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

Deborah Donnell,Kenneth Fife,Eric Ramos,Allan Ronald,Connie Celum,Jared Baeten,Joan Dragavon,Robert W Coombs,Jordan Tappero,Jairam R Lingappa

doi:10.1097/qad.0000000000001577

Abstract

To investigate whether oral preexposure prophylaxis (PrEP) alters timing and patterns of seroconversion when PrEP use continues after HIV-1 infection. 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. 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. 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. Ongoing PrEP use in seroconverters may delay detection of infection and elongate seroconversion, although the delay does not increase risk of resistance.

Highlights

Multiple randomized clinical trials have shown that with good adherence, preexposure prophylaxis (PrEP), substantially reduces risk of HIV-1 acquisition [1,2,3,4,5,6]
No differences were found in Architect signal to cut-off (S/CO) comparing PrEP with placebo in as-randomized or as-treated comparisons (Fig. 3). In this analysis of a randomized, placebo controlled trial of PrEP, we showed that PrEP delayed the time to detect seroconversion for those participants who continued to take PrEP during acute/early clade C HIV-1 infection
The 2015 WHO recommendation that PrEP be implemented as part of an effective prevention package for persons at substantial risk of HIV-1 infection is leading to increasing scale-up of PrEP

Summary

Introduction

Multiple randomized clinical trials have shown that with good adherence, preexposure prophylaxis (PrEP), substantially reduces risk of HIV-1 acquisition [1,2,3,4,5,6] This prevention strategy requires frequent high-quality HIV-1 testing among PrEP users to detect acute/early HIV-1 infection and minimize risk of resistance. Nonadherence to PrEP provides little HIV-1 protection but at the same time little risk of resistance if the patient is infected [7], whereas high adherence to PrEP blocks most transmissions [8] For those who acquire HIV-1 in spite of PrEP – whether from sporadic adherence, or potentially a breakthrough with high adherence – it is unknown if PrEP use modifies the progression of seroconversion or the natural evolution of HIV-1 biomarkers. The Fiebig stages document the progression of infection from an initial ‘eclipse phase’ in local mucosal tissue, through dissemination to regional lymph nodes to systemic spread accompanied by high levels of HIV-1 replication in the blood [10,11]

Methods

Results

Discussion

Conclusion