The first factor is compression of the navicular bone under the DDF tendon and the back of the small pastern bone. Repeated compression in this area can cause cartilage degeneration, with the cartilage flattening and gradually becoming less springy and shock-absorbing. It may also begin to erode. Cartilage degeneration is common in navicular horses, usually along the flexor surface. This finding, and the associated biochemical changes, have led some researchers to conclude that there are elements in navicular disease common to osteoarthritis, and to suggest similar therapeutic regimes.Cartilage erosion may progress to the point that the bone underneath will become exposed. With the cartilage no longer present to protect it, the navicular bursa and DDF tendon may become damaged by the constant rubbing against the navicular bone. Navicular bursitis (inflammation of the navicular bursa) may occur, even if cartilage damage is not severe. This is probably due to the friction between the navicular bone and the DDF tendon from compression. Constant compression can also increase the bone density directly under the cartilage surfaces, especially on the flexor side. This tends to make the bone more brittle, and thus more likely to break. Another main factor is the tension placed on the ligaments that support the navicular bone. Some experts believe that the degenerative process begins with excess tension placed on these ligaments, causing strain and inflammation.
Most participants had been treated for HIV for more than 15 years (71 percent), had been exposed to five or more different HIV treatment regimens before entering the trial (85 percent) and/or had a history of AIDS (86 percent). Participants in the main cohort of the trial received either fostemsavir or a placebo twice daily for eight days, in addition to their failing antiretroviral regimen. On the eighth day, participants treated with fostemsavir had a significantly greater decrease in levels of HIV-RNA in their blood compared to those taking the placebo. After the eighth day, all participants received fostemsavir with other antiretroviral drugs. After 24 weeks of fostemsavir plus other antiretroviral drugs, 53 percent of participants achieved HIV RNA suppression, where levels of HIV were low enough to be considered undetectable. After 96 weeks, 60 percent of participants continued to have HIV RNA suppression.The clinical trial (NCT02362503) was conducted at 108 sites in 23 countries in North America, South America, Europe, Australia, Taiwan and South Africa.The U.S. Food and Drug Administration (FDA) granted the application for fostemsavir fast track, priority review, and breakthrough therapy designations. The FDA granted the approval of Rukobia to ViiV Healthcare.On 10 December 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Rukobia, intended for the treatment of multi-drug resistant HIV-1 infection.