Atypical HIV-1 Viremia Persistently Detected Exclusively Through the Pol Target by a Dual-Target (Pol and LTR) Assay: A Case Report About a New Diagnostic Challenge

We report the case of a 48-year-old man admitted with severe pneumonia, profound immunosuppression and multiple co-infections, showing unusual pattern of HIV-1 viremia. With the Aptima HIV-1 Quant Dx assay, a dual-target diagnostic assay for monitoring of viral RNA in people living with HIV-1 (PWH), the patient showed viral RNA consistently detected exclusively through the pol target, while the LTR signal remained absent in all samples during one year of follow-up on antiretroviral therapy. Despite this persistent atypical viral load (pol+/LTR-), near full-length next-generation sequencing of HIV-1 RNA confirmed an almost intact viral genome, including the LTR region and no resistance-associated mutations. Several mechanisms may account for explaining the persistent lack of LTR detection, such as defective quasi-species, RNA structural rearrangements, or epi-transcriptomic modifications interfering with primers annealing, and further studies are currently underway to clarify the biological origins and the clinical implications of the detection patterns of atypical HIV-1 RNA. The case described here is an example of a few PWH undergoing antiretroviral therapy who demonstrated single-target HIV-1 viremia with the Aptima dual-target assay. These particular clinical situations with single-target viremia, even at high levels of HIV-1 RNA, should be carefully considered in clinical management as they would indicate the presence of atypical viral RNA, for which, in some cases, switching antiretroviral therapy could be not necessary.