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.4,5
Topical microbicides can also be referred to as topical pre-exposure prophylaxis (PrEP) products.4,5 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).5,6 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.4
Dapivirine works by preventing HIV infection from spreading to other cells. It belongs to a class (group) of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).5 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.7,8 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 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.11
- 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.11
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 IV trials to seek more information about the drug’s risks, benefits, and optimal use. 11
In what phase of testing is dapivirine?
Dapivirine vaginal ring is currently being studied in Phase III clinical trials.2
What have recent studies shown about dapivirine?
In a Phase I/II study conducted in Africa (known as IPM 015), dapivirine vaginal ring was compared to placebo in HIV-uninfected women over a 12-week period. (A placebo is an inactive drug or intervention that is identical in appearance to the active drug or intervention being studied.) Study participants were instructed to insert one vaginal ring every 28 days. The purpose of this study was to investigate the safety and acceptability of the dapivirine vaginal ring. (Acceptability refers to whether study participants reported that they were likely to use the product in the future.) The study also measured how much dapivirine was absorbed throughout the body and assessed whether participants used the vaginal ring exactly as prescribed (also called adherence). This study was not designed to evaluate efficacy or how well the dapivirine vaginal ring works in preventing the sexual transmission of HIV.12,13
In the above study, 97% of the women reported that the vaginal ring was comfortable to wear, and 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 study participants reporting that the ring was either never removed or never out for more than a day. Among those women who reported that the vaginal ring had come out, the most common associated 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.13
Two ongoing studies, a Phase II/III study (known as the Ring study) and a Phase III study (known as the ASPIRE study), will evaluate how well the dapivirine vaginal ring works in protecting women against the sexual transmission of HIV.9,10,14
A vaginal ring containing both dapivirine and the FDA-approved HIV medicine maraviroc (brand name: Selzentry) has been studied in a Phase I clinical trial.15 Other forms of dapivirine-containing microbicides are also being studied, including a vaginal gel and a vaginal film.7,8
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.13
Because dapivirine is still being studied, information on possible side effects of the drug is not complete. As testing of dapivirine 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.11
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.
1. United States National Library of Medicine. ChemIDplus Advanced. Last accessed on January 8, 2014.
2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Last accessed on January 8, 2014.
3. International Partnership for Microbicides (IPM) website. IPM Product Pipeline: Dapivirine. Last accessed on January 8, 2014.
4. National Institute of Allergy and Infectious Diseases (NIAID). Topical Microbicides. Last accessed on January 8, 2014.
5. Shattock RJ, Rosenberg Z. Microbicides: Topical Prevention against HIV. Cold Spring Harb Perspect Med. 2012 Feb;2(2):a007385. Last accessed on January 8, 2014.
6. 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. Last accessed on January 8, 2014.
7. Adams JL, Kashuba AD. Formulation, pharmacokinetics and pharmacodynamics of topical microbicides. Best Pract Res Clin Obstet Gynaecol. 2012 Aug;26(4):451-62. Last accessed on January 8, 2014.
8. International Partnership for Microbicides, Inc. Assessing the Safety of Dapivirine Gel and Film Formulations. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2012. NLM Identifier: NCT01548560. Last accessed on January 8, 2014.
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. Last accessed on January 8, 2014.
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. Last accessed on January 8, 2014.
11. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Last accessed on January 8, 2014.
12. 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. Last accessed on January 8, 2014.
13. 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. Last accessed on January 8, 2014.
14. International Partnership for Microbicides (IPM): Press Releases and Statements, dated June 13, 2012. First Efficacy Trial of a Microbicide Ring to Prevent HIV Is Underway. Last accessed on January 8, 2014.
15. 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. Last accessed on January 8, 2014.
Last Reviewed: January 8, 2014
Last Updated: January 8, 2014