Researchers at the Rockefeller University and at the U.S. Centers for Disease Control and Prevention (CDC) have tested a reformulated HIV drug that offers long-lasting protection against infection from the virus that causes AIDS. The drug, GSK744, developed by the British pharmaceutical giant GalaxoSmithKline, is a version of dolutegravir (Tivicay), an HIV drug already on the market.
The tests were performed using macaque monkeys, and found to protect the monkeys from repeated exposure to a monkey/human version of the virus (called SHIV, for “simian human immunodeficiency virus”) under conditions designed to replicate sexual transmission. In the study conducted at the CDC, researchers injected GSK744 monthly into six female monkeys, then exposed them twice weekly to SHIV intra-vaginally. None of the treated monkeys became ill, but the negative control group – six monkeys who received a placebo – all became infected. The researchers at the Rockefeller tested GSK744 on 15 monkeys by exposing them to the SHIV virus through anal injection. Here again, none of the animals receiving the experimental drug were infected, but all in the placebo group were infected.
The animal studies suggest that a single administration of the drug can offer protection from infection for up to three months. Results in animal trials do not always translate directly into human therapies, however, so clinical trials will be necessary. A first clinical trial with 175 people is expected to begin later this year in the United States, Brazil, South Africa and Malawi.
GSK744 is what’s known as an “integrase inhibitor” – a drug that works by preventing HIV from integrating its genetic material into the cells it infects. The drug has been modified so that it crystallizes in the blood-stream, releasing slowly over time to produce its long-lasting protection against HIV infection.
One of the most difficult-to-manage aspects of treatment for HIV infection currently is lack of adherence – that is, when patients are unable or unwilling to take their mediations as prescribed. At this time, patients who are dependent on a pharmacological regimen to stay healthy are required to take their meds on a daily basis. Non-compliance comes at a cost – if the drugs are not taken every day, the potential exists for the virus to evolve into a drug-resistant strain, posing a threat to the patient, as well as a public health concern. Also, partners of HIV-positive people can take small doses of anti-retrovirals daily to reduce their risk of infection by 90 percent. If the prophylactics are not taken on a daily basis, however, the protection is considerably diminished. A drug that protects for three months can be taken on a quarterly basis, considerably diminishing the risk of non-adherence.
Despite the development of Highly Aggressive Anti-Retroviral Therapy (HAART treatment – the so-called “drug-cocktail”) in 1995, that turned HIV from a fatal disease into a manageable chronic infection, the search for a cure for the virus has been elusive. Over the last 30 years, HIV has been extensively studied; numerous therapeutics have been developed and found effective for keeping viral numbers low in infected patients. Despite this, HIV infections continue. According to the researchers who performed the GSK744 study, 2.3 million new infections occurred around the world in 2012; 35.5 million people are already living with HIV.
An HIV drug that protects against infection on a long-lasting basis will considerably simplify the process of treating persons infected with HIV. The Rockefeller and CDC virologists presented their findings yesterday in Boston at the Conference on Retroviruses and Opportunistic Infections. Their results are also published online in the March 6 issue of the journal “Science.”
By Laura Prendergast