HIV transcription remains active in brains of some virally suppressed people with HIV

HIV continues to actively transcribe in the brain of people living with HIV even if they are virally suppressed, according to recently published research. This finding may help explain the development of neurocognitive issues and has implications for cure research, the study authors contend.

About This Study

“HIV transcription persists in the brain of virally suppressed people with HIV” was published online on Aug. 8, 2024, in PLoS Pathogens. The lead author is Janna Jamal Eddine, a Ph.D. candidate within the School of Health and Biomedical Sciences at RMIT University in Melbourne, Australia.

Key Research Findings

During autopsy, researchers in Australia investigated HIV transcription in the brain tissue (frontal cortex) of 24 people who had been living with HIV, 11 of whom had been virally suppressed for at least two years prior to death. The median age at death was 59 years for virally suppressed participants and 46 years for participants with viremia.

At autopsy, most viremic participants had viral loads in the five- to six-digit range, as high as 750,000 copies/mL. In that group, CD4 count was as low as 1 cell/mm³, with a median 8 cells/mm³. In virally suppressed participants, the median count was higher, but still low: 274 cells/mm³.

Almost all samples had some HIV transcripts, with similar levels of trans-activation response (TAR) transcripts regardless of viral suppression. The tissue from two virally suppressed and seven non-suppressed participants contained all transcript species. Transcription was completed in 12 of the 13 participants with viremia, compared to five of the 11 virally suppressed participants. Samples from the suppressed group included a block to completing transcription that was not in samples from the viremic group.

Discussion Highlights and Implications for Practice

Study limitations reported by the authors included the single timepoint represented by autopsied tissue and a lack of information on whether the transcripts were generated by replication-competent virus.

The researchers concluded that the results show that HIV remains active in the brain even in virally suppressed people living with HIV. They believe that such activity may be related to the development of neurocognitive disorders despite successful antiretroviral treatment.

Research into antiretroviral regimens that penetrate deeper into the central nervous system is needed to stop viral activity in the brain, the authors stated. Investigating latency reversing agents in HIV cure research would similarly need to get into the brain and overcome the blocks observed in this study, they said.

By Barbara Jungwirth