To the Editor:

Drs. El-Haddad and Erlich review an important new option for preventing HIV infection.¹ Intramuscular cabotegravir (Apretude) is much more effective than daily oral tenofovir disoproxil fumarate/emtricitabine (Truvada) at preventing HIV infection.² As family physicians and HIV specialists, we are excited about this option but remain wary of its potential risks. One of the more serious risks is long-acting early viral inhibition syndrome, which can occur in people who acquire HIV infection despite appropriate use of intramuscular cabotegravir.³

Long-acting early viral inhibition syndrome presents with minimal symptoms, conflicting serology results that can revert to negative, and low or suppressed viral loads. These mild symptoms and ambiguous laboratory findings can culminate in months-long delays in diagnosis and development of resistance to integrase strand transfer inhibitor medications.³ This is concerning because the integrase strand transfer inhibitor drug class is a first-line treatment of HIV infection.⁴ Most concerning is that long-acting early viral inhibition syndrome can be found in people receiving on-time injections with adequate serum concentration levels of cabotegravir. Prescribers must be aware of this potential risk and adhere to the monitoring recommendations.

Awareness of long-acting early viral inhibition syndrome is vital to understanding the importance of the Centers for Disease Control and Prevention recommendation to monitor patients receiving intramuscular cabotegravir for preexposure prophylaxis (PrEP) for HIV every 2 months (i.e., with each administration) using an antigen-antibody assay and the more sensitive HIV-1 RNA assay.⁵ The sensitivity of the RNA assay allows for earlier detection of infection. It is also important to counsel patients on the cabotegravir “tail,” which is the long and highly variable time when cabotegravir is detectable after discontinuation but below the level of protection. For 12 months after discontinuation, patients should continue RNA testing for HIV every 3 months. If patients have an ongoing indication for PrEP, oral cabotegravir PrEP with tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine (Descovy) should be recommended to decrease the risk of acquiring HIV infection.⁵

The Clinician Consultation Center PrEPline (855-488-7737) is available on weekdays to help with ambiguous test results and provide recommendations for people who may have acquired HIV infection while taking PrEP. We recommend obtaining integrase strand transfer inhibitor genotype resistance testing for patients confirmed to have acquired HIV infection while taking cabotegravir; if antiretroviral therapy is initiated before receiving the results of resistance testing, the regimen should include darunavir (Prezista; a protease inhibitor) boosted with ritonavir or cobicistat.⁵

Editor's Note: This letter was sent to the authors of “Cabotegravir (Apretude) for Pre-exposure Prophylaxis for HIV Type 1 Infection,” who declined to reply.