HIV Replicates, Mutates in the Brain Soon After Infection

The brain can harbor active HIV even after seemingly successful antiretroviral treatment.

The long-term effects of HIV and the AIDS virus on the brain are well-known, but researchers recently uncovered that the virus replicates in the brain much earlier than thought.

For some patients, HIV can start replicating in the brain as early as the first four months of infection, according to researchers behind the NIH-funded study. Cerebrospinal fluid in 30% of HIV-infected patients showed at least transient signs of inflammation or viral replication within the first two years of infection.

“These results underscore the importance of early diagnosis and treatment with antiretroviral therapy,” said Dianne Rausch, PhD, director of the Division of AIDS Research of the NIH’s National Institute of Mental Health (NIMH), in a press release. “Any delay runs the risk that the virus could find refuge and cause damage in the brain, where some medications are less effective – potentially enabling it to re-emerge, even after it is suppressed in the periphery.”

The study, published in PLoS Pathogens, also aimed to identify if the brain serves as a hideout from which the virus can re-infect the body even after elimination from peripheral blood and lymph node tissue.

Researchers compared the HIV activity in cerebrospinal fluid to blood from 72 untreated HIV-infected patients during the first two years of infection. Ten to twenty-two percent of the patients had evidence of HIV replication or inflammation in the brain over the course of two years, some of which persisted over time in 16% of patients. The findings suggest that peripheral forms of the virus infect immune cells that spread to the brain through blood. However, genetic versions of the virus that are not found in blood also evolve in the brain environment in some patients, suggesting that the brain can harbor the virus and may be capable of generating treatment-resistant mutations that could re-infect the body.

Whether or not antiretroviral treatment can reverse the brain damage that accompanies HIV replication and inflammation is still unknown. 


  1. Sturdevant CB, et al. PLoS Pathog. 2015; doi:10.1371/journal.ppat.1004720.