Features of HIV Infection in the Context of Long-Acting Cabotegravir Preexposure Prophylaxis

   This letter outlines unusual clinical and laboratory features of HIV infection during long-acting cabotegravir (CAB-LA) preexposure prophylaxis (PrEP), observed in the HPTN 083 and 084 trials. The phenomenon termed long-acting early viral inhibition (LEVI) is characterized by smoldering viral replication, low or undetectable viral load, diminished or delayed antibody production, and minimal symptoms. Standard screening methods (rapid antigen-antibody assays) often miss LEVI cases or yield false negatives or reversions, delaying diagnosis. Of the 41 HIV infections among CAB-LA recipients, 17 showed delayed detection; 14 had received injections within 6 months, and 10 developed integrase strand transfer-inhibitor (INSTI) resistance especially among male-assigned participants with on-time injections. HIV RNA testing detects infection earlier and before resistance emerges, but false positives complicate interpretation.

   This letter outlines unusual clinical and laboratory features of HIV infection during long-acting cabotegravir (CAB-LA) preexposure prophylaxis (PrEP), observed in the HPTN 083 and 084 trials. The phenomenon termed long-acting early viral inhibition (LEVI) is characterized by smoldering viral replication, low or undetectable viral load, diminished or delayed antibody production, and minimal symptoms. Standard screening methods (rapid antigen-antibody assays) often miss LEVI cases or yield false negatives or reversions, delaying diagnosis. Of the 41 HIV infections among CAB-LA recipients, 17 showed delayed detection; 14 had received injections within 6 months, and 10 developed integrase strand transfer-inhibitor (INSTI) resistance especially among male-assigned participants with on-time injections. HIV RNA testing detects infection earlier and before resistance emerges, but false positives complicate interpretation.