NOTE: The development of carrageenan (brand name: Carraguard) as a single-drug microbicide for preventing sexually acquired HIV infection has been discontinued.
The study of carrageenan as a single-drug microbicide for preventing HIV infection was discontinued. Data from a Phase III study showed that carrageenan vaginal gel was ineffective in protecting women