First ohm20, I see you are a biotech investor in many stocks. Good to have you onboard here.
Now, the biggest obstacle for them with mono is IV every week or two weeks; there study tried both. They are not going to have a large market. I'm surprised they would get trial approval above the unmet need category at this point. Similar to IZ, requiring IV, they didn't attempt mono.
Here is one of their patents with the 'functional cure' explanation. Maybe we should steal that language. Leronlimab provides a function cure. We already have the ccr5 connection to the actual cure, maybe it will catch on.
https://patents.google.com/patent/EP3194442A1/en
Treatment and functional cure of hiv infection by monoclonal antibodies to cd4 mediating competitive hiv entry inhibition
Now, the biggest obstacle for them with mono is IV every week or two weeks; there study tried both. They are not going to have a large market. I'm surprised they would get trial approval above the unmet need category at this point. Similar to IZ, requiring IV, they didn't attempt mono.
Here is one of their patents with the 'functional cure' explanation. Maybe we should steal that language. Leronlimab provides a function cure. We already have the ccr5 connection to the actual cure, maybe it will catch on.
https://patents.google.com/patent/EP3194442A1/en
Treatment and functional cure of hiv infection by monoclonal antibodies to cd4 mediating competitive hiv entry inhibition
Quote:
Two curative strategies, sterilizing (i.e., eradication) and functional cures, as shown in Table 1, are currently being investigated for HIV infection. The sterilizing cure method aims to eliminate all HIV-infected cells, completely purging HIV from the body and is defined as one that reduces viral loads to less than 1 copy per milliliter of blood. A functional cure aims for a remission state and long-term control of HIV, including low viral loads in the absence of antiretroviral therapy and in one that reduces viral loads to less than 50 copies per milliliter of blood, either permanently or for an extended period of time.
The only current example of a "sterilizing cure" is from a case study of a man nicknamed "The Berlin Patient" with HIV infection, who had acute myeloid leukemia and received a bone marrow transplant from a donor with a mutated or alternate form of the CCR5 gene. After 45 months without treatment, doctors have been unable to detect HIV in his system. Nonetheless, a strategy of using bone marrow transplantation with a CCR5 mutant donor is not a realistic cure for HIV given the toxicity and complexity of the treatment. One natural example of a "functional cure" can be found in elite controllers. Elite controllers are individuals infected with HIV whose immune systems are able to naturally control the virus without antiretroviral drugs. These individuals successfully maintain stable CD4 (white blood) cell counts, low or undetectable viral loads and a significantly smaller amount of "latent HIV" in their cells.
One major obstacle to a cure is the fact that there are "latent HIV reservoirs" that lie dormant in immune system cells, such as memory cells, with long life-spans during antiretroviral drug treatment as such treatment can work on active viral infection by blocking replication but not on latent HIV. However, if such anti-retroviral drug treatment is stopped, latent HIV may be activated, renewing the HIV infection process.
Current strategies to target these "problematic" latent HIV reservoirs include efforts to deplete latent reservoirs through activation of virus expression in the presence of HAART treatment resulting in the killing-off of infected cells leaving only uninfected cells behind. One group of activators is histone deacetylase (HDAC) inhibitors as illustrated in Table 2. Currently, HDAC inhibitors are used as mood stabilizers, anti-epileptic drugs and anti-cancer treatments. The long-term impact of HDAC inhibitors on enhancing the risk of malignancy and/or reactivation of oncogenes remains a major concern. This strategy is viable if active viral replication is completely inhibited with combination antiretroviral therapy (cART). So far, these efforts have not yielded long term virus suppression or functional cures.
Two plans for restricting or reducing the size of latent HIV reservoirs in people with HIV infection involve (1) intensification treatment by addition of new ART drug to a person's regimen and (2) early treatment by starting ART immediately after infection. Results from several studies have shown that the number of HIV-infected cells decreases significantly when cART is initiated during the early acute stage rather than the chronic late stage of HIV infection.
In summary, potent and safe agents would be highly desirable for use in HIV treatment either alone or as an adjunct to cART provided that they can (1) block HIV entry, in both cell- free and cell-to-cell transmission modes, leading to significant reduction of HIV infection in activated or resting CD4 T-cells including those long-lived memory T cells; (2) specifically reactivate HIV infected resting CD4 T-cells to release HIV leading to apoptosis in latently infected cells; and/or (3) inhibit HIV infected resting CD4 T-cell activation/inflammation upon antigen/cytokine stimulation, when such activation can cause pyroptosis and massive depletion of normal CD4 positive T-cells leading to AIDS. A concerted effort towards a functional or sterilizing cure for HIV infection leading to long- term or permanent remission in the subsequent absence of cART is high on the global public health agenda and is being actively explored worldwide and, when available, will revolutionize the treatment of HIV infection
