Researchers have identified a long-lived reservoir of infectious HIV-1 in clonally expanded CD4+ T-cells found in a patient with persistent viremia, even after years of combination antiretroviral therapy.
The existence, persistence, and expansion of clonal HIV-1 cells in antiretroviral-treated patients has been demonstrated previously, but it was not known whether these cells could contain replication-competent provirus.
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The case study, published online February 8 in PNAS Early Edition, reported on a 58-year-old man first diagnosed with HIV-1 infection in 2000, who experienced an increase in viral load 12 years after starting combined antiretroviral therapy.
“SGS [single genome sequencing] of the viral RNA in plasma revealed two distinct populations: a genetically diverse group of drug-resistant viruses and a second population of identical viruses that lacked drug resistance mutations,” wrote Dr. Frank Maldarelli of the HIV Dynamics and Replication Program at the National Cancer Institute, and his coauthors.
While the authors suggested only a fraction of the clonal cells were producing HIV at any given time, the clones were able to persist and clonally expand to around nine million cells (PNAS Early Edition. 2015 Feb 8. doi: 10.1073/pnas.1522675113).
“The data presented here demonstrate that clonally expanded cells containing an intact, infectious provirus can persist and produce virus for many years in a patient on [combination antiretroviral therapy],” the authors wrote, calling for a better understanding of the contribution these clonal cells make to the replication-competent viral reservoir, and how to target and eliminate them.
The study was supported by the National Cancer Foundation, the National Institutes of Health, Leidos Biomedical Research, and the F. M. Kirby Foundation. One author declared a consultancy for Gilead Sciences and shares in Cocrystal. No other conflicts of interest were declared.