Drug information

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Pronounce:
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 3b 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. 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?

What is dapivirine?

 

Dapivirine is an investigational drug that is being studied as a topical microbicide to prevent sexual transmission of HIV.5,6

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.

To learn about how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

How do topical microbicides work?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 intravaginal rings or IVRs). 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 Researchers have studied several different dapivirine-based microbicide products, 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 HIVinfo Pre-Exposure Prophylaxis (PrEP) fact sheet.

Which clinical trials are studying dapivirine?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 3 trial, and the DREAM study was a follow-up Phase 3b 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 3 trial, and the HOPE study was a Phase 3b 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 1 study that evaluated dapivirine vaginal rings that can be used for an extended period of time.11
  • MTN-044/IPM 053/CCN019 (NCT03467347): A completed Phase 1 study that evaluated the pharmacokinetics and safety of a vaginal ring that contained both dapivirine and levonorgestrel.12
  • REACH; MTN-034 (NCT03593655): A Phase 2a study of adolescent and young adult female participants that is evaluating the safety of and adherence to the monthly dapivirine vaginal ring and oral emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada). This study is currently recruiting participants.13,14
  • MTN-042 (NCT03965923): A Phase 3b study evaluating the safety of the dapivirine IVR and oral Truvada when used during pregnancy. This study is currently recruiting participants.15
  • MTN-043 (NCT04140266): A Phase 3b trial assessing the safety and drug detection of the dapivirine IVR and Truvada in breastfeeding mother-infant pairs. See the ClinicalTrials.gov record for this study’s status.16
     

Other Dapivirine-Based Microbicides
 

Other dapivirine-based microbicides have been studied, including a vaginal film (Phase 1) and a gel that is used inside the rectum (Phase 1) or vagina (Phase 2). A vaginal gel that contains both dapivirine and darunavir has also been studied in a Phase 1 trial.4,17,18

What side effects might dapivirine cause?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 3 study, the dapivirine ring was reported to be safe, with no difference in safety concerns between the dapivirine ring group and the placebo group. 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.7,19

DREAM Study (NCT02862171):
In this follow-on study to the Ring trial, the dapivirine ring was found to have a similar safety profile to what has been seen in Phase 3 studies. Among 941 participants who enrolled in the DREAM study, 66% of participants experienced a side effect. A little under half of the enrolled participants reported having a genitourinary tract side effect, the most common of which were chlamydia infection, gynecological infection, and inflammation of the vulva and vagina. Serious side effects occurred in 2% of participants. Only six participants experienced a side effect that was related to the study product.8,20

ASPIRE Study (NCT01617096):
In this Phase 3 study, the 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.19,21,22 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.22

HOPE Study (NCT02858037):
The follow-on HOPE study demonstrated a safety profile similar to that of the ASPIRE study. Among 1,456 participants who enrolled in the study, no serious or severe side effects related to dapivirine occurred. Moderate side effects related to dapivirine occurred in just two participants.10,23

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?

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

More information about dapivirine-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 clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

ReferencesReferences

References

 

  1. United States National Library of Medicine. ChemIDplus advanced: Dapivirine. https://chem.nlm.nih.gov/chemidplus/rn/244767-67-7. Accessed February 10, 2020
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed February 10, 2020
  3. International Partnership for Microbicides (IPM). A long-acting ring to help women protect themselves against HIV. Accessed February 10, 2020
  4. International Partnership for Microbicides (IPM) website. Our products. https://www.ipmglobal.org/our-work/product-pipeline. Accessed February 10, 2020
  5. National Institute of Allergy and Infectious Diseases (NIAID). Microbicides to block transmission of HIV. https://www.niaid.nih.gov/diseases-conditions/microbicides. Accessed February 10, 2020
  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 February 10, 2020
  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 February 10, 2020
  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 February 10, 2020
  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 February 10, 2020
  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 February 10, 2020
  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 February 10, 2020
  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 February 10, 2020
  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 February 10, 2020
  15. National Institute of Allergy and Infectious Diseases (NIAID). Phase 3b, randomized, open label safety trial of dapivirine vaginal ring and oral Truvada® use in pregnancy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 24, 2019. NLM Identifier: NCT03965923. https://clinicaltrials.gov/ct2/show/NCT03965923. Accessed February 10, 2020
  16. National Institute of Allergy and Infectious Diseases (NIAID). Phase 3B, randomized, open-label, safety, and drug detection study of dapivirine vaginal ring and oral Truvada® in breastfeeding mother-infant pairs. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 24, 2019. NLM Identifier: NCT04140266. https://clinicaltrials.gov/ct2/show/NCT04140266. Accessed February 10, 2020
  17. International Partnership for Microbicides (IPM) website. Darunavir. https://www.ipmglobal.org/our-work/arvs-in-the-pipeline/darunavir. Accessed February 10, 2020
  18. 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 February 10, 2020
  19. 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
  20. Nel A. Safety, adherence and HIV-1 seroconversion in DREAM – an open-label dapivirine vaginal ring trial. Slides presented at: SA AIDS Conference; June 11-14, 2019; Durban, South Africa. https://www.saaids.co.za/.cm4all/uproc.php/0/Hall 1/Hall 1/Dr Annalene Nel.pdf?cdp = a&_=16bd6bf1740. Accessed February 10, 2020
  21. 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’s-monthly-vaginal-ring-helps-protect-women-against-hiv. Accessed February 10, 2020
  22. 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
  23. Baeten J, Palanee-Phillips T, Mgodi N, et al. High adherence and sustained impact on HIV-1 incidence: final results of an open-label extension trial of the dapivirine ring. Slides presented at: International AIDS Society (IAS) Conference on HIV Science; July 21-24, 2019; Mexico City, Mexico. http://programme.ias2019.org/PAGMaterial/PPT/1114_3329/MTN-025 HOPE - IAS 2019 presentation -- version20190718final.pptx. Accessed February 10, 2020
 

Last Reviewed: February 10, 2020