Progress in HIV Research in October 2018 (I)

Human immunodeficiency virus (HIV), an AIDS (AIDS, acquired immunodeficiency syndrome) virus, is a virus that causes defects in the human immune system. In 1983, HIV was first discovered in the United States. It is a lentivirus that infects cells of the human immune system and is a type of retrovirus. By destroying the body’s T lymphocytes, HIV blocks cellular and humoral immune processes, causing the immune system to deficiency, and causing various diseases to spread in the human body and eventually leading to AIDS. Due to the extremely rapid variation of HIV, it is difficult to produce a specific vaccine, and there is no effective treatment method to date, which poses a great threat to human health.


Since the 1980s, the AIDS epidemic has claimed more than 34 million lives. According to the World Health Organization (WHO), it is estimated that in 2017, 36.9 million people worldwide were infected with HIV, and only 59% of HIV-infected people were treated with antiretroviral therapy (ART). To date, HIV remains one of the world’s largest public health challenges, so there is an urgent need to delve into the function of HIV to help researchers develop new therapies that can effectively fight the disease. In order to prevent the virus from causing damage to the immune system, HIV-infected people need to take ART every day or even for life. Although taking ART has been shown to be effective in suppressing AIDS episodes, these drugs are expensive, time-consuming, and have serious side effects. There is an urgent need to find ways to cure HIV infection.


  • Nature: Significant progress! Use a combination of TLR7 agonists and extensive neutralizing antibodies could kill latent HIV virus libraries




In a new study, Barouch and colleagues demonstrated that the combination of a broadly neutralizing antibody (bNAb) targeting HIV and a Toll-like receptor 7 (TLR7) agonist that stimulates the innate immune system can delay HIV rebound in monkeys stop taking ART drugs. These findings suggest that this two-pronged approach represents a potential strategy for targeting this virus pool. The results of the study were published online in the journal Nature, entitled “Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys”.


Barouch and colleagues studied 44 rhesus monkeys infected with HIV-like virus (SHIV) and started treatment with ART for two and a half years after infection. After 96 weeks, these rhesus monkeys were divided into four groups. One group, the control group, did not receive any further study treatment. The other two groups were given only TLR7 agonists or only bNAb antibodies. The fourth group was given both a TLR7 agonist and bNAb antibody. All rhesus monkeys continued to receive ART medication until the 130th week of stopping the treatment, at which time the researchers began monitoring whether the rhesus monkeys showed signs of a rebound in SHIV.


As expected, in the control group, all rhesus monkeys rapidly rebounded with SHIV and they had a relatively high viral load peak, while in rhesus monkeys that only gave this TLR7 agonist, almost the same with the control group. However, of the rhesus monkeys receiving this combination therapy, 5 of the 11 rhesus monkeys did not rebound from SHIV within 6 months. In addition, another 6 rhesus monkeys with SHIV virus rebound showed lower viral load peaks than rhesus monkeys in the control group. Rhesus monkeys given only bNAb antibodies showed a detectable rebound in SHIV virus, although this virus rebound was delayed.


  • Science Supplement: There is a hope to cure HIV infection! Anti-α4β7 therapy weakens lymphocyte recruitment in the gastrointestinal tract of HIV-infected patients




In a new study, researchers from research institutions such as Icahn Medical School in Mount Sinai, USA, for the first time described a mechanism that could lead to a reduction in immune cell populations called lymphoid aggregates in the gastrointestinal tract. Among them, lymphocyte gathering is an important refuge for maintaining the HIV virus library. Given that the gut plays an important role in HIV infection, these findings may be of interest to scientists involved in research to cure HIV infection. The results of the study were published in the issue of Science Translational Medicine, entitled “Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1–infected individuals”. The author of the paper is Dr. Saurabh Mehandru, Associate Professor of Medicine (Gastroenterology) at Ikan School of Medicine, Mount Sinai.


The researchers designed a treatment experiment involving 6 people with mild inflammatory bowel disease (IBD) who were infected with HIV-1 to receive anti-α4β7 drugs—especially vedolizumab (VDZ). VDZ has become the first line of drugs to control the condition of patients with IBD, in which it shows strong efficacy and excellent safety. They studied immune cells in the blood and intestines and described the immunological and virological effects of VDZ treatment within 30 weeks.


  • Nat Commun: New long-acting injections are expected to prevent and treat HIV infection





An ongoing challenge for HIV treatment and prevention is the need to adhere to medication, which allows patients to take the medication as required to get the best treatment. Nowadays, tablets taken to prevent HIV infection are available every day, but for some patients, it may be very difficult to stick to the strategy of taking medicine every day. Recently, a research report published in the international magazine Nature Communications, scientists from the University of North Carolina and the US CDC reported a potential strategy to solve the above problems.


In the article, the researchers developed a long-acting, injectable and mobile antiretroviral drug formula, dolutegravir, which has been tested in animal models for the treatment effect. This injectable therapy includes anti-HIV drugs, polymers, and solvents; liquids containing three components will solidify into an implantable substance once injected into the skin, releasing the drug when the polymer slowly degrades.


Researcher Dr. Martina Kovarova said that we found that this formula is effective in transporting drugs and that this implantable substance is well tolerated, has almost no toxic effects, and can last for five months. This new treatment seems to be an ideal drug therapy for the prevention and treatment of AIDS. In addition, the researchers have found that the implant can be quickly and safely removed by forming a small incision in the skin of the implantation site.


  • How to test tuberculosis for HIV carriers?

News source: Scientists develop rapid test for diagnosing tuberculosis in people with HIV


International teams, including Rutgers University scientists, have made significant advances in the development of urine diagnostic tests that can identify tuberculosis infections in HIV-infected populations quickly, easily and at low cost. Tuberculosis is the world’s leading infectious disease killer and the most common cause of death among people living with HIV, and early diagnosis and treatment can prevent most tuberculosis deaths. The findings were announced at the UN Tuberculosis Conference on September 26, 2018.


“TB is a major health problem in poor areas of the world,” the authors said. “Therefore, in addition to being effective, the test must be inexpensive, easy to use and explain, or even independent of the instrument or electricity. In addition, the results need to be obtained quickly before the patient leaves the clinic so that they can start medication as soon as possible, thereby reducing the spread opportunities for infection.” In this new study, scientists and clinicians from Rutgers, FIND and other institutions have shown that new assays are much more sensitive than existing assays. A key component of the new trial is the author’s novel monoclonal antibody isolated from infected patients, which strongly recognizes the presence of LAM in urine. Data from several other recent publications from this key antibody suggest that these tests may also be sensitive to patients without HIV infection. “By doing this test in more patients, we want to prove its effectiveness in identifying new infections and hope to reduce mortality,” he said. “If the results are positive, this could become a widely used point-of-care test to help stop the tuberculosis epidemic.”


(To be continued…)


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