In a critical step that may lead to more effective HIV treatments, Harvard scientists have found pre-existing mutations in a small number of HIV patients. These mutations can cause the virus to develop resistance to the drugs used to slow its progression.
The finding is particularly important because, while researchers have long known HIV can develop resistance to some drugs, it was not understood whether the virus relied on pre-existing mutations to develop resistance, or if it waits for those mutations to occur. By shedding new light on how resistance evolves, the study, reported in online journal PLoS Computational Biology opens the door to the development of new, more effective treatments.
Pennings collected her data from 26 clinical trials. Patients were treated with a typical combination of NNRTI drugs, which helps block the virus from multiplying. She found that the virus is more likely to develop resistance shortly after the start of treatment or when treatment is restarted following an interruption of a week or more. However, it is less likely to develop resistance later on and when patients do not interrupt treatment.
"In order to prevent the evolution of resistance, we need to know where the resistance mutations are coming from, it was exciting to realize data from clinical trials could help us solve this puzzle," Pennings said. "If we understand how the virus develops resistance, we can think of new ways to prevent it."
This finding suggests that pre-existing mutations are behind the virus' drug resistance, and that resistance which develops early in treatment is likely the result of pre-existing mutations. Resistance that develops later is tied to mutations in the virus that occur after treatment began.
While the study holds out hope for the future development of more effective HIV treatments, Pennings emphasized that data used in the study came from trials, which exclusively included patients receiving NNRTI or unboosted protease inhibitor treatments. It is unclear whether the results can be generalized to other treatments and to patients who are not enrolled in clinical trials.