Background
Data on antiretroviral therapy (ART) outcomes in persons who acquire HIV with long-acting cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) are limited. We evaluated ART outcomes in CAB-LA exposed cisgender men and transgender women who have sex with men (MSM/TGW) who acquired HIV in the HPTN 083 trial. ART regimens were selected at study sites; local genotyping results were available in some cases.
Methods
Participants diagnosed with HIV after ≥1 CAB-LA injection with >30 days follow-up on ART were included (1st HIV positive visit through 12/1/23). HIV viral load (VL) and HIV genotyping data reported here are from retrospective centralized testing.
Results
Response to an initial ART regimen was assessed for 47 participants (Table): 22 on integrase strand transfer inhibitor (INSTI)-based ART and 25 on other ART (14 on efavirenz [EFV]-based ART; 10 on PI-based ART; 1 on PI+INSTI ART). Those with no CAB-LA in the past 6 months were more likely to start INSTI-based ART and less likely to have pre-ART INSTI resistance. Median follow-up on ART was shorter for those on INSTI-ART than for those on other ART regimens. The proportion of persons with VL <50 c/mL at the last visit was similar for the two groups. Two participants with pre-ART INSTI resistance started INSTI-ART: one with N155N/H+R263R/K who had a VL of 52 c/mL after 77 days on ART; one with R263K who had VL <50 c/mL from day 112 through day 356 on ART. ART outcomes were also assessed in 7 participants who switched to INSTI-based ART (4 cases above + 3 other cases; 2 from EFV-based ART; 3 from PI-based ART, 2 from PI+INSTI ART; median 2nd regimen follow-up: 219 days, range 145-349). All 7 participants achieved a VL <50 c/mL on the second regimen including one with pre-ART INSTI resistance (Q148R).
Conclusions
Ideal PrEP product profiles consider the potential for emergence of resistance to first-line ART. Some persons who acquire HIV with CAB LA-PrEP develop INSTI resistance which could compromise response to INSTI-based regimens. We found similar short-term ART outcomes for MSM/TGW who acquired HIV with CAB-LA PrEP with INSTI-ART vs. other ART regimens. These results should be interpreted with caution, since site location, rationale for ART selection, availability of local resistance testing, and differences in duration of follow-up complicate interpretation of these data. More data are needed to determine optimal ART regimen selection in persons who acquire HIV in the setting of CAB-LA PrEP.