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AIDSinfo Drug Database

AIDSinfo Drug Database

Drugs by class

FDA-approved

Investigational

Dapivirine  Audio icon

Other Names: DAP, 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
Company: Janssen Research and Development, LLC; International Partnership for Microbicides (IPM)
Phase of Development: Phase III (Dapivirine intravaginal ring [IVR] is in Phase III testing. Other dapivirine-based microbicide products are in earlier phases of study.)
Chemical Image:
Click image to enlarge
dapivirine
dapivirine
Molecular Weight: 329.405
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 International Partnership for Microbicides [IPM] press release,3 and IPM's Next Generation Products presentation4)

What is an investigational drug?

An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.

What is dapivirine?

Dapivirine is an investigational drug that is being studied to prevent sexual transmission of HIV. It is a type of drug product called a topical microbicide. Topical microbicides are products that are applied to the vagina or rectum (such as gels, films, or creams) or inserted into the vagina (such as vaginal rings) to prevent getting sexually transmitted infections, such as HIV infection.5,6

Dapivirine belongs to a class (group) of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).6 NNRTIs attach to and block an HIV enzyme called reverse transcriptase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking reverse transcriptase, NNRTIs prevent HIV from multiplying and from spreading to other cells.

Several different forms of dapivirine-based microbicide products are being studied, including a vaginal ring (also known as an intravaginal ring or IVR), a vaginal gel, and a vaginal film.8-11 The dapivirine vaginal ring is furthest along in development.9,10 It provides long-term delivery of dapivirine over a period of 4 weeks.9

How do topical microbicides work?

Topical microbicides can also be referred to as topical pre-exposure prophylaxis (PrEP) products.5,6 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.

Topical microbicides to prevent HIV infection are designed to work close to where they are applied and near to where HIV might enter the body (through the vagina or rectum).6,7 They may prevent HIV transmission in a number of ways. For example, HIV topical microbicides might:

  • inactivate HIV or other pathogens (also called disease-causing microorganisms);
  • strengthen the body’s normal defenses;
  • block HIV from attaching to healthy cells susceptible to infection;
  • prevent HIV infection from spreading to other cells that are healthy.5

Dapivirine works by preventing HIV infection from spreading to other cells.6

How are clinical trials of investigational drugs conducted?

Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.12

  • Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
  • Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
  • Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.12
In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IVtrials to seek more information about the drug’s risks, benefits, and optimal use.12
 

In what phase of testing is dapivirine?

Dapivirine vaginal ring is currently being studied in Phase III clinical trials.2,4

Other dapivirine-based microbicides are in Phase I and II studies. These include a combination antiretroviral vaginal ring containing dapivirine and the FDA-approved HIV medicine maraviroc (brand name: Selzentry), a vaginal gel, and a vaginal film.4

 

What are some studies on dapivirine?

Dapivirine Vaginal Ring:

Study Name: IMP 015
Phase: I/II
Location: Africa
Participants: Healthy, HIV-uninfected women
Purpose: To look at the safety and acceptability of dapivirine vaginal ring. (Acceptability refers to whether study participants reported that they were likely to use the product in the future.)
Study Design: Participants were randomly assigned to use either dapivirine vaginal ring or a placebo ring. (A placebo is an inactive drug or intervention that is identical in appearance to the active drug or intervention being studied.) Both groups of participants were instructed to insert one vaginal ring every 28 days over a 12-week period. Researchers also measured how much dapivirine was absorbed throughout the body and assessed whether participants used the vaginal ring exactly as prescribed (also called adherence). 
Results

  • 97% of the women reported that the vaginal ring was comfortable to wear. 
  • 97% of the women reported that they were willing to use the vaginal ring in the future if it’s shown to be safe and effective for preventing HIV infection.
  • Adherence with using the vaginal ring was good, with 92% of participants reporting that the ring was either never removed or never out for more than a day. Among those women who said that the vaginal ring had come out, the most common reason was vaginal ring cleaning, and the most common associated activity was urination or bowel movement.
  • Participants had low levels of dapivirine in the blood, indicating low absorption of dapivirine throughout the body. 
  • In terms of safety, none of the side effects that occurred in the study were definitely related to dapivirine.
  • This study did not evaluate the efficacy or how well the dapivirine vaginal ring works in preventing sexual transmission of HIV.13,14

Study Name: IPM 027 (also known as The Ring Study)
Phase: II/III
Location: Africa
Participants: HIV-uninfected women
Purpose: To evaluate whether a dapivirine vaginal ring is safe and effective in protecting women against sexually acquired HIV
Study Design: Participants are randomly assigned to use either a monthly dapivirine vaginal ring or a placebo ring. Participants are instructed on how to insert one new vaginal ring after removing the used ring each month. Participation in this study will be for 2 years.9,15
* The Ring Study is currently ongoing and results are not yet available.

