David B. Warner, Bennie H. Jeng, Jiyu Kim, Mengling Liu, Andrea B. Troxel, Judith S. Hochman, Keith H. Baratz, Shahzad I. Mian, Mazen Y. Choulakian, Jay J. Meyer, Ying Lu, Alberta Twi-Yeboah, Ting-Fang Lee, Carlos Lopez-Jimenez, Sarah C. Laury, Elisabeth J. Cohen, Sarah B Weissbart, Azin Abazari, Timothy Y Chou, Eileen Chang, Guillermo Amescua, Rahul Tonk, Elaine Koo, Jaime D Martinez, Anat Galor, Sanjay V Patel, John S Berestka, Afshan A Nanji, Winston Chamberlain, Richard Stutzman, John Clements, James Chodosh, Emma C Davies, Hajirah Saeed, Jessica B Ciralsky, Ana G Alzaga Fernandez, Kimberly C Sippel, Victor L Perez-Quinones, Melissa Daluvoy, Katy Liu, Mark D Ewald, Erich B Groos, Bernard Chang, Ira A Shivitz, Jordan Hill, Priscilla G Fowler, Russell W Read, Harry S Geggel, Ahmed Omar, Sayegh Rony, Christopher J Rapuano, Beeran Meghpara, Zeba Syed, Gary N Holland, Olivia Lee, John Irvine, Sophie X Deng, Anthony Aldave, Tsui Edmund, Judy Chen, Marc A Honig, Lee A Snyder, Andrew JW Huang, Todd P Margolis, Anthony Lubniewski, Douglas G Katz, Seema Capoor, John Gonzales, Gerami Seitzman, Jeremy Keenan, Melina Morkin, Kenneth R Kenyon, Pedram Hamrah, William B Lee, Joseph G Christenbury, Kara C LaMattina, Hyunjoo Lee, Kambiz Negahban, Ronihi Rao, Christine S Ament, Marta O Lopatynsky, John D Barbato, Jayati S Sarkar, Marian Macsai, Joshua B Herz, Mitchell P Weikert, Zaina Al-Mohtaseb, Alice Y Matoba, Theresa Cooney, Christopher Hood, Maria Woodward, Alan Sugar, Roni M Shtein, Sarah M Nehls, Evan J Warner, Greg Nettune, Brad Bowman, Henry Gelender, Jamie K Alexander, Tyrone McCall, Joshua Zaffos, Walter Beebe, Luke B Potts, Jay Lustbader, Aruoriwo M Oboh-Weilke, Kristin M Hammersmith, Stephen E Orlin, Parveen Nagra, Michael Sulewski, Vatinee Bunya, Brian Shafer, Christina R Prescott, Ilyse Haberman, Elizabeth Viriya, Anam Qureshi, Douglas Lazzaro, Laura Palazzolo, Himani Goyal, Katie E Schrack, Irving M Raber, Brandon Ayres, Brenton Finklea, Sherman Reeves, Omar E Awad, David R Hardten, Charles D Reilly, William J Flynn, Edward D Rashid, Angie E Wen, David C Ritterband, David J Harris, Sumayya Ahmad, Neha Shaik, John A Seedor, Steven I Rosenfeld, Marc Winnick, Ahmad Amir, Mark D Sherman, Divya Srikumaran, Esen Akpek, Benjamin Chaon, Sarkis H Soukiasian, Naveen K Rao, Anne S Steiner, Jules Winokur, Ira Udell, Carolyn Shih, Matthew Gorski, Amilia Schrier, Ann Marie Lobo-Chan, Joel Sugar, Elmer Tu, Wuqaas W Munir, Sarah Sunshine, Donald M Miller, William G Gensheimer, Michael E Zegans, Jayne S Weiss, Maria Bernal, Bruce Barron, Holly B Hindman, Ronald Wise, Christopher Gelston, Michael J Taravella, Richard S Davidson, Uyen L Tran, Christine Shieh, Jeremy Bartley, James McCulley, Steven Verity, Wayne Bowman, Preston Blomquist, Venkateswara V Mootha, George Thorne, Ann M Renucci, David Verdier, Kavitha Sivaraman, Michael Nordlund, Frank S Hwang, John Affeldt, Herbert Ingraham, Nathalie M Guibord, Kendall R B Dobbins, Tarika Thareja, Amy Lin, Brian Zaugg, Mark Mifflin, Stephan Lance Forstot, Robert A Fish, Karen Repine, Michael Wildes, Christopher B Estopinal, Donna Brown, Aaleya Koreishi, Patricia Ple-Plakon, Carol S Clemons, Ravi Patel, Penny A Asbell, Stephen Aaron Ashe, Sarah Bonaffini, Kourtney Houser, Michael Wallace, Jesse M Wesberry, Alfonso Iovieno, Sonia Yeung, Joshua C Teichman, Nima Noordeh, Anne Faucher, Marie-Claude Robert, Mona Harissi-Dagher, Jacob Rullo, Stephanie Baxter, Davin Johnson, Dean Mah, Matthew Benson, Stephan Ong Tone, Hall Chew, Mojgan Hassonlou, Shaohui Liu, Jennifer L Eikenberry, Chi-Wah Yung, Joanne F Shen, Charles Lin, Charles Yu, Christopher Ta, Kenneth R Goins, John Sutphin, Kerri Svanda, Stacy Keppol, Audrey Rostov, Neil M Vyas, Kimberly Hsu, Gerri Goodman, Lisa McHam, Dale Oates, Ramy Rizkalla, Anita Shukla, Mathew Veena, Craig See, Jeffrey Goshe, Robert S Feder, Jeanine Baqai, Surendra Basti, Ramez Haddadin, Jae Young You, Lena A Dixit, Ravi H Patel, Kimberly T Golde, Gerald W Zaidman, Sankara Mahesh, Vikas Sharma, Jason Wesolosky, Darby D Miller, Jeffrey H Ma, Mark Mannis, Rachael Niederer

