At Last, Hope for Individuals with HIV
HIV-1 infected individuals are treated with lifelong antiretroviral drugs to control the infection. A means to strengthen the antiviral T cell response might allow them to control viral loads without antiretroviral drugs. The results support the development of this approach as a therapeutic vaccine that might allow HIV-1 infected individuals.
Scientists believe a cure for AIDs could be in sight, following the successful treatment of a man in London that has made him HIV-free for 18 months. He is the second person to have a bone marrow transplant to successfully rid them of HIV. Current antiretroviral treatment makes living with the virus much more manageable to when doctors first began trying to treat HIV/AIDs both of the patients also had a form of cancer. In both cases, both donors were found a mutation in the CCR5 gene that gives the patient resistance to the HIV virus. A deletion in the CCR5 gene stops receptors from functioning properly (Warren, 2019).
Treatments available so far
The need for multiple doses of antiretroviral treatment has been associated with worse adherence resulting in impaired suppression in treating HIV. Adherence difficulties have led to studies to explore treatment simplification. Once a day dosing was much better adhered to than the current three to four times a day. This, in turn, has led to an improved quality of life for these individuals. Based on a cohort of 3212 patients the study compared the effectiveness and tolerance of single tablet regimes and non-single tablet regimes in real life conditions. Even the French National Healthcare Insurance database showed that persistence in treatment was higher in single tablet regimes when compared to other administration schedules. One limitation noted of the study were those HIV⁺ patients with comorbid conditions. This would cause some people to be unable to use the medications used in single tablet regime. But it does show patients who can receive single tablet regimes have much higher compliance and better virological efficacy. Further study is needed and warranted (Cotte et al, 2019).
As soon as the primary infection of HIV occurs, a pool of infected cells carrying transcriptional proviral DNA referred to as the HIV-1 reservoir. Antiviral medications do not clear these cells and they persist life-long in treated individuals. Current treatment of HIV infection, the combined antiretroviral of several viral enzymes needed to block HIV replication. However, when treatment is interrupted the HIV spontaneously reoccurs. Current studies are focusing on eradication of the pool of latently infected cells in HIV-infected individuals has been approached from molecular, pharmacological and immune perspectives. While the medications used today help keep the multiplication HIV virus, the pool of latently infected cells is not static. Antibodies show a wide range of antiviral activities that make them highly attractive as anti-HIV-1 agents. The clinical setting for antibody treatment is also an open field. Newly designed antibodies show a potency equivalent to the most active antiretroviral and a wide range of immunological effect, most of them not completely understood. And further trials and studies need to be done (Carrillo, Bonaventura, & Blanco, 2018).
Despite the success of antiretroviral therapy HIV-1 is managed as a chronic disease due to its persistence in the long-lived population of resting memory CD4⁺ T cells. This latent reservoir of HIV-1 in antiretroviral treatment suppressed individuals in considered a critical barrier to a cure. Lack of viral protein expression in latently infected cells allows the reservoir to escape immune surveillance. Studies are currently being done called the “Kick and Kill” approach to controlling HIV-1involves inducing latency reversal during antiretroviral treatment to expose infected cells. At the same time creating an arsenal of immune effector cells. Finding an effective means to expose and purge the latent reservoir in a nontoxic manner. This study while making great studies still has not found the exact method to signaling pathway to contribute to noted latency reversal. The investigators noted a few shortcomings with their study. Researchers did not observe influenza antigen-mediated latency reversal. In addition, the study did not truly identify the antigen specificity of infected CD4⁺ T cells. Nonetheless, the results provide a strong rationale for further study (Kristoff et al, 2019).
New strides bring hope
Bone marrow is known to be a unique organ for immunological memory including memory T cells. Blood cancers require a bone marrow transplant to replace the bone marrow that had been destroyed with chemotherapy. A large number of trials have been conducted to explore the potential of various agents. T cells are able to access a molecular pharmacy to create large numbers of powerful immune cells. Chemokine CCR5 controls macrophage migration and T cell interaction. This is currently being investigated for treatment against MS, RA, asthma, nephritis, IBD, HIV, transplant rejection, and graft versus host tissue. T cell positioning in relation to antigen and inflammatory cues in secondary lymphoid organ is key in determining T-cell phenotype. Immune memory at first observed by Thucydides is defined as the ability of the immune system to respond more effectively when exposed to a second encounter with the disease. This is the way vaccines work in the human body to afford resistance/cure from the disease within the human body (Khan, 2019).
University of Pittsburgh Graduate School of Public Health scientists has reported that they have developed an all-in-one immunotherapy approach that not only kicks the HIV out of its hiding places in the immune system but also kills it. The key they found is in immune cells designed to recognize an entirely different virus. This discovery is yet to be tested in clinical trials but scientists are confident this breakthrough could lead to the development of a vaccine to help those positive for HIV to stop taking daily antiviral medication. By making use of MDC1 cells to T cells containing latent HIV, they reversed that latency and proceeded to eliminate virally infected cells (University of Pittsburgh, 2019).
Recent data has found the treatment for acute leukemia may have an effect on latent HIV-1 reservoirs. This has opened the possibility that the drug re-enters into the context of HIV-1 eradication strategies. According to an article reported in The New York Times, dated March 4, 2019, it appears a second man has been cured of his HIV status. In 1995 a man from Washington State had contracted HIV. After 11 years of taking antiretroviral medicines, he developed acute myeloid leukemia. He was living in Berlin Germany at the time and he was given chemotherapy at first but that didn’t work. After that, he was given two different bone marrow transplants. When the second one was done he stopped taking his antiretroviral medicine and unlike the usual response, doctors could not find any viral material able to replicate. Upon looking at the patient who had donated the bone marrow it was found that he had a mutation in his CCR5 T-cell genes. Now, this miracle of medicine has been replicated as reported in this year of 2019. A man who had HIV had also been diagnosed with non-Hodgkin’s lymphoma. He was in London England at the time and was treated with a bone marrow transplant that also contained a mutation in the CCR5 T-cell genes. Eighteen months later and man is still testing free of HIV. And while the scientists are not ready to call the two different cases where the men have been made free from HIV a cure, it does provide hope that being diagnosed with HIV is not the death sentence it once was (Mandivilli, Mar. 4, 2019).
Carrillo, J., Bonaventura, C. & Blanco, J. (2018). Antibodies and antibody derivatives: New partners in HIV eradication strategies. Frontiers in Immunology, 9(2429).
Cotte, L. et al. (2017). Effectiveness and tolerance of single tablet versus once daily multiple tablet regimes as first-line antiretroviral therapy-results from a large French multicenter cohort study. PLoS ONE, 12(2).
Khan, A.B. (2019). Targeting therapeutic T cells to the bone marrow niche. Doctoral Thesis (Ph.d). University College in London.
Kristoff, J. et al. (2019). Type-1 programmed dendritic cells drive antigen-specific latency reversal and immune elimination of persistent HIV-1. EBioMedicine.
Mandivilli, A. (March 4, 2019). HIV is Reported Cured in a Second Patient, a Milestone in Global AIDs Epidemic. The New York Times-Health. The New York Times Company.
Norton, T.D. et al. (2019). Lentiviral vector-based dendritic cell vaccine suppresses HIV replication in humanized mice. Cell Press.
The University of Pittsburgh. (2019). Immunotherapy ‘Kicks and Kills’ HIV by exploiting a common virus. University of Pittsburgh Graduate School of Public Health.
Warren, M. (2019). Second patient free of HIV after stem cell therapy. Nature International Journal of Science.