Study Name: MTN-020 (also known as ASPIRE)
Phase: III
Location: Africa
Participants: HIV-uninfected women
Purpose: To evaluate whether a dapivirine vaginal ring is safe and effective in protecting women against sexually acquired HIV
Study Design: Participants are randomly assigned to use either a monthly dapivirine vaginal ring or a placebo ring. Participants are instructed on how to insert one new vaginal ring after removing the used ring each month. Participation in this study will be for at least 1 year.10,15
* ASPIRE is currently ongoing and results are not yet available.

Other dapivirine vaginal ring trials have either been completed or are ongoing or planned. 

What side effects might dapivirine cause?

In the Phase I/II IPM 015 study discussed under the previous question, none of the reported side effects were considered definitely related to use of the dapivirine vaginal ring. Side effects in the dapivirine and placebo groups were similar.14

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

 

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.

 

I am interested in participating in a clinical trial of dapivirine. How can I find more information about participating in a clinical trial?

Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.12

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

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/244767-67-7. Last accessed on April 1, 2015.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on April 1, 2015.
  3. International Partnership for Microbicides (IPM): Press Release, dated May 8, 2014. IPM Receives Worldwide Rights to HIV Prevention Medicine. Available at: http://ipmglobal.org/publications/ipm-receives-worldwide-rights-hiv-prevention-medicine. Last accessed on April 1, 2015.
  4. Rosenberg Z. IPM’s Next Generation Products. Slides presented at: Microbicide Trials Network (MTN) 2014 Annual Meeting; February 23-26, 2014; Bethesda, Maryland. Available at: http://www.mtnstopshiv.org/sites/default/files/attachments/ROSENBERG-MTNPlenary_Z%20Rosenberg-24FEB14.pdf. Last accessed on April 1, 2015.
  5. National Institute of Allergy and Infectious Diseases (NIAID). Topical Microbicides. Available at: http://www.niaid.nih.gov/topics/hivaids/research/prevention/pages/topicalmicrobicides.aspx. Last accessed on April 1, 2015.
  6. Shattock RJ, Rosenberg Z. Microbicides: Topical Prevention against HIV. Cold Spring Harb Perspect Med. 2012 Feb;2(2):a007385. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281595/. Last accessed on April 1, 2015.
  7. Cranage M, Sharpe S, Herrera C, et al. Prevention of SIV Rectal Transmission and Priming of T Cell Responses in Macaques after Local Pre-exposure Application of Tenofovir Gel. PLoS Med. 2008 Aug 5;5(8):e157; discussion e157. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2494562/. Last accessed on April 1, 2015.
  8. Adams JL, Kashuba AD. Formulation, pharmacokinetics and pharmacodynamics of topical microbicides. Best Pract Res Clin Obstet Gynaecol. 2012 Aug;26(4):451-62. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662244/. Last accessed on April 1, 2015.
  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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01539226. Last accessed on April 1, 2015.
  10. 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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01617096. Last accessed on April 1, 2015.
  11. International Partnership for Microbicides, Inc. Comparison of the Pharmacokinetics and Pharmacodynamics of Single Dose Dapivirine Vaginal Gel and Film Formulation. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 13, 2013. NLM Identifier: NCT01924091. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01924091. Last accessed on April 1, 2015.
  12. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://nih.gov/health/clinicaltrials/index.htm. Last accessed on April 1, 2015.
  13. International Partnership for Microbicides, Inc. A Double-Blind, Randomized, Placebo-Controlled Phase I/II Study to Evaluate the Safety of an Intravaginal Matrix Ring With Dapivirine in Healthy, HIV-Negative Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 17, 2010. NLM Identifier: NCT01071174. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01071174. Last accessed on April 1, 2015.
  14. Nel A, Kamupira M, Woodsong C, et al. Safety, Acceptibility and Pharmacokinetic Assessment (Adherence) of Monthly Dapivirine Vaginal Microbicide Rings (Ring-004) for HIV Prevention. 19th Conference on Retroviruses and Opportunistic Infections (CROI); March 5-8, 2012; Seattle, WA. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2012. Available at: http://www.natap.org/2012/CROI/croi_160.htm. Last accessed on April 1, 2015.
  15. International Partnership for Microbicides (IPM) website. Two Phase III Sister Studies of a Microbicide Ring to Prevent HIV: The Ring Study & ASPIRE. Available at: http://www.ipmglobal.org/node/668. Last accessed on April 1, 2015.
 


Last Reviewed: April 1, 2015

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