Impact of Tamoxifen on Vorinostat-Induced Human Immunodeficiency Virus Expression in Women on Antiretroviral Therapy: AIDS Clinical Trials Group A5366, The MOXIE Trial

Eileen P. Scully, Evgenia Aga, Athe Tsibris, Nancie Archin, Kate Starr, Qing Ma, Gene D. Morse, Kathleen E. Squires, Bonnie J. Howell, Guoxin Wu, Lara Hosey, Scott F. Sieg, Lynsay Ehui, Francoise Giguel, Kendyll Coxen, Curtis Dobrowolski, Monica Gandhi, Steve Deeks, Nicolas Chomont, Elizabeth ConnickCatherine Godfrey, Jonathan Karn, Daniel R. Kuritzkes, Ronald J. Bosch, Rajesh T. Gandhi

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


BACKGROUND: Biological sex and the estrogen receptor alpha (ESR1) modulate human immunodeficiency virus (HIV) activity. Few women have enrolled in clinical trials of latency reversal agents (LRAs); their effectiveness in women is unknown. We hypothesized that ESR1 antagonism would augment induction of HIV expression by the LRA vorinostat. METHODS: AIDS Clinical Trials Group A5366 enrolled 31 virologically suppressed, postmenopausal women on antiretroviral therapy. Participants were randomized 2:1 to receive tamoxifen (arm A, TAMOX/VOR) or observation (arm B, VOR) for 5 weeks followed by 2 doses of vorinostat. Primary end points were safety and the difference between arms in HIV RNA induction after vorinostat. Secondary analyses included histone 4 acetylation, HIV DNA, and plasma viremia by single copy assay (SCA). RESULTS: No significant adverse events were attributed to study treatments. Tamoxifen did not enhance vorinostat-induced HIV transcription (between-arm ratio, 0.8; 95% confidence interval [CI], .2-2.4). Vorinostat-induced HIV transcription was higher in participants with increases in H4Ac (fold increase, 2.78; 95% CI, 1.34-5.79) vs those 9 who did not (fold increase, 1.04; 95% CI, .25-4.29). HIV DNA and SCA plasma viremia did not substantially change. CONCLUSIONS: Tamoxifen did not augment vorinostat-induced HIV RNA expression in postmenopausal women. The modest latency reversal activity of vorinostat, postmenopausal status, and low level of HIV RNA expression near the limits of quantification limited assessment of the impact of tamoxifen. This study is the first HIV cure trial done exclusively in women and establishes both the feasibility and necessity of investigating novel HIV cure strategies in women living with HIV. CLINICAL TRIALS REGISTRATION: NCT03382834.

Original languageEnglish (US)
Pages (from-to)1389-1396
Number of pages8
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Issue number8
StatePublished - Oct 12 2022


  • ESR1
  • HIV cure
  • biological sex
  • latency reversal agent

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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