Evidence regarding suppressive valacyclovir treatment on postherpetic neuralgia is necessary to guide care. To test the hypothesis that suppressive treatment with 1000 mg/d of oral valacyclovir for 12 months reduces the prevalence, severity, and duration of postherpetic neuralgia compared with placebo at 12 and 18 months in participants with herpes zoster ophthalmicus (HZO). Multicenter, placebo-controlled randomized clinical trial including 527 immunocompetent, nonpregnant adults with history of HZO rash, documented keratitis, or iritis within 1 year and an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater. The study was conducted at 95 participating sites (in Canada, New Zealand, and the US) from November 2017 to June 2024 and participant visits occurred every 3 months. Treatment with 1000 mg/d of valacyclovir or placebo for 12 months. Prevalence of postherpetic neuralgia, severity as determined by pain score (a score of ≥3 on a scale of 1-10), pain duration (≥3 months after HZO onset), and total daily dose of pain medication. Of the 527 participants (490 completed 12 months of treatment and 460 completed 18 months), 73 (14%) had postherpetic neuralgia and were analyzed by age at HZO onset (<60 years or ≥60 years) and disease duration (recent [<6 months] or chronic [≥6 months]). Of the 73 participants with postherpetic neuralgia (34 in the valacyclovir group and 39 in the placebo group), the mean age was 62.4 years (SD, 13.6 years), 59% were female, 5% were Black or African American, and 10% were Hispanic. The prevalence of postherpetic neuralgia at 12 months was not reduced by valacyclovir (12/32 [38%]) compared with placebo (14/35 [40%]) (between-group difference, 2.5% [95% CI, -20.8% to 25.8%]; P>.99). The participants who were younger than 60 years at HZO onset and had a chronic disease duration had lower pain scores in the valacyclovir group (mean score, 0.3 [SD, 0.9]) vs the placebo group (mean score, 0.8 [SD, 1.9]) at 12 months (P = .045) and at 18 months (mean score, 0.2 [SD, 0.9] vs 1.0 [SD, 2.3], respectively; P = .02). There was a decrease in pain duration in the valacyclovir group at 18 months (mean, 13.6 [SD, 11.4] months) vs the placebo group (mean, 18.7 [SD, 29.5] months) (linear mixed-effects model between-group difference, -3.39 months [95% CI, -6.73 to -0.04 months]; P = .046). The total daily dose of neuropathic pain medication was lower in the valacyclovir group (mean, 271.4 [SD, 593.8] mg/d) vs the placebo group (mean, 363.4 [SD, 592.2] mg/d) at 12 months (linear mixed-effects model P = .006) and at 18 months (mean, 209.0 [SD, 412.8] mg/d vs 286.2 [SD, 577.9] mg/d, respectively; linear mixed-effects model P = .01). One year of suppressive treatment with valacyclovir was associated with a lower dosage of neuropathic pain medication. Participants in the valacyclovir group, who were younger at HZO onset and had a chronic disease duration, had lower pain scores. These secondary outcomes support consideration of 1 year of suppressive treatment with valacyclovir to reduce dosage of pain medications and pain due to HZO. ClinicalTrials.gov Identifier: NCT03134196.