Drugs

Dapivirine

Dapivirine

Other Names: DAP, DPV, DVR, DVR-004, 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 Sciences Ireland UC; International Partnership for Microbicides (IPM) Phase of Development: The monthly dapivirine intravaginal ring has completed Phase IIIb testing, and is currently being reviewed by the European Medicines Agency (EMA). The drug sponsor plans to seek approval for the dapivirine ring from the U.S. Food and Drug Administration and the South African Health Products Regulatory Authority in 2019. 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] publication,3 and IPM website4)

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.5,6 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).6 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.5,6 Several different forms of dapivirine-based microbicide products are being studied, including gels, vaginal rings, and a vaginal film.4

Topical microbicides may also be called topical pre-exposure prophylaxis (PrEP) products.6 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?

Dapivirine Vaginal Ring

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 was a follow-up Phase IIIb trial.
Status: The Ring and DREAM studies have both been completed.
Locations: South Africa and Uganda
Purpose: The purpose of the Ring study was to evaluate whether a monthly dapivirine vaginal ring was safe and effective in protecting women against sexually acquired HIV. The DREAM study continued to evaluate the safety of the dapivirine vaginal ring. The DREAM study also looked at how well participants followed the study instructions for using the vaginal ring.7,8

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 was a Phase IIIb follow-up trial.
Status: The ASPIRE and HOPE studies have both been completed.
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 continued to evaluate the safety of the dapivirine vaginal ring. The HOPE study also looked at how well participants followed the study instructions for using the vaginal ring.9,10

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

Additional dapivirine vaginal ring studies include:
  • MTN-036/IPM 047 (NCT03234400): A completed Phase I study that compared the safety and pharmacokinetics of three vaginal rings that contained different amounts of dapivirine.11
  • MTN-044/IPM 053/CCN019 (NCT03467347): A Phase I study evaluating the pharmacokinetics and safety of a vaginal ring that contains both dapivirine and levonorgestrel. This study is currently recruiting participants.12
  • REACH; MTN-034 (NCT03593655): A Phase IIa study of adolescent and young adult female participants that is evaluating the safety of and adherence to the monthly dapivirine vaginal ring and emtricitabine/tenofovir disoproxil fumarate taken by mouth. This study is currently recruiting participants.13,14

Other Dapivirine-Based Microbicides

Other dapivirine-based microbicides are also being studied, including a vaginal film (Phase I) and a gel that is used inside the rectum (Phase I) or vagina (Phase II). A vaginal gel that contains dapivirine and darunavir has also been studied in a Phase I trial.4,15,16

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.7,17 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.7,17

DREAM Study (NCT02862171):
Interim results from the DREAM study showed that only three 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.18

ASPIRE Study (NCT01617096):
In the ASPIRE study, use of the dapivirine ring was 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.17,19,20 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.21

Because the dapivirine vaginal ring is still being studied, information on possible side effects of this 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 May 8, 2019.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed May 8, 2019.
  3. International Partnership for Microbicides (IPM). A long-acting ring to help protect women against HIV. https://www.ipmglobal.org/sites/default/files/media_block_files/ring_backgrounder_-_feb_2019.pdf. Accessed May 8, 2019.
  4. International Partnership for Microbicides (IPM) website. Our products. https://www.ipmglobal.org/our-work/product-pipeline. Accessed May 8, 2019.
  5. National Institute of Allergy and Infectious Diseases (NIAID). Microbicides to block transmission of HIV. https://www.niaid.nih.gov/diseases-conditions/microbicides. Accessed May 8, 2019.
  6. Shattock RJ, Rosenberg Z. Microbicides: topical prevention against HIV. Cold Spring Harb Perspect Med. 2012;2(2):a007385.
  7. 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 May 8, 2019.
  8. 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 May 8, 2019.
  9. 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 May 8, 2019.
  10. 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 May 8, 2019.
  11. International Partnership for Microbicides, Inc. A Phase 1, randomized pharmacokinetics and safety study of extended duration dapivirine vaginal rings. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 25, 2017. NLM Identifier: NCT03234400. https://clinicaltrials.gov/ct2/show/NCT03234400. Accessed May 8, 2019.
  12. International Partnership for Microbicides, Inc. A randomized, Phase 1, open-label study in healthy HIV-negative women to evaluate the pharmacokinetics, safety and bleeding patterns associated with 90-day use of matrix vaginal rings containing 200 mg dapivirine and 320 mg levonorgestrel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 9, 2018. NLM Identifier: NCT03467347. https://clinicaltrials.gov/ct2/show/NCT03467347. Accessed May 8, 2019.
  13. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 2a crossover trial evaluating the safety of and adherence to a vaginal matrix ring containing dapivirine and oral emtricitabine/tenofovir disoproxil fumarate in an adolescent and young adult female population. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 10, 2018. NLM Identifier: NCT03593655. https://clinicaltrials.gov/ct2/show/NCT03593655. Accessed May 8, 2019.
  14. Microbicide Trials Network (MTN): Press Release, dated February 7, 2019. About the REACH Study (MTN-034). https://mtnstopshiv.org/news/about-reach-study-mtn-034. Accessed May 8, 2019.
  15. International Partnership for Microbicides (IPM) website. Darunavir. https://www.ipmglobal.org/our-work/arvs-in-the-pipeline/darunavir. Accessed May 8, 2019.
  16. National Institute of Allergy and Infectious Diseases (NIAID). An Open Label Randomized Phase 1 Pharmacokinetic Study of Dapivirine Gel Administered Rectally to HIV-1 Seronegative Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 2, 2018. NLM Identifier: NCT03393468. https://clinicaltrials.gov/ct2/show/NCT03393468. Accessed May 8, 2019.
  17. 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
  18. 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 May 8, 2019.
  19. International Partnership for Microbicides (IPM): Press Release, dated February 22, 2016. Two large studies show IPM’s monthly vaginal ring helps protect women against HIV. https://www.ipmglobal.org/publications/two-large-studies-show-ipm%E2%80%99s-monthly-vaginal-ring-helps-protect-women-against-hiv. Accessed May 8, 2019.
  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
  21. Baeten J. High uptake and reduced HIV-1 incidence in an open-label trial of the dapivirine ring. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2018; Boston, MA. http://www.croiwebcasts.org/console/player/37318?mediaType=slideVideo&&crd_fl=1&ssmsrq=1521029770826&ctms=5000&csmsrq=780. Accessed May 8, 2019.

Last Reviewed: May 8, 2019