Christie Joya1,2, Seung Hyun Won1,3, Christina Schofield1,4, Tahaniyat Lalani1,3,5, Ryan C Maves1,6, Karl Kronmann1,5, Robert Deiss1, Jason Okulicz1,7, Brian K Agan1,3, Anuradha Ganesan1,2,3. 1. Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland. 2. Division of Infectious Diseases, Walter Reed National Military Medical Center, Bethesda, Maryland. 3. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland. 4. Division of Infectious Diseases, Madigan Army Medical Center, Tacoma, Washington. 5. Division of Infectious Diseases, Naval Medical Center Portsmouth, Virginia. 6. Division of Infectious Diseases, Naval Medical Center San Diego, California. 7. Infectious Disease Service, San Antonio Military Medical Center, Texas.
Abstract
BACKGROUND: Whether persistent low-level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the US Military HIV Natural History Study (NHS), to examine the association of pLLV and VF. METHODS: NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had 2 or more VLs measured with a lower limit of detection of ≤50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL >1000 copies/mL. Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (VL of 50-199 copies/mL on <25% of measurements), pLLV (VL of 50-199 copies/mL on ≥25% of measurements), high-level viremia (hLV) (VL of 200-1000 copies/mL), and continuous suppression (all VL <50 copies/mL). Cox proportional hazards models were used to evaluate the association between VF and LLV; hazard ratios and 95% confidence interval (CI) are presented. RESULTS: Two thousand six subjects (median age 29.2 years, 93% male, 41% black) were included; 383 subjects (19%) experienced VF. After adjusting for demographics, VL, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to ART start, pLLV (3.46 [2.42-4.93]), and hLV (2.29 [1.78-2.96]) were associated with VF. Other factors associated with VF include black ethnicity (1.33 [1.06-1.68]) and antiretroviral use prior to ART (1.79 [1.34-2.38]). Older age at ART initiation (0.71 [0.61-0.82]) and non-nucleoside reverse transcriptase inhibitor (0.68 [0.51-0.90]) or integrase strand transfer inhibitor use (0.26 [0.13-0.53]) were protective. CONCLUSION: Our data add to the body of evidence that suggests persistent LLV is associated with deleterious virologic consequences.
BACKGROUND: Whether persistent low-level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the US Military HIV Natural History Study (NHS), to examine the association of pLLV and VF. METHODS:NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had 2 or more VLs measured with a lower limit of detection of ≤50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL >1000 copies/mL. Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (VL of 50-199 copies/mL on <25% of measurements), pLLV (VL of 50-199 copies/mL on ≥25% of measurements), high-level viremia (hLV) (VL of 200-1000 copies/mL), and continuous suppression (all VL <50 copies/mL). Cox proportional hazards models were used to evaluate the association between VF and LLV; hazard ratios and 95% confidence interval (CI) are presented. RESULTS: Two thousand six subjects (median age 29.2 years, 93% male, 41% black) were included; 383 subjects (19%) experienced VF. After adjusting for demographics, VL, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to ART start, pLLV (3.46 [2.42-4.93]), and hLV (2.29 [1.78-2.96]) were associated with VF. Other factors associated with VF include black ethnicity (1.33 [1.06-1.68]) and antiretroviral use prior to ART (1.79 [1.34-2.38]). Older age at ART initiation (0.71 [0.61-0.82]) and non-nucleoside reverse transcriptase inhibitor (0.68 [0.51-0.90]) or integrase strand transfer inhibitor use (0.26 [0.13-0.53]) were protective. CONCLUSION: Our data add to the body of evidence that suggests persistent LLV is associated with deleterious virologic consequences.
Authors: D V Havlir; R Bassett; D Levitan; P Gilbert; P Tebas; A C Collier; M S Hirsch; C Ignacio; J Condra; H F Günthard; D D Richman; J K Wong Journal: JAMA Date: 2001-07-11 Impact factor: 56.272
Authors: A Gonzalez-Serna; L C Swenson; B Watson; W Zhang; A Nohpal; K Auyeung; J S Montaner; P R Harrigan Journal: Clin Microbiol Infect Date: 2016-08-30 Impact factor: 8.067
Authors: Gabriel M Ortiz; Jennifer Hu; Joshua A Goldwitz; Rohit Chandwani; Marie Larsson; Nina Bhardwaj; Sebastian Bonhoeffer; Bharat Ramratnam; Linqi Zhang; Martin M Markowitz; Douglas F Nixon Journal: J Virol Date: 2002-01 Impact factor: 5.103
Authors: Patrick Ryscavage; Sean Kelly; Jonathan Z Li; P Richard Harrigan; Babafemi Taiwo Journal: Antimicrob Agents Chemother Date: 2014-04-14 Impact factor: 5.191
Authors: Gisela Leierer; Katharina Grabmeier-Pfistershammer; Andrea Steuer; Mario Sarcletti; Maria Geit; Bernhard Haas; Ninon Taylor; Manfred Kanatschnig; Michaela Rappold; Bruno Ledergerber; Robert Zangerle Journal: Open Forum Infect Dis Date: 2016-06-15 Impact factor: 3.835
Authors: Rupa Kanapathipillai; Hamish McManus; Adeeba Kamarulzaman; Poh Lian Lim; David J Templeton; Matthew Law; Ian Woolley Journal: PLoS One Date: 2014-02-07 Impact factor: 3.240
Authors: Gisela Leierer; Katharina Grabmeier-Pfistershammer; Andrea Steuer; Maria Geit; Mario Sarcletti; Bernhard Haas; Manfred Kanatschnig; Michaela Rappold; Robert Zangerle; Bruno Ledergerber; Ninon Taylor Journal: PLoS One Date: 2015-11-13 Impact factor: 3.240
Authors: Brandon Carney; Colton Daniels; Xiaohe Xu; Thankam Sunil; Anuradha Ganesan; Jason M Blaylock; Karl C Kronmann; Christina Schofield; Tahaniyat Lalani; Brian Agan; Jason F Okulicz Journal: AIDS Res Ther Date: 2021-05-12 Impact factor: 2.250
Authors: Olof Elvstam; Gaetano Marrone; Patrik Medstrand; Carl Johan Treutiger; Anders Sönnerborg; Magnus Gisslén; Per Björkman Journal: Clin Infect Dis Date: 2021-06-15 Impact factor: 9.079
Authors: Hanna Brattgård; Per Björkman; Piotr Nowak; Carl Johan Treutiger; Magnus Gisslén; Olof Elvstam Journal: PLoS One Date: 2022-05-17 Impact factor: 3.240