Keywords: HAART Improve, Interaction with other drugs, Venture of HIV cure, Safety concerns
The dose of Efavirenz was reduced and found equally effective with lesser side effects. Many newer molecules are on the pipeline. But in spite of all these, the long awaiting sterilized cure is getting delayed. The sterilized cure would no doubt be beneficial as it will certainly reduce morbidity, mortality, new infections, economic burden of the individuals and their countries, adverse effects due to the lifelong exposure to drugs, acceleration of ageing etc. The main barrier to a sterilizing cure is the presence of a ‘latent reservoir’; a population of HIV infected cells that persist for the lifetime of the individual despite ART and the HIV specific immune response [1,2]. So, the identification of various sources of viral reservoirs like Latent CD4 cells, CNS-microglial cells, macrophages, monocytes- (Peripheral Blood Mononuclear cells), reproductive system, lymph nodes, spleen and gut tissues get the prime importance in the research .
- Be able to live a normal, healthy lifespan
- Be off antiretroviral therapy or any other HIV-related medications
- Be incapable of transmitting the virus to others
- Hit early Hit hard: Early starting the treatment before the establishment of latent reservoir.
- Kick and kill or Shock and Kill: Flushing the reservoir cells into the blood stream and made the virus susceptible for ART or immune mechanism.
- Keep the reservoir to be inactive and remain dormant for ever.
- Now they identified an enzyme called as Histone Deacetylase (HDAC) which is responsible to keep up latency. Several companies are looking into HDAC-Inhibitors. Some in vitro HDAC studies seemed to be promising but yet to be confirmed by clinical studies. Flush these latent CD4 HIV infected cells with drugs like Vorinostat and Panobinostat (HDAC inhibitors) into the circulation. Make susceptible for ART after expressed out of these reservoirs .
- Histone Deacetylase Inhibitors (HDI) have a broad spectrum of epigenetic activities. Vorinostat is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL) when the disease persists, gets worse, or comes back during or after treatment with other medicines .
The combination of injectable antiviral therapy soon after the infection and vesatolimod (a novel immune-activating drug) quickly suppressed viral load and delayed antibody responses to the virus in a monkey study, suggesting a possible role for vesatolimod in a cure strategy.
Scientists working towards cure are trying to better describe the ‘latent reservoir’ of HIV DNA in elite controllers-individuals living with HIV who control HIV replication without taking antiretroviral therapy-in order to understand these individuals’ natural control of the virus. They reported that elite controllers have low levels of intact provirus (virus able to replicate) and these are associated with having receptor molecules on the surface of their immune cells that are less responsive to HIV infection .
An intravenous post-attachment inhibitor is approved for treatment of multidrug-resistant HIV infection
Ibalizumab is a humanized monoclonal antibody that binds to CD4 on human cells and thereby prevents HIV entry (a CD4-directed post attachment inhibitor). The medication was approved on March 6, 2018, for treatment of multidrug-resistant HIV in adults failing Anti-Retroviral Therapy (ART).
In a phase 3 trial, 40 heavily treatment experienced patients with resistance to three antiretroviral drug classes, but with at least one active remaining drug, were enrolled in a single-arm trial. Following a loading dose of ibalizumab, 83% of participants had a ≥0.5 log drop in HIV RNA level. After receiving the loading dose, participants had optimization of their regimen with addition of other antiretroviral agents, including at least one active drug and ibalizumab was continued every 2 weeks. At week 25, 50% of participants had HIV RNA levels
Ibalizumab is given as a single 2000mg loading dose (infused over at least 30 min) followed by a maintenance dose of 800 mg every 2 weeks (infused over at least 15 min). Patients should be observed for infusion-related adverse events for at least 1h after the loading dose and if there are no ill effects, for 15min after maintenance doses. The most common side effects are diarrhea, dizziness, nausea and rash.
There are no anticipated drug interactions. Renal insufficiency is not expected to affect ibalizumab's pharmacokinetics. Resistance to other antiretroviral agents does not seem to affect ibalizumab's activity .Safety data are insufficient for this drug to be used in pregnancy or in pediatric patients. The anticipated annual wholesale acquisition cost of ibalizumab is $118,000).
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- Shirakawa K, Chavez L, Hakre S, Calvanese V, Verdin E (2013) Reactivation of latent HIV by histone deacetylase inhibitors. Trends Microbiol 21: 277-285.
- Vorinostat (2020) Available online at: https://en.wikipedia.org/wiki/Vorinostat
- Mediouni S, Jablonski J, Paris JJ, Clementz MA, Thenin-Houssier S, et al. (2015) Didehydro-cortistatin A inhibits HIV-1 Tat mediated neuroinflammation and prevents potentiation of cocaine reward in Tat transgenic mice. Curr HIV Res 13: 64-79.
- Pebody R (2020) Top 5 HIV cure and vaccine stories from AIDS 2020. HIV & AIDS. Available online at: https://www.aidsmap.com/news/jul-2020/top-5-hiv-cure-and-vaccine-stories-aids-2020
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