Drugs

Dapivirine

Dapivirine

Other Names: DAP, DPV, Ring-004, TMC-120, dapivirine IVR, dapivirine intravaginal ring Drug Class: Microbicides Molecular Formula: C20 H19 N5 Registry Number: 244767-67-7 (CAS) Chemical Name: 4-[[4-(2,4,6-trimethylanilino)pyrimidin-2-yl]amino]benzonitrile Chemical Class: Pyrimidines Organization: Janssen Research and Development, LLC; International Partnership for Microbicides (IPM) Phase of Development: The dapivirine intravaginal ring is in Phase IIIb testing. An application for the dapivirine ring is under review by the European Medicines Agency (EMA). The drug sponsor also plans to seek approval for the dapivirine ring from the U.S. Food and Drug Administration and the South African Health Products Regulatory Authority. Other dapivirine-based microbicide products are in earlier phases of study.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 International Partnership for Microbicides [IPM] press releases,3-5 and IPM website6)

What is dapivirine?

What is dapivirine?

Dapivirine is an investigational drug that is being studied as a topical microbicide to prevent sexual transmission of HIV.7,8 To learn more about how investigational drugs are tested during clinical trials, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

Dapivirine belongs to a group of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).8 NNRTIs attach to and block an HIV enzyme called reverse transcriptase.

How do topical microbicides work?

How do topical microbicides work?

Topical microbicides come in many different forms, including gels, creams, films, and vaginal rings (also called an intravaginal ring or IVR). These products are designed to prevent HIV infection during sex, so they are used close to where HIV might enter the body during sexual activities—either the vagina or rectum.7,8 Several different forms of dapivirine-based microbicide products are being studied, including gels, vaginal rings, and a vaginal film.6

Topical microbicides may also be called topical pre-exposure prophylaxis (PrEP) products.8 PrEP means using a medicine before possible exposure to a virus or bacteria to reduce the risk of becoming infected with the virus or bacteria. For more information on PrEP, see the AIDSinfo Pre-Exposure Prophylaxis (PrEP) fact sheet.

Which clinical trials are studying dapivirine?

Which clinical trials are studying dapivirine?

Study Names: (1) Ring Study; IPM 027; NCT01539226 and (2) DREAM Study; IPM 032; NCT02862171
Phase: The Ring study was a Phase III trial, and the DREAM study is a follow-on Phase IIIb trial.
Status: The Ring study has been completed. The DREAM study is currently recruiting participants.
Locations: South Africa and Uganda
Purpose: The purpose of the Ring study was to evaluate whether a dapivirine vaginal ring was safe and effective in protecting women against sexually acquired HIV. The DREAM study is a follow-on study to continue evaluating the safety of the dapivirine vaginal ring. The DREAM study is also looking at how well participants follow the study instructions for using the vaginal ring.9-12

Study Names: (1) ASPIRE Study; MTN-020; NCT01617096 and (2) HOPE Study; MTN-025; NCT02858037
Phase: The ASPIRE study was a Phase III trial, and the HOPE study is a Phase IIIb follow-on trial.
Status: The ASPIRE study has been completed. The HOPE study is currently recruiting participants.
Locations: Malawi, South Africa, Uganda, and Zimbabwe
Purpose: The purpose of the ASPIRE study was to evaluate whether a dapivirine vaginal ring was safe and effective in protecting women against sexually acquired HIV. The HOPE study is an ongoing study that continues to evaluate the safety of the dapivirine vaginal ring. The HOPE study also looks at how well participants follow the study instructions for using the vaginal ring.13,14

For more details on the studies listed above, see the Health Professional version of this drug summary.

Additional dapivirine vaginal ring studies have been completed, including the following:

  • MTN-030/IPM 041 (NCT02855346), a Phase I study that evaluated a combination IVR containing dapivirine and levonorgestrel15
  • MTN-013/IPM 026 (NCT01363037), a Phase I study that evaluated a combination IVR containing dapivirine and maraviroc16
  • MTN-023/IPM 030 (NCT02028338), a Phase IIa study that evaluated the safety of the dapivirine IVR in adolescent females17

 

What side effects might dapivirine cause?

What side effects might dapivirine 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 dapivirine listed above.

Ring Study (NCT01539226):
In this Phase III study, the dapivirine ring was reported to be safe, with no difference in safety concerns between the dapivirine ring group and the placebo group.9,18 In the study, some side effects related to the dapivirine ring included abnormal uterine bleeding, pelvic discomfort or pain, lower abdominal (suprapubic) pain, and pain where the ring was located. All of these side effects were mild in severity.9,18

DREAM Study (NCT02862171):
Interim results from the follow-on DREAM study reported that only 3 participants had a side effect related to the dapivirine ring. These side effects were lower abdominal pain, inflammation or infection of the vulva and vagina, and pain in the vulvar and vaginal areas.19

ASPIRE Study (NCT01617096):
In the ASPIRE study, use of the dapivirine ring was also reported to be safe. Similar to the Ring study, there was no difference in the occurrence of side effects between the dapivirine ring group and the placebo group.18,21 In the study, side effects related to the dapivirine ring included inflammation, reddening, or swelling of the cervix; urinary tract infection; loss of bladder control; headache; pain during sex; and pelvic pain.20

Because the dapivirine vaginal ring is still being studied, information on possible side effects of the drug product is not complete. As testing of the dapivirine vaginal ring continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying dapivirine?

Where can I get more information about clinical trials studying dapivirine?

