Advances in antiretroviral therapy have prolonged the lives of many patients with human immunodeficiency virus, transforming the disease from fatal to chronic. But a sizeable number of HIV patients are developing or acquiring highly drug-resistant HIV. HIV has proven to be a masterful adversary, quickly mutating and replicating, leaving the benefits of many medications void.
But a study led by Roy T. Steigbigel, M.D. – a professor of Medicine, Pathology, Microbiology and Pharmacological Sciences at Stony Brook University Medical Center — and colleagues worldwide found that raltegravir, a new medication to treat HIV infection, combined with other anti-HIV medications, demonstrated superior suppression of HIV-1 in patients with highly resistant virus compared with placebos.
“This is important because people who have been infected with HIV for a fair amount of time have no control anymore of their bodies and they can get very sick and die…[raltegravir] allows patients to get some control for a period of time,” Steigbigel said.
Raltegravir, also known as Isentress, is a type of medicine called an integrase inhibitor. Integrase is a protein that HIV needs to insert its viral genetic material into the infected cell, and the inhibitors work by blocking the integrase.
In most patients with highly drug-resistant HIV, the resistance develops from sequential exposure to HIV drug. The current HIV regimen in use is designed to suppress the virus, and the emergence of drug-resistant mutations. But the genetic barrier to drug resistance for several of the most important HIV agents is low, requiring only a single point mutation. This drug resistant virus can also be transmitted from person to person and from mother to child. “People who are newly infected can get infected by drug resistant HIV,” Steigbigel said.
Featured in the July 24 edition of the New England Journal of Medicine, patients who received raltegravir had higher rate of virologic suppression than those who received the placebo, and the overall suppression rates of viral suppression are among the highest reported for patients infected with highly resistant HIV. “The breakthrough is that the drug acts on new targets,” Steigbigel said. Targets are the part of the virus where it replicates itself, resulting in higher chances of replications.
Steigbigel’s study evaluated the activity of raltegravir among 699 patients infected with HIV. Only patients with severely drug resistant HIV, or those documented with three classes of HIV drugs, were eligible for the study. According to the study, virologic response rates were 51, 61 and 71 percent when raltegravir was provided in combination with no, one, or two other active drugs. Resistance to raltegravir requires only a single point of mutation, and among the 94 subjects in the study with virologic failure, about two thirds showed resistance by week 48. In order for the drug to work effectively, Steigbigel emphasized that its “adherent for people to take the medication regularly.” Irregular use of the medication can quickly result in resistant strains of HIV, working as quickly as “months.”
Steigbigel also said that the combination therapy with the drug helped the immune system to rebound in some patients as CD4 counts were more pronounced in the raltegravir group as compared to the placebo group.
Since 2003, nine new drugs and three new drug classes, including HIV integrase inhibitors, were approved for HIV treatment. Raltegravir was the first compound of this class to be approved for clinical use on October 12, 2007 by the FDA. Raltegravir does not cure or prevent HIV infection or AIDS and does not reduce the risk of passing the virus to other people.
