Is it expected to eradicate HIV infection? Gilead combination therapy demonstrates effectiveness March 06, 2018 Source: WuXi PharmaTech Recently, Gilead Sciences announced that its preclinical studies in collaboration with the Beth Israel Deaconess Medical Center have demonstrated that the combination of GS-9620 and PGT121 can stop rhesus monkeys infected with marmoset-human immunodeficiency virus (SHIV). After viral therapy (ART), viral suppression can still be maintained. The data, published at the 2018 Conference on Retroviruses and Opportunistic Infections (CROI), supports further research into a combination of strategies involving these two classes of drugs to explore the potential for long-term viral suppression without the need for daily ART. . Human immunodeficiency virus (HIV) attacks the body's immune system, especially T lymphocytes. If left untreated, HIV reduces the number of T cells in the body, leading to a decline in the body's ability to fight infections and other diseases. Although ART can effectively control HIV and prolong the life span of AIDS patients, so far, there is still no way to completely eliminate HIV, thus completely curing AIDS. There is still huge medical needs in this area to be met. The GS-9620 and PGT121 involved in this study are Gilead's proprietary oral Toll-like receptor 7 (TLR7) agonists and broad-spectrum neutralizing antibodies (bNAb) PGT121, respectively, as part of the HIV eradication strategy. Evaluation is performed in preclinical studies. In this study, 44 rhesus monkeys infected with SHIV started ART on the 7th day after infection. After 96 consecutive weeks of ART treatment, the animals were divided into four groups, each receiving 5 doses of PGT121 (10 mg/kg per week for 10 weeks) (n=11), 10 doses of GS-9620 (every two Weekly perfusion of 0.15 mg/kg for 20 weeks) (n=11), combination of PGT121 and GS-9620 (n=11), or no placebo treatment (n=11). Animals continued to receive ART during this period and 16 weeks afterwards. ART stopped at week 130 and monitored viral rebound in plasma. After ART stopped, 11 animals in the placebo group showed a viral rebound with a median rebound time of 21 days; 9 animals receiving PGT121 showed a viral rebound; 10 animals receiving GS-9620 showed a viral rebound. In contrast, 5 animals treated with the combination of PGT121 and GS-9620 did not show a viral rebound for at least 168 days; the other 6 animals in the combination therapy rebounded, but then again without ART Virus suppression has occurred. ▲ Dr. Dan H. Barouch, Professor of Harvard Medical School (Source: Harvard Medical School) "HIV is hidden in certain immune cells. This cell is called the latent virus library, which is a key barrier to HIV. New HIV treatments aim to awaken and target these virus banks, possibly in long-term viruses without ART. "Inhibition plays an important role," said Dr. Dan H. Barouch, a professor at Harvard Medical School and director of the Center for Virus and Vaccine Research at Beth Israel Deaconess Medical Center. "In this pre-clinical study of proof-of-concept, 45% received GS-9620 and PGT121. Animals did not show a viral rebound after stopping ART, suggesting that this combination therapy may target the viral pool in monkeys that are suppressed by the virus." “We are still committed to researching and developing HIV eradication strategies. These are encouraging data from CROI's preclinical data from animal models of HIV infection. They suggest that GS-9620 and PGT121 combinations may induce viral remission without ART. Dr. Norbert W. Bishofberger, Executive Vice President and Chief Scientific Officer of Gilead R&D, said: "GS-9620 is currently being evaluated in the Phase 1b dose escalation study of HIV-inhibited HIV-infected individuals. We have already introduced PGT121 derivative GS-9722. Advance to the Phase 1 trial phase." We wish the follow-up clinical trials to go well and look forward to the end of humanity in the near future. Reference materials: [1] Gilead's Preclinical Combo Trial Might Eradicate HIV [2] Gilead Announces Data from New Preclinical Study Evaluating a Combination of an Investigational TLR7 Agonist and an Investigational HIV Envelope Targeting Antibody in SHIV-Infected, Virally Suppressed Monkeys Insulin Syringes Needle,Disable Syringe,Monoject Syringe,10 Ml Syringe FOSHAN PHARMA CO., LTD. , https://www.fospharma.com
