Lately, two Phase III clinical trials of a combination treatment of two drugs that inhibit different parts of the HIV virus have exhibited heartening results. When given as an intramuscular injection, the therapy was as effective as pills and persisted in the body for at least a month.
HIV diagnosis is no more a death sentence and now people taking treatment survive for decades with the disease. Keeping the virus at bay usually requires taking a pill every day, which aside from being inconvenient for some, is an unwelcome daily reminder of the disease. That’s why drug companies are developing longer-acting, injectable HIV treatments.
At CROI, ViiV Healthcare released Phase III data from two trials of an injectable treatment consisting of cabotegravir and rilpivirine. Cabotegravir is a new molecule that blocks the HIV integrase enzyme, a protein critical in helping HIV insert its genome into the DNA of the T cell it infects (J. Med. Chem. 2013, DOI: 10.1021/jm400645w). Rilpivirine, already approved as a pill, is part of an older class of drugs called nonnucleoside reverse transcriptase inhibitors. It’s a small molecule that binds to and blocks HIV’s reverse transcriptase, the enzyme that allows the virus to copy its genetic material and replicate (Virus Res. 2008, DOI: 10.1016/j.virusres.2008.01.002. The two, when packaged together for intramuscular injection, can last in the body for 1 month or longer.
According to the U.S. Centers for Disease Control and Prevention, 38,000 people in the U.S. were newly infected with HIV in 2017. For more than 15 years, the first line of therapy has been a suite of antiretroviral drugs in pill form, taken once a day. Although this treatment has transformed HIV from a certain killer to chronic disease in much of the developed world, there are problems. For example, some people have trouble taking their pill every day. Therefore, pharmaceutical companies are developing injectable HIV drugs that target different components of the virus and can be administered once every few weeks, writes Senior Editor Megha Satyanarayana.
Currently, at least nine long-acting injectable therapies for HIV are in clinical development. Recently, ViiV Healthcare released data from two Phase III clinical trials of a combination treatment of two drugs ¬that inhibit different parts of the virus. When given as an intramuscular injection, the therapy was as effective as pills and persisted in the body for at least a month. In addition, more than 97% of study participants said in a survey that they preferred the long-acting injectable to daily pills. Other researchers are looking beyond treatment to a possible cure for HIV, developing therapies, such as broadly neutralizing antibodies, that could “wake up” and then kill dormant viruses. Although injectable HIV drugs could be a welcome convenience for many, some experts are skeptical that they would actually improve treatment compliance, especially among people who are homeless or lack stable insurance coverage.