More information about dapivirine-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus advanced: Dapivirine. https://chem.nlm.nih.gov/chemidplus/rn/244767-67-7. Accessed August 17, 2018.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed August 17, 2018.
  3. International Partnership for Microbicides (IPM): Press Release, dated May 8, 2014. IPM receives worldwide rights to HIV prevention medicine. https://www.ipmglobal.org/publications/ipm-receives-worldwide-rights-hiv-prevention-medicine. Published May 8, 2014. Accessed August 17, 2018.
  4. International Partnership for Microbicides (IPM): Press Release, dated March 6, 2018. Interim results of open-label study of IPM’s dapivirine vaginal ring find increased product use and suggest greater HIV risk reduction. https://www.ipmglobal.org/content/interim-results-open-label-study-ipm%E2%80%99s-dapivirine-vaginal-ring-find-increased-product-use. Published March 5, 2018. Accessed August 17, 2018.
  5. International Partnership for Microbicides (IPM): Press Release, dated July 13, 2017. IPM’s application for dapivirine vaginal ring for reducing HIV risk in women now under review by European Medicines Agency. https://www.ipmglobal.org/content/ipm%E2%80%99s-application-dapivirine-vaginal-ring-reducing-hiv-risk-women-now-under-review-european. Published July 12, 2017. Accessed August 17, 2018.
  6. International Partnership for Microbicides (IPM) website. Product pipeline. https://www.ipmglobal.org/our-work/product-pipeline. Published March 3, 2016. Accessed August 17, 2018.
  7. National Institute of Allergy and Infectious Diseases (NIAID). Microbicides to block transmission of HIV. https://www.niaid.nih.gov/diseases-conditions/microbicides. Accessed August 17, 2018.
  8. Shattock RJ, Rosenberg Z. Microbicides: Topical prevention against HIV. Cold Spring Harb Perspect Med. 2012;2(2):a007385.
  9. International Partnership for Microbicides, Inc. A multi-centre, randomised, double-blind, placebo-controlled safety and efficacy trial of a dapivirine vaginal matrix ring in healthy HIV-negative women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 21, 2012. NLM Identifier: NCT01539226. https://clinicaltrials.gov/ct2/show/NCT01539226. Accessed August 17, 2018.
  10. Rosenberg Z. Dapivirine ring: the roadmap to licensure. Slides presented at: MTN Regional Meeting; October 4-8, 2015; Cape Town, South Africa. http://www.mtnstopshiv.org/sites/default/files/attachments/ROSENBERG2015-10-MTN-regional-mtg-Zeda_draftSept29.pdf. Accessed August 17, 2018.
  11. International Partnership for Microbicides, Inc. A follow-on, open-label trial to assess continued safety of and adherence to the dapivirine (25 mg) vaginal Ring-004 in healthy, HIV-negative women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 25, 2016. NLM Identifier: NCT02862171. https://clinicaltrials.gov/ct2/show/NCT02862171. Accessed August 17, 2018.
  12. International Partnership for Microbicides (IPM) website. IPM 032 (DREAM). https://www.ipmglobal.org/content/ipm-032-dream. Published July 7, 2016. Accessed August 17, 2018.
  13. International Partnership for Microbicides, Inc. A multi-center, randomized, double-blind, placebo-controlled Phase 3 safety and effectiveness trial of a vaginal matrix ring containing dapivirine for the prevention of HIV-1 infection in women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 8, 2012. NLM Identifier: NCT01617096. https://clinicaltrials.gov/ct2/show/NCT01617096. Accessed August 17, 2018.
  14. International Partnership for Microbicides, Inc. A Phase 3B open-label follow-on trial to assess the continued safety of and adherence to a vaginal ring containing dapivirine in women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 18, 2016. NLM Identifier: NCT02858037. https://clinicaltrials.gov/ct2/show/NCT02858037. Accessed August 17, 2018.
  15. International Partnership for Microbicides, Inc. A Phase 1, randomized, double-blind pharmacokinetic and safety study of dapivirine/levonorgestrel vaginal rings. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 21, 2016. NLM Identifier: NCT02855346. https://clinicaltrials.gov/ct2/show/NCT02855346. Accessed August 17, 2018.
  16. International Partnership for Microbicides, Inc. Phase 1 safety and pharmacokinetics of dapivirine/maraviroc vaginal ring. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 27, 2011. NLM Identifier: NCT01363037. https://clinicaltrials.gov/ct2/show/NCT01363037. Accessed August 17, 2018.
  17. International Partnership for Microbicides, Inc. Phase 2a study of a vaginal ring containing dapivirine in adolescent females. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 2, 2014. NLM Identifier: NCT02028338. https://clinicaltrials.gov/ct2/show/record/NCT02028338. Accessed August 17, 2018.
  18. Nel A, van Niekerk N, Kapiga S, et al. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N Engl J Med. 2016;375(22):2133-2143. doi:10.1056/NEJMoa1602046
  19. Rosenberg ZF. HIV Incidence and adherence in DREAM - an open-label trial of dapivirine vaginal ring. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2018; Boston, MA. http://www.croiwebcasts.org/console/player/37319?mediaType=slideVideo&&crd_fl=0&ssmsrq=1525645233234&ctms=5000&csmsrq=5001. Accessed August 17, 2018.
  20. Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med. 2016;375(22):2121-2132. doi:10.1056/NEJMoa1506110

Last Reviewed: August 17, 2018