Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov:148:107222.
doi: 10.1016/j.ijid.2024.107222. Epub 2024 Aug 24.

Suppressed HIV antibody responses following exposure to antiretrovirals-evidence from PrEP randomized trials and early antiretroviral treatment initiation studies

Vivian I Avelino-Silva  1 , Mars Stone  2 , Sonia Bakkour  2 , Clara Di Germanio  2 , Michael Schmidt  3 , Ashtyn L Conway  4 , David Wright  5 , Eduard Grebe  2 , Brian Custer  2 , Steven H Kleinman  6 , Xutao Deng  2 , Jairam R Lingappa  7 , Patricia Defechereux  8 , Megha Mehrotra  8 , Robert M Grant  8 , Sandhya Vasan  9 , Shelley Facente  10 , Nittaya Phanuphak  11 , Carlo Sacdalan  12 , Siriwat Akapirat  13 , Mark de Souza  14 , Michael P Busch  2 , Philip J Norris  15 ; NHLBI Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P)
Affiliations

Suppressed HIV antibody responses following exposure to antiretrovirals-evidence from PrEP randomized trials and early antiretroviral treatment initiation studies

Vivian I Avelino-Silva et al. Int J Infect Dis. 2024 Nov.

Abstract

Background: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening.

Methods: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP).

Results: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users. Among RV254 participants, reactivity in Ag/Ab assays was <100% at all timepoints, and lower among those initiating ART earlier. Seroreversions occurred for 29% (16/55), and blood donation screening with NAT and Ag/Ab assays could have missed up to 36% (20/55) of RV254 participants. For SIPP participants, who started ART at later timepoints, Ag/Ab assays identified infections with no evidence of reactivity waning.

Conclusion: PrEP and early ART initiation can delay or reduce HIV detectability. Considerations for the implementation of NAT and Ag/Ab tests in PrEP/PEP programs relying on Ab-only RDTs should be balanced according to feasibility and public health impact. While blood transfusion services using Ab-only RDTs for HIV screening should adopt higher sensitivity tests, surveillance and further research are needed to determine the need for novel HIV testing algorithms for those already using NAT and Ag/Ab screening assays.

Keywords: Antiretroviral therapy; Delayed diagnosis; Diagnostics; HIV testing; Pre-exposure prophylaxis; Serologic tests.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SF has received consulting support from Gilead Sciences for unrelated work. MPB has received research support from Abbott, Grifols, Roche, and QuidelOrtho. He received no personal compensation, equity, advisory committee role or travel support. MLM is an employee and shareholder of Gilead Sciences. BC received research funding and reagents from Hologic and from Grifols Diagnostic Solutions and has been part of the speakers´ bureau of Abbott Inc. SB is an employee and received honoraria for lectures from Grifols Diagnostic Solutions.

Figures

Figure 1.
Figure 1.
Participants and samples included in the study. (a) Participants and samples from PrEP trials. (b) Participants and samples from early antiretroviral initiation studies.
Figure 2.
Figure 2.
Evidence of infection prior to detection by rapid tests, according to PrEP treatment assignment. (a) Percentages and 95% confidence intervals of positive results at each time interval prior to the date of the first positive rapid test according to treatment assignment. (b) Percentages and 95% confidence intervals with evidence of infection using antigen/antibody detection tests alone or in combination in samples collected up to 8 weeks prior to detection by rapid tests, according to PrEP treatment assignment. The combination of NAT and antigen/antibody tests increased positivity, although not reaching statistical significance when compared to antigen/antibody tests alone.
Figure 3.
Figure 3.
Antibody signals and corresponding smoothed splines in samples collected prior to detection by rapid test in PrEP trials. P-values calculated using repeated measures spline regressions comparing placebo and active PrEP groups.
Figure 4.
Figure 4.
Test positivity at and following early ART initiation in RV254. Percentages and 95% confidence intervals of positive test results in RV254 participants, overall and by Fiebig stage at ART initiation. Tests performed in all samples (N=55) with up to one missing observation per visit.
See this image and copyright information in PMC

References

    1. Fiebig EW, Wright DJ, Rawal BD, Garrett PE, Schumacher RT, Peddada L, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 2003;17(13):1871–9. - PubMed
    1. Delaney KP, Hanson DL, Masciotra S, Ethridge SF, Wesolowski L, Owen SM. Time until emergence of HIV test reactivity following infection with HIV-1: implications for interpreting test results and retesting after exposure. Clin Infect Dis 2017;64(1):53–9. - PubMed
    1. Vermeulen M, Van Schalkwyk C, Jacobs G, Van Den Berg K, Stone M, Bakkour S, et al. The impact of early antiretroviral treatment (ART) for HIV on the sensitivity of the latest generation of blood screening and point of care assays. Viruses 2022;14(7):1426. - PMC - PubMed
    1. Liang Y, Lin H, Dzakah EE, Tang S. Influence of combination antiretroviral therapy on HIV-1 serological responses and their implications: a systematic review and meta-analysis. Front Immunol 2022;13:844023. - PMC - PubMed
    1. Donnell D, Ramos E, Celum C, Baeten J, Dragavon J, Tappero J, et al. The effect of oral preexposure prophylaxis on the progression of HIV-1 seroconversion. AIDS 2017;31(14):2007–16. - PMC - PubMed