While rare, HIV seroconversions have occurred among people taking long-acting injectable cabotegravir (CAB-LA) for PrEP. Of concern for HIV clinicians in these cases is a phenomenon known as long-acting early viral inhibition, or LEVI syndrome.
LEVI syndrome typically occurs when a person is receiving long-acting antiretrovirals during the acute phase of HIV. This can result in a delayed immune response, rendering HIV RNA initially undetectable, limiting the generation of antibodies, and potentially leading to delayed diagnosis.
However, data presented at the 5th HIV Research for Prevention Conference (HIVR4P 2024) in Lima, Peru, may attenuate some of these concerns. The findings highlight the initial success of antiretroviral therapy in three people who had experienced breakthrough HIV acquisition while on CAB-LA despite on-time injections.
The study results, presented by Urvi M. Parikh, Ph.D., appear to be the first case series reported following HIV acquisition on CAB-LA PrEP in routine clinical care in the U.S. Parikh is an associate professor of medicine at the University of Pittsburgh and associate director of the virology core laboratory there.
The number of CAB-LA injections received prior to a patient’s HIV diagnosis ranged from five to 13 in the study. Time between the last injection and HIV diagnosis ranged from 21 to 55 days. In all instances, there were detectable concentrations of CAB-LA at the time of diagnosis.
In all three instances, protease inhibitor–based antiretroviral therapy (ART) with darunavir was initiated. However, in one case, this was switched to an INSTI-based regimen containing bictegravir. At around five months of follow-up, all cases had achieved viral suppression.
Though the findings are encouraging, Parikh noted that questions remain regarding which CAB-LA–selected mutations have the greatest impact on treatment outcomes on INSTI-based ART, as well as the long-term durability of viral suppression when introducing INSTI-based ART in those who acquired HIV while on CAB-LA. These concerns are related to the fact that cabotegravir belongs to the integrase inhibitor drug class; widely used medications for the treatment of HIV, such as dolutegravir, also belong to this class.