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Vorinostat is in Phase 2 development as a latency-reversing agent for HIV.
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and Treatment Action Group website3)
What is vorinostat?
Vorinostat (brand name: Zolinza) is a drug that has been approved by the U.S.(FDA) for the treatment of cancer. It is also being studied as an as part of a strategy to cure HIV .3,4As an investigational HIV drug, vorinostat belongs to a group of drugs called .3
How do latency-reversing agents work?
Currently, there is no cure for HIV infection. One of the main obstacles to curing HIV infection is that thecan remain hidden and inactive (latent) inside certain cells of the (such as resting CD4 cells) for many months or even years. The cells where latent HIV hides are known as the . Because HIV in this latent state is inactive, the immune system cannot detect the virus, and the (ARV) drugs that are used to treat HIV have no effect on it.5-7
Latency-reversing agents work by drawing HIV out of its latent state within resting CD4 cells. Once the latent HIV is reactivated, the CD4 cells that harbor the virus are more likely to be recognized and killed by the body’s immune system or may be killed by certain HIV therapies, such as those that can enhance the body's What is a Latent HIV Reservoir? fact sheet.to HIV. Researchers hope that the combined use of vorinostat and other HIV-fighting strategies, including ongoing (ART), may fully eliminate HIV from the body.5-7To learn more, see the HIVinfo
Which clinical trials are studying vorinostat?
Study Name: NCT01319383
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to determine the effectiveness of vorinostat in activating latent HIV in resting CD4 cells after single and multiple vorinostat doses.8
Study Names: SEARCH 019; NCT02475915 and SEARCH 026; NCT02470351
Status: These studies have been completed.
Purpose: The SEARCH 019 study evaluated the safety and effectiveness of a that combined vorinostat, the drugs hydroxychloroquine and maraviroc, and ART in controlling levels during a treatment interruption.9,10
SEARCH 026 was a sub-study that was conducted at the same time as SEARCH 019 and included some of the SEARCH 019 participants. The sub-study evaluated how the treatment regimens used in SEARCH 019 affected the(CNS), latent HIV in the CNS, and viral load levels in the CNS of the participants.9,11
Study Name: NCT01365065
Status: This study has been completed.
Purpose: The purpose of this study was to determine whether vorinostat could activate latent HIV in resting CD4 cells of adults whose HIV was well controlled by ART.3,12
Study Names: RIVER trial; NCT02336074
Status: This study is ongoing, but not recruiting participants.
Location: United Kingdom
Purpose: The purpose of this study in participants with newly diagnosed HIV is to determine whether a combination of drugs can effectively reduce latent HIV in resting CD4 cells. The combination strategy will include ART, two therapeutic HIV vaccines, and vorinostat.13
Study Names: MOXIE trial; ACTG A5366; NCT03382834
Status: This study is ongoing, but not recruiting participants.
Location: United States and Puerto Rico
Purpose: The purpose of this study is to evaluate whether the therapy tamoxifen can enhance vorinostat’s ability to activate latent HIV in post-menopausal women with HIV.14
For more details on the studies listed above, see theHealth Professional versionof this drug summary.
Other HIV-related trials investigating vorinostat include:
- XTRA trial (NCT03212989): A Phase 1 study that will evaluate the effect of vorinostat used with specific types of immune cells (called expanded specific T-cell therapy) on HIV infection in adults. This study is currently recruiting participants.15
- VOR-07 study (NCT03803605): A Phase 1 study that will evaluate the effects of vorinostat and the investigational broadly neutralizing VRC07-523LS on HIV infection in adults. This study is ongoing, but not recruiting participants.16
What side effects might vorinostat cause?
One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of vorinostat listed above.
