The impact of PrEP during HIV acquisition may alter reservoir establishment, viral load set points, and immune responses. Some individuals on PrEP may remain negative by screening assays while still becoming infected. Characterization of such individuals is needed to define how to diagnose early infection in this context.
Working with the San Francisco Department of Public Health, we identified individuals with early HIV infection, many of whom were on PrEP. The estimated date of detected infection (EDDI) was calculated; standard diagnostic and resistance testing was performed.
58 participants (all men) with early HIV enrolled from 2015-2019. Most had sex with men (87%); median (IQR) age was 30 (25-37) years; pre-ART CD4 508 (355-680); log plasma HIV RNA 5.1 (4.1-5.7); time between EDDI and ART 29 (20-91) days. Among 24 with PrEP exposure, 13 (54%) reported prior use (>10 days pre-diagnosis), 6 (25%) active use (≤10 days pre-diagnosis), and 5 (21%) were found to have HIV on the day of PrEP initiation. The 6 reporting active PrEP at diagnosis had lower initial log plasma HIV RNA (2.8 vs 5.3, p=0.001) and higher CD4 (768 vs 488, p=0.03) than the 52 not on PrEP. The remaining analyses focus on those on active PrEP and those positive at PrEP initiation (n=11, Table). HIV Ab screening was positive in only 4/11 (36%). HIV RNA was detected in all cases, although <100 copies/mL in one and <20 copies/mL in two. Of these two, one had a newly positive Ab/Ag test, with cell-associated (CA)-DNA not detected and CA-RNA 117 copies/10^6 cells. The second had a negative Ab/Ag test and analysis of 25M PBMCs did not show CA-DNA or CA-RNA despite transiently detectable HIV RNA on clinical assays. Of the 8/11 who could have genotypic resistance testing, three had M184V/I mutations, with two transmitted and one emerging after 5 days on PrEP.
Increasingly widespread PrEP use may result in distinct and challenging presentations of HIV infection. We present the largest case series of early (or pre-existing) HIV on PrEP, with resultant blunting of immune responses and viral loads. Those presenting with delayed evidence of infection may be continued on PrEP, resulting in suboptimal treatment and development of resistance. In some cases, diagnostic uncertainty will arise regarding whether infection was prevented or established with a more limited reservoir. Further characterization of infections during PrEP is needed.