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Virological Blips and Predictors of Post Treatment Viral Control After Stopping ART Started in Primary HIV Infection

Fidler, Sarah MD; Olson, Ashley D. MA; Bucher, Heiner C.; Fox, Julie PhD; Thornhill, John PhD; Morrison, Charles MD; Muga, Roberto MD; Phillips, Andrew; Frater, John PhD; Porter, Kholoud

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 February 2017 - Volume 74 - Issue 2 - p 126–133
doi: 10.1097/QAI.0000000000001220
Epidemiology

Background: Few individuals commencing antiretroviral therapy (ART) in primary HIV infection (PHI) maintain undetectable viremia after treatment cessation. Associated factors remain unclear given the importance of the phenomenon to cure research.

Methods: Using CASCADE data of seroconverters starting ART in PHI (≤6 months from seroconversion), we estimated proportions experiencing viral blips (>400 copies followed by <400 copies HIV-RNA/mL without alteration of regimen) while on ART. We used Cox models to examine the association between time from ART stop to loss of control (2 consecutive measurements >1000 copies per milliliter) and magnitude and frequency of blips while on ART, time from seroconversion to ART, time on ART, adjusting for mean number of HIV-RNA measurements/year while on ART, and other confounders.

Results: Seven hundred seventy-eight seroconverters started ART in PHI with ≥3 HIV-RNA measurements. Median interquartile range (IQR) ART duration was 16.2 (8.0–35.9) months, within which we observed 13% with ≥1 blip. Of 228 who stopped ART, 119 rebounded; time to loss of control was associated with longer interval between seroconversion and ART initiation [hazard ratio (HR) = 1.16 per month; 1.04, 1.28], and blips while on ART (HR = 1.71 per blip; 95% confidence interval = 0.94 to 3.10). Longer time on ART (HR = 0.84 per additional month; 0.76, 0.92) was associated with lower risk of losing control. Of 228 stopping ART, 22 (10%) maintained post treatment control (PTC), ie, HIV-RNA <50 copies per milliliter ≥24 months after ART cessation.

Conclusion: HIV viral blips on therapy are associated with subsequent viral rebound on stopping ART among individuals treated in PHI. Longer duration on ART is associated with a greater chance of PTC.

*Department of Genitourinary Medicine and Infectious Disease, Imperial College, London, United Kingdom;

University College London, London, United Kingdom;

Medical Research Council Clinical Trials Unit at University College London, London, UK. Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland;

§Guys and St Thomas Hospital NHS Trust, London, United Kingdom;

Clinical and Epidemiological Sciences, FHI 360, Durham, NC;

Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; and

#Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, Oxford University, United Kingdom; Oxford Martin School, Oxford, United Kingdom; Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom.

Correspondence to: Sarah Fidler, MD, Wright Fleming Institute, Department of GUM and Communicable Diseases, Faculty of Medicine, Imperial College, St Mary's Hospital, London W2 1NY, United Kingdom (e-mail: S.fidler@imperial.ac.uk).

The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under EuroCoord Grant agreement no 260694 and Medical Research Council UK. Imperial College NIHR BRC supported S.F., J.T.

The authors have no conflicts of interest to disclose.

S.F., A.D.O., H.C.B., J. Fox, J. Frater, and K.P. contributed to study design, A.P., H.C.B., C.M., R.M., A.P., and K.P. contributed to data collection, S.F., A.D.O., H.C.B., J. Fox, J.T., C.M., R.M., A.P., J. Frater, and K.P. contributed to writing.

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received April 26, 2016

Accepted October 12, 2016

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.