HPTN 083 and 084 demonstrated that long-acting injectable cabotegravir (CAB-LA) is highly effective for HIV prevention; rare breakthrough infections were observed. Detection of HIV infection in participants who received CAB PrEP was often delayed using standard HIV testing algorithms. In HPTN 083, integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in 5 CAB-exposed participants with HIV infection (GenoSure PRIME assay, viral load [VL] ?500 c/mL); 2 other participants did not have genotyping results since all VLs were <500 c/mL. In all 7 participants, detection of infection at study sites using rapid tests and antigen/antibody tests was delayed (median 60 days; range 35-117) and all 7 participants received CAB-LA injections after infection occurred. We used a single-genome sequencing (SGS) INSTI genotyping assay to assess whether earlier detection of these HIV infections would have provided an opportunity to start antiretroviral treatment (ART) before INSTI resistance emerged.
SGS testing was performed for 21 samples from the 7 participants described above (1 baseline infection; 6 incident infections). The 21 samples tested positive with Aptima HIV-1 RNA Qualitative Assay result (limit of detection [LOD]: 30 c/mL) and had VLs <500 c/mL. The Stanford HIV Drug Resistance Database was used for INSTI RAMs.
The SGS assay was successful for 18/21 samples tested. The assay detected INSTI RAMs in 6/7 participants (4/5 with prior genotyping results, 2/2 with no prior genotyping results). Use of an RNA assay with an LOD of 30 copies/mL detected infection before a major INSTI RAM was detected (4 cases) or before additional major INSTI RAMs accumulated (2 cases). In the last case, this could not be assessed since SGS was not successful before the first site-positive visit.
Consistent with newly released CDC guidelines, earlier detection of HIV infection using an HIV RNA assay in the setting of CAB-LA PrEP would allow for earlier ART initiation which may reduce the risk of INSTI resistance. Given the low levels of viremia often seen in this setting, VL testing for HIV screening should be performed using the most sensitive assay available. In the context of proven high efficacy, CAB-LA should also be considered for HIV PrEP in settings where HIV RNA screening is not readily available.