NOTE: The development of PRO-2000 for preventing sexually acquired HIV infection has been discontinued.
The study of PRO-2000 as a microbicide for preventing HIV infection was discontinued in 2009. Data from a Phase III study showed that PRO-2000 vaginal gel was ineffective in protecting women against sexually acquired HIV infection.4
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 PRO-2000?
PRO-2000 is an investigational drug that has been studied to prevent sexual transmission of HIV and other sexually transmitted infections (STIs).5 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 STIs, such as HIV infection.6
PRO-2000 belongs to a group of drugs called polyanion-based entry inhibitors.7 Polyanion-based entry inhibitors interact through an electrostatic association with the surface of viruses such as HIV. The interaction between the negatively charged surface of a polyanion-based entry inhibitor and HIV’s positively charged surface may prevent HIV from attaching to, entering, or infecting healthy cells.8-10
PRO-2000 is currently in a gel form. The gel has been studied for vaginal use.11,12
How do topical microbicides work?
Topical microbicides can also be referred to as topical pre-exposure prophylaxis (PrEP) products.6,13 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).13,14 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.6
PRO-2000 works by blocking HIV from attaching to susceptible, healthy cells.15
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.16
- 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.16
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.16
In what phase of testing is PRO-2000?
PRO-2000 vaginal gel has been studied in a Phase III clinical trial.2
The development of PRO-2000 vaginal gel for preventing HIV infection has since been discontinued.4
What are some studies on PRO-2000?
Study Name: HPTN 035
Location: Africa and United States
Participants: HIV-uninfected women
Purpose: To look at the safety and effectiveness of two different investigational microbicide gels—Carbopol 974P (brand name: BufferGel) and PRO-2000—for preventing sexually acquired HIV infection in women.
Study Design: Participants were randomly assigned to use BufferGel, PRO-2000 gel, a placebo gel, or no gel at all. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) Participants who were assigned to a gel group were instructed to apply the gel vaginally within 1 hour of having vaginal intercourse. Women used the gels for approximately 20 months.
- PRO-2000 vaginal gel was found to be about 30% effective in protecting HIV-uninfected women from acquiring HIV. This result, however, was not statistically significant, meaning that the gel’s effect may have been the result of chance rather than a true protective effect.
- BufferGel, the other investigational microbicide tested in this study, had no effect on preventing HIV infection in women.
- Both PRO-2000 vaginal gel and BufferGel were not effective in preventing other STIs (gonorrhea, chlamydia, and trichomoniasis).
- In terms of safety, both PRO-2000 and BufferGel were determined to be safe.11,17-19
Study Name: MDP 301
Participants: HIV-uninfected women
Purpose: To look at the safety and effectiveness of two different strengths of PRO-2000 vaginal gel for preventing sexually acquired HIV infection in women
Study Design: Participants were randomly assigned to use 0.5% PRO-2000 vaginal gel, 2% PRO-2000 vaginal gel, or placebo gel. Participants were instructed to apply gels vaginally within an hour before sexual intercourse. Women used the gels for approximately 52 weeks. (Women in Uganda used the gel for up to 104 weeks to provide long-term safety data.)
- Both 0.5% and 2% PRO-2000 gels were ineffective in reducing the risk of HIV infection or other STIs (herpes simplex virus type 2 [HSV-2], gonorrhea, and chlamydia).
- In terms of safety, side effects were similar in the women using PRO-2000 gel and in those using placebo gel.4,12,18,20
Note: During this study, the 2% PRO-2000 gel group was stopped early because of a low chance of showing a beneficial effect.12
What side effects might PRO-2000 cause?
In both the Phase II/IIb and Phase III studies discussed under the previous question, PRO-2000 vaginal gel was determined to be safe.11,12,18 The side effect most commonly reported by women in the MDP 301 study was genital itching.12
If testing of PRO-2000 vaginal gel continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying PRO-2000?
More information about PRO-2000-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 PRO-2000. 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.16
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.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/29321-75-3. Last accessed on May 20, 2015.
- 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 May 20, 2015.
