by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

March 29, 2022

Featured Literature:
Eshleman SH, Fogel JM, Piwowar-Manning E, et al.  Characterization of Human Immunodeficiency Virus (HIV) infections in women who received injectable cabotegravir or tenofovir disoproxil fumarate/emtricitabine for HIV prevention: HPTN 084.  J Infect Dis.  2022 March 18; jiab576.  doi: 10.1093/infdis/jiab576.  PMID: 35301540.  Online ahead of print. 

This study describes baseline and incident HIV infections observed among 3,224 cisgender women enrolled in HPTN084.  Results of HIV diagnostic testing, viral load testing including a single-copy RNA assay, resistance testing, and study drug concentration analysis are included.  Three incident infections were identified among participants receiving cabotegravir (CAB) and 36 incident infections were identified among participants receiving TDF/FTC.  Incident infections in the CAB arm included 2 participants with no recent drug exposure and no injections (testing suggested low/no adherence to blinded oral CAB), and 1 participant with delayed injections: for this case, 3 out of 9 injections occurred outside protocol-specified allowable windows.  In all 3 incident CAB cases, CAB concentration at the first HIV-positive visit was below the level predicted to be protective based on non-human primate SHIV challenge studies.  No cabotegravir resistance was identified.  In 35 of the 36 TDF/FTC incident infection cases, suboptimal drug concentrations near the time of the first HIV-positive visit indicated low or no adherence.  The M184V mutation was identified in 1 participant in the TDF/FTC arm: investigators were unable to determine whether this was acquired from study drug exposure.  In 1 CAB and 8 TDF/FTC cases, retrospective testing revealed a delay between the first HIV-positive visit and the first site-positive visit (delay was longer for the participant receiving CAB compared to participants on TDF/FTC).

Author’s Commentary:

Results from HPTN084 indicate both long-acting cabotegravir and oral TDF/FTC are highly effective for HIV prevention in cisgender women.  However, detailed characterization of cases of HIV acquisition in the setting of pre-exposure prophylaxis use help advance our understanding of how medication exposure may affect HIV infection detection, inform optimal HIV testing approaches for persons initiating/maintained on PrEP, increase understanding of gender differences in adherence “forgiveness” of TDF/FTC, and also – importantly—inform implementation of long-acting cabotegravir as PrEP in real-world settings.  Additional results from HPTN084 and 083 (both have transitioned to open-label extension studies) are expected to provide further insight; authors also note “ongoing analysis …  from the two trials will provide more information about the correlates of HIV protection with CAB-LA PrEP [and its impact] on viral replication, antibody expression, and drug resistance.”          

The author has no conflicts of interest to disclose.

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