In this study, side effects reported by participants who received vorinostat included mild, temporary symptoms, headache, and low counts.17,18
SEARCH 019 (NCT02475915) and SEARCH 026 (NCT02470351):
In this Phase 1/2 study, two participants in the group taking vorinostat had serious side effects. One participant stopped the study because of poor kidney function and low platelet levels. The other participant had diarrhea that may have been caused by the study drugs or by food poisoning. When compared to participants in the ART-only group, more participants in the group taking vorinostat had low platelet levels and high creatinine levels. (High creatinine levels can mean that the aren’t working well.)9,19
In the sub-study, treatment with vorinostat did not result in the presence of HIV inor other lasting side effects.11,20
In this Phase 2 study, most of the side effects that occurred were not serious. The most common side effects were nausea, diarrhea, fatigue, and low platelet counts.21
RIVER trial (NCT02336074):
In this Phase 2 study, 97% of the participants who received ART plus two therapeutic HIV vaccines plus vorinostat had a side effect. Seventy percent of these side effects were mild and 23% were moderate in intensity. In comparison, 73% of participants receiving ART only had a side effect; 33% were mild and 20% were moderate. No treatment-related serious side effects were reported.13,22,23
MOXIE trial (NCT03382834):
In this Phase 2 study, 21 women were assigned to receive vorinostat plus tamoxifen and 10 women were assigned to receive voirnostat alone. No severe or life-threatening drug-related side effects were reported during the study.14,24
Because vorinostat is still being studied as an HIV drug, information on possible side effects of the drug is not complete. As testing of vorinostat continues, additional information on possible side effects will be gathered.
Additional information on side effects known to be associated with vorinostat can be found in the FDA-approved Full Prescribing Information for Zolinza.4
Where can I get more information about clinical trials studying vorinostat?
More information about vorinostat-related research studies is available from ClinicalTrials.gov.
Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a NIH Clinical Research Trials and You.is right for you. For more information, visit
- United States National Library of Medicine. ChemIDplus Advanced: Vorinostat. https://chem.nlm.nih.gov/chemidplus/rn/149647-78-9. Accessed May 29, 2020
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed May 29, 2020
- Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed May 29, 2020
- Merck Sharp & Dohme Corp. Zolinza: full prescribing information, January 2020. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid = cd86ee78-2781-468b-930c-3c4677bcc092. Accessed May 29, 2020
- Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1):a007096.
- Rasmussen TA, Tolstrup M, Winckelmann A, Østergaard L, Søgaard OS. Eliminating the latent HIV reservoir by reactivation strategies. Hum Vaccines Immunother. 2013;9(4):790–799.
- National Institute of Allergy and Infectious Diseases (NIAID). HIV viral eradication. https://www.niaid.nih.gov/diseases-conditions/hiv-viral-eradication. Accessed May 29, 2020
- University of North Carolina, Chapel Hill. A Phase I/II investigation of the effect of vorinostat (VOR) on HIV RNA expression in the resting CD4 T cells of HIV-infected patients receiving stable antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 17, 2011. NLM Identifier: NCT01319383. https://www.clinicaltrials.gov/ct2/show/NCT01319383. Accessed May 29, 2020
- South East Asia Research Collaboration with Hawaii. A randomized study to compare the efficacy of vorinostat/hydroxychloroquine/maraviroc (VHM) in controlling HIV after treatment interruption in subjects who initiated ART during acute HIV infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 3, 2015. NLM Identifier: NCT02475915. https://clinicaltrials.gov/ct2/show/NCT02475915. Accessed May 29, 2020
- Kroon E, Ananworanich J, Eubanks K, et al. Effect of vorinostat, hydroxychloroquine and maraviroc combination therapy on viremia following treatment interruption in individuals initiating ART during acute HIV infection. Abstract presented at: 21st International AIDS Conference (AIDS 2016); July 18-22, 2016; Durban, South Africa. Abstract TUAX0101LB. http://programme.aids2016.org/Abstract/Abstract/10535. Accessed May 29, 2020
- South East Asia Research Collaboration with Hawaii. Study SEARCH 026Assessment of the HIV CNS reservoir, neurological and neuro-cognitive effects, and source of rebound HIV in CNS in subjects participating in Study SEARCH 019. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 2, 2015. NLM Identifier: NCT02470351. https://clinicaltrials.gov/ct2/show/NCT02470351. Accessed May 29, 2020
