Background:
HPTN 083 and HPTN 084 demonstrated that long-acting injectable cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) was superior to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention. Twenty HIV infections were detected in the cabotegravir (CAB) arm during the blinded phase of the trials (5 baseline infections; 15 incident infections; 16 in HPTN 083 over 3,205 person-years; 4 in HPTN 084 over 1956 person-years). Characterization of these infections led to recognition of a novel syndrome that occurs in persons who acquire HIV infection in the setting of CAB-LA PrEP.
Methods:
Virology assessments included use of an antigen/antibody test, a discriminatory test, RNA assays, an ultrasensitive HIV DNA test, and HIV genotyping with standard and low viral load testing. Liquid chromatography-tandem mass spectrometry was used to measure CAB concentrations.
Results:
Infections that occurred within six months of CAB-LA exposure had clinical and laboratory features that were distinct from those usually seen in acute HIV infection and had minimal or no clinical symptoms. In most cases, viral replication was suppressed and antibody production was diminished/delayed for long periods. HIV DNA levels were undetectable or low in half of the cases where testing was performed. Seven infections occurred with no recent CAB exposure; these infections were detected using standard HIV testing algorithms. In contrast, detection of infection was delayed using standard HIV testing algorithms in 12 of 13 remaining cases. Major integrase strand transfer inhibitor (INSTI) resistance mutations were observed in seven cases. Delayed detection of infection in this setting led to inadvertent administration of CAB-LA to persons with undiagnosed infection in 11 cases.
Conclusions:
Detailed characterization of HIV infections in the setting of CAB-LA PrEP defined a new syndrome which we term the long-acting early viral inhibition syndrome (LEVI). This syndrome was associated with diagnostic delays using standard local HIV testing algorithms, INSTI resistance risk, and CAB-LA administration after infection. The prolonged viral suppression observed with CAB-LA PrEP suggests that there may be limited seeding of the HIV reservoir in early infection. Future studies are needed to evaluate the potential for HIV cure in this setting.