Solving the Puzzle of Persistent HIV Replication

Research explores how HIV is able to evolve during antiretroviral therapy.

A new study found that ongoing HIV replication in lymphoid tissues helps maintain reservoirs of the virus in patients undergoing antiretroviral therapy (ART).

Scientists have debated if viral reservoirs in tissues are maintained due to persistent infected cells or low level HIV replication, or even for both reasons.

The study, performed by researchers at Northwestern Universit, took 3 HIV patients to sequence viral DNA from collected lymph node and blood cells.

Prior studies indicated that antiretroviral drug concentrations were lower in lymphoid tissue than in the blood, which means that HIV could hide in sanctuaries that drugs could not easily penetrate.

The results of the current study showed that the virus evolved over time, which suggests ongoing replication, but didn’t accumulate mutations that were drug resistant. Researchers were able to show that continued HIV replication in lymphoid tissue sanctuaries refills viral reservoirs in ART patients that had undetectable HIV levels in the blood levels.

Researchers also used a mathematical model in order to try and explain how the virus was able to evolve during ART without emerging as highly drug-resistant strains.

The drug sensitive HIV strains would dominate over the drug resistant strains when the medication concentration was low. The resistant strains were able to start dominating at intermediate drug concentrations, while HIV could not grow at high drug concentration levels.

According to the authors of the study, in order to get a full understanding of how viral reservoirs are maintained, further studies need to be performed using drugs that are better able to penetrate the entire lymphoid tissue compartment.