- Bayside Health. A pilot study to assess the safety and effect on HIV transcription of vorinostat in patients receiving suppressive combination anti-retroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 1, 2011. NLM Identifier: NCT01365065. https://www.clinicaltrials.gov/ct2/show/NCT01365065. Accessed May 29, 2020
- Imperial College London. Research in viral eradication of HIV reservoirs. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 23, 2014. NLM Identifier: NCT02336074. https://www.clinicaltrials.gov/ct2/show/NCT02336074. Accessed May 29, 2020
- National Institute of Allergy and Infectious Diseases (NIAID). Selective estrogen receptor modulators to enhance the efficacy of viral reactivation with histone deacetylase inhibitors. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 19, 2017. NLM Identifier: NCT03382834. https://clinicaltrials.gov/ct2/show/record/NCT03382834. Accessed May 29, 2020
- University of North Carolina, Chapel Hill. IGHID 11627 - A Phase I study to evaluate the effects of vorinostat and HIV-1 antigen expanded specific T cell therapy (HXTC) on persistent HIV-1 infection in HIV-infected individuals started on antiretroviral therapy (The XTRA Study). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 11, 2018. NLM Identifier: NCT03212989. https://clinicaltrials.gov/ct2/show/study/NCT03212989. Accessed May 29, 2020
- University of North Carolina, Chapel Hill. IGHID 11802 - Combination Therapy With the Novel Clearance Modality (VRC07-523LS) and the Latency Reversal Agent (Vorinostat) to Reduce the Frequency of Latent, Resting CD4 T Cell Infection (The VOR-07 Study). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on: January 10, 2019. NLM Identifier: NCT03803605. https://clinicaltrials.gov/ct2/show/NCT03803605. Accessed May 29, 2020
- Archin NM, Bateson R, Tripathy M, et al. HIV-1 expression within resting CD4 T cells after multiple doses of vorinostat. J Infect Dis. 2014;210(5):728-735. doi:10.1093/infdis/jiu155
- Archin NM, Kirchherr JL, Sung JAM, et al. Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency. J Clin Invest. 127(8):3126-3135. doi:10.1172/JCI92684
- Kroon E, Ananworanich J, Eubanks K, et al. Effect of vorinostat, hydroxychloroquine and maraviroc combination therapy on viremia following treatment interruption in individuals treated during acute HIV infection. 21st International AIDS Conference (AIDS 2016); July 18-22, 2016; Durban, South Africa. Mascolini: Vorinostat, HCQ, Maraviroc Do Not Delay Time to Rebound After Interruption. Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2016. http://www.natap.org/2016/IAC/IAC_07.htm. Accessed May 29, 2020
- Kroon E, Ananworanich J, Le LT, et al. Central nervous system impact of vorinostat, hydroxychloroquine and maraviroc combination therapy followed by treatment interruption in individuals treated during acute HIV infection (SEARCH 026). Poster presented at: International AIDS Conference (AIDS 2016); July 18-22, 2016; Durban, South Africa. Poster LBPE005. http://programme.aids2016.org/PAGMaterial/eposters/0_10588.pdf. Accessed May 29, 2020
- Mota TM, Rasmussen TA, Rhodes A, et al. No adverse safety or virological changes 2 years following vorinostat in HIV-infected individuals on antiretroviral therapy. AIDS. 2017;31(8):1137-1141. doi:10.1097/QAD.0000000000001442
- Fidler S. RIVER research in viral eradication of HIV reservoirs: a two-arm (proof of concept) randomised Phase II trial vorinostat plus a prime boost vaccine. Slides presented at: International AIDS Conference (AIDS 2018): July 23-27, 2018; Amsterdam, the Netherlands. https://programme.aids2018.org/PAGMaterial/PPT/6106_3214/RIVER presentation at IAS 24.7.2018 final draft.pptx. Accessed May 29, 2020
- Fidler S, Stohr W, Pace M, et al. A randomised controlled trial comparing the impact of antiretroviral therapy (ART) with a “Kick-and-Kill” approach to ART alone on HIV reservoirs in individuals with primary HIV infection (PHI); RIVER trial. Abstract presented at: International AIDS Conference (AIDS 2018); July 23-27, 2018; Amsterdam, the Netherlands. Abstract TUAA0202LB. http://programme.aids2018.org/Abstract/Abstract/12977. Accessed May 29, 2020
- Scully E, Tsibris A, Aga E, et al. Effect of tamoxifen on vorinostat-induced HIV RNA expression in women on ART (ACTG A5366): the MOXIE trial. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 8-11, 2020; Boston, MA. Poster 333. https://www.croiconference.org/wp-content/uploads/sites/2/posters/2020/1430_1_Scully_00333.pdf. Accessed May 29, 2020
Last Reviewed: May 29, 2020