- Endo Pharmaceuticals Inc.: News Release, dated January 5, 2009. Endo Pharmaceuticals to Acquire Indevus Pharmaceuticals. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=123046&p=irol-newsArticle_print&ID=1240465&highlight. Last accessed on May 20, 2015.
- Medical Research Council: Press Release, dated December 14, 2009. HIV ‘prevention’ gel PRO 2000 proven ineffective. Available at: http://www.mdp.mrc.ac.uk/downloads/MDP%20Microbicides%20release%20111209%20%20Embargoed%20until%20141209.pdf. Last accessed on May 20, 2015.
- Fletcher PS, Shattock RJ. PRO-2000, an antimicrobial gel for the potential prevention of HIV infection. Curr Opin Investig Drugs. 2008 Feb;9(2):189-200. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18246522. Last accessed on May 20, 2015.
- 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 May 20, 2015.
- Sachdev DD, Zerhouni-Layachi B, et al. The Differential Binding and Activity of PRO 2000 Against Diverse HIV-1 Envelopes. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):125-9. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718789/. Last accessed on May 20, 2015.
- International Partnership for Microbicides (IPM) website. Glossary: Polyanion. Available at: http://www.ipmglobal.org/our-work/glossary/polyanion. Last accessed on May 20, 2015.
- Fletcher PS, Wallace GS, Mesquita PM, Shattock RJ. Candidate polyanion microbicides inhibit HIV-1 infection and dissemination pathways in human cervical explants. Retrovirology. 2006 Aug 1;3:46. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590048/. Last accessed on May 20, 2015.
- Garg AB, Nuttall J, Romano J. The future of HIV microbicides: challenges and opportunities. Antivir Chem Chemother. 2009;19(4):143-50. Available at: http://avc.sagepub.com/content/19/4/143.long. Last accessed on May 20, 2015.
- Abdool Karim SS, Richardson BA, Ramjee G, et al. Safety and Effectiveness of BufferGel and 0.5% PRO2000 Gel for the Prevention of HIV Infection in Women. AIDS. 2011 Apr 24;25(7):957-66. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083640/. Last accessed on May 20, 2015.
- McCormack S, Ramjee G, Kamali A, et al. PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial. Lancet. 2010 Oct 16;376(9749):1329-37. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956883/. Last accessed on May 20, 2015.
- 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 May 20, 2015.
- 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(8):e157. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2494562/. Last accessed on May 20, 2015.
- Huskens D, Vermeire K, Profy AT, Schols D. The candidate sulfonated microbicide, PRO 2000, has potential multiple mechanisms of action against HIV-1. Antiviral Res. 2009 Oct;84(1):38-47. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19664662. Last accessed on May 20, 2015.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://nih.gov/health/clinicaltrials/index.htm. Last accessed on May 20, 2015.
- Guffey MB, Richardson B, Husnik M, et al. HPTN 035 Phase II/IIb Randomized Safety and Effectiveness Study of the Vaginal Microbicides BufferGel and 0.5% PRO 2000 for the Prevention of Sexually Transmitted Infections in Women. Sex Transm Infect. 2014 Aug;90(5):363-9. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278566/. Last accessed on May 20, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID): News Release, dated December 14, 2009. NIAID Web Bulletin: Major Study Finds Anti-HIV Gel Ineffective Among Women. Available at: http://www.niaid.nih.gov/news/newsreleases/Archive/2009/Pages/IneffectiveGel.aspx. Last accessed on May 20, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). Phase II/IIb Safety and Effectiveness Study of the Vaginal Microbicides BufferGel and 0.5% PRO 2000/5 Gel (P) for the Prevention of HIV Infection in Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 11, 2003. NLM Identifier: NCT00074425. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00074425. Last accessed on May 20, 2015.
- Endo Pharmaceuticals. An International Multi-centre, Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of 0.5% and 2% PRO 2000/5 Gels for the Prevention of Vaginally Acquired HIV Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 5, 2005. NLM Identifier: NCT00262106. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00262106. Last accessed on May 20, 2015.
Last Reviewed: May 20, 2015