HIV replication during ART remains unproven, challenging previous study

Findings recently published in Open Forum Infectious Diseases indicated that HIV replication did not occur in lymph nodes after patients began ART, disputing the results of a 2016 study.

“In their report, Lorenzo-Redondo et al. performed deep sequencing on 454 bulk polymerase chain reaction-amplified samples from blood and [lymph nodes] collected 3 and 6 months after initiating ART in three individuals and compared them with [peripheral blood mononuclear cells] and plasma sequences obtained from before ART,” Mary F. Kearney, PhD, of the HIV Replication and Dynamics Program at the National Cancer Institute, and colleagues wrote. “They concluded that ongoing HIV replication occurs in the lymph nodes during ART and that this replication maintains the HIV reservoir.”

Kearney and colleagues carried out an analysis of the same sequences included in the original study, reviewing HIV RNA and proviral DNA sequences that occurred in lymph nodes and peripheral blood mononuclear cells from three patients with HIV who were receiving ART.

The researchers reported that after they accounted for polymerase chain reaction resampling and hypermutation, “the dataset was very limited,” yielding a median of five unique RNA or DNA sequences per sample.

After 6 months, the researchers wrote, the remaining DNA sequences were no more diverse than those found before patients initiated ART, nor were they divergent from the original sequences.

“These results show that, rather than an increase of viral diversity on ART from the pretherapy population, a loss of genetic diversity, including narrowing of the proviral populations toward identical sequences, is observed,” the researchers wrote. “In summary, from our re-analysis of the sequences published by Lorenzo-Redondo et al., combined with evidence from prior studies and current analyses of samples whose dominant proviruses are known to arise from cellular proliferation rather than viral replication, we find that conclusions in the publication by Lorenzo-Redondo et al. are not valid and that the concept of ongoing HIV replication during ART remains unproven.” – by Andy Polhamus

Disclosures: Kearney reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

References:

Lorenzo-Redondo R, et al. Nature. 2016;doi:10.1038/nature16933.