The effect of oral preexposure prophylaxis on the progression of HIV-1 seroconversion

Partners PrEP Study Team

Research output: Contribution to journalArticle

Abstract

Objective: To investigate whether oral preexposure prophylaxis (PrEP) alters timing and patterns of seroconversion when PrEP use continues after HIV-1 infection. Design: Retrospective testing of the timing of Fiebig stage HIV-1 seroconversion in the Partners PrEP Study, a randomized placebo-controlled clinical trial of PrEP conducted in Kenya and Uganda. Methods: Specimens from 138 seroconverters were collected every 3 months and when HIV-1 infection was suspected based on monthly rapid HIV-1 tests. Progression of seroconversion was compared between randomized groups (PrEP versus placebo) and per-protocol groups (placebo versus PrEP participants with detectable tenofovir during the seroconversion period) using laboratory assessment of Fiebig stage. Delay in site-detection of seroconversion and association with PrEP drug-regimen resistant virus were assessed using logistic regression. Analysis of time to each Fiebig stage used maximum likelihood estimation with a parametric model to accommodate the varying lengths of HIV-infection intervals. Results: There was a significant increase in delayed site detection of infection associated with PrEP (odds ratio==3.49, P==0.044). Delay in detection was not associated with increased risk of resistance in the PrEP arm (odds ratio==0.93, P==0.95). Estimated time to each Fiebig stage was elongated in seroconverters with evidence of ongoing PrEP use, significantly for only Stage 5 (28 versus 17 days, P==0.05). Adjusted for Fiebig stage, viral RNA was ∼2/3 log lower in those assigned to PrEP compared with placebo; no differences were found in Architect signal to cut-off at any stage. Conclusion: Ongoing PrEP use in seroconverters may delay detection of infection and elongate seroconversion, although the delay does not increase risk of resistance.

Original languageEnglish (US)
Pages (from-to)2007-2016
Number of pages10
JournalAIDS
Volume31
Issue number14
DOIs
StatePublished - Sep 10 2017
Externally publishedYes

Fingerprint

HIV Seropositivity
HIV-1
Placebos
HIV Infections
Tenofovir
Odds Ratio
Uganda
Kenya
Viral RNA
Infection
Randomized Controlled Trials
Logistic Models
Seroconversion
Viruses
Pharmaceutical Preparations

Keywords

  • early HIV-1 seroconversion
  • Fiebig stages
  • HIV-1 RNA
  • HIV-1 testing
  • preexposure prophylaxis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

The effect of oral preexposure prophylaxis on the progression of HIV-1 seroconversion. / Partners PrEP Study Team.

In: AIDS, Vol. 31, No. 14, 10.09.2017, p. 2007-2016.

Research output: Contribution to journalArticle

Partners PrEP Study Team. / The effect of oral preexposure prophylaxis on the progression of HIV-1 seroconversion. In: AIDS. 2017 ; Vol. 31, No. 14. pp. 2007-2016.
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abstract = "Objective: To investigate whether oral preexposure prophylaxis (PrEP) alters timing and patterns of seroconversion when PrEP use continues after HIV-1 infection. Design: Retrospective testing of the timing of Fiebig stage HIV-1 seroconversion in the Partners PrEP Study, a randomized placebo-controlled clinical trial of PrEP conducted in Kenya and Uganda. Methods: Specimens from 138 seroconverters were collected every 3 months and when HIV-1 infection was suspected based on monthly rapid HIV-1 tests. Progression of seroconversion was compared between randomized groups (PrEP versus placebo) and per-protocol groups (placebo versus PrEP participants with detectable tenofovir during the seroconversion period) using laboratory assessment of Fiebig stage. Delay in site-detection of seroconversion and association with PrEP drug-regimen resistant virus were assessed using logistic regression. Analysis of time to each Fiebig stage used maximum likelihood estimation with a parametric model to accommodate the varying lengths of HIV-infection intervals. Results: There was a significant increase in delayed site detection of infection associated with PrEP (odds ratio==3.49, P==0.044). Delay in detection was not associated with increased risk of resistance in the PrEP arm (odds ratio==0.93, P==0.95). Estimated time to each Fiebig stage was elongated in seroconverters with evidence of ongoing PrEP use, significantly for only Stage 5 (28 versus 17 days, P==0.05). Adjusted for Fiebig stage, viral RNA was ∼2/3 log lower in those assigned to PrEP compared with placebo; no differences were found in Architect signal to cut-off at any stage. Conclusion: Ongoing PrEP use in seroconverters may delay detection of infection and elongate seroconversion, although the delay does not increase risk of resistance.",
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author = "{Partners PrEP Study Team} and Deborah Donnell and Eric Ramos and Connie Celum and Jared Baeten and Joan Dragavon and Jordan Tappero and Lingappa, {Jairam R.} and Allan Ronald and Kenneth Fife and Coombs, {Robert W.} and Lisa Frenkel and Craig Hendrix and McElrath, {M. Juliana}",
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AU - Donnell, Deborah

AU - Ramos, Eric

AU - Celum, Connie

AU - Baeten, Jared

AU - Dragavon, Joan

AU - Tappero, Jordan

AU - Lingappa, Jairam R.

AU - Ronald, Allan

AU - Fife, Kenneth

AU - Coombs, Robert W.

AU - Frenkel, Lisa

AU - Hendrix, Craig

AU - McElrath, M. Juliana

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AB - Objective: To investigate whether oral preexposure prophylaxis (PrEP) alters timing and patterns of seroconversion when PrEP use continues after HIV-1 infection. Design: Retrospective testing of the timing of Fiebig stage HIV-1 seroconversion in the Partners PrEP Study, a randomized placebo-controlled clinical trial of PrEP conducted in Kenya and Uganda. Methods: Specimens from 138 seroconverters were collected every 3 months and when HIV-1 infection was suspected based on monthly rapid HIV-1 tests. Progression of seroconversion was compared between randomized groups (PrEP versus placebo) and per-protocol groups (placebo versus PrEP participants with detectable tenofovir during the seroconversion period) using laboratory assessment of Fiebig stage. Delay in site-detection of seroconversion and association with PrEP drug-regimen resistant virus were assessed using logistic regression. Analysis of time to each Fiebig stage used maximum likelihood estimation with a parametric model to accommodate the varying lengths of HIV-infection intervals. Results: There was a significant increase in delayed site detection of infection associated with PrEP (odds ratio==3.49, P==0.044). Delay in detection was not associated with increased risk of resistance in the PrEP arm (odds ratio==0.93, P==0.95). Estimated time to each Fiebig stage was elongated in seroconverters with evidence of ongoing PrEP use, significantly for only Stage 5 (28 versus 17 days, P==0.05). Adjusted for Fiebig stage, viral RNA was ∼2/3 log lower in those assigned to PrEP compared with placebo; no differences were found in Architect signal to cut-off at any stage. Conclusion: Ongoing PrEP use in seroconverters may delay detection of infection and elongate seroconversion, although the delay does not increase risk of resistance.

KW - early HIV-1 seroconversion

KW - Fiebig stages

KW - HIV-1 RNA

KW - HIV-1 testing

KW - preexposure prophylaxis

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