serious adverse events (AEs). The most common minor AEs were dizziness at thirteen percent for those on BIT225 and Atripla versus eight percent for Atripla and placebo; headache at nine percent for BIT225 and Atripla versus two percent for Atripla and placebo; and nausea at six percent for BIT225 and Atripla versus six percent for Atripla and placebo.

The results of this study indicate that BIT225 may play a role as part of a potential cure regimen if its demonstrated ability to eradicate HIV from macrophages is further shown in additional studies. It also shows promise as an HIV therapeutic, particularly in high-risk individuals.

It’s important to realize that this therapy is not produced by Big Pharma. It is currently owned by a small Australasian Biotech company (Biotron) that, as with most biotechs, has limited funds for further studies. Advocacy is needed to ensure continued research of this drug with support by the NIH, AIDS Clinical Trials Group, and other funding mechanisms.

Jeannie Wraight is the former editor-in-chief and co-founder of HIV and HCV Haven ( and a blogger and writer for She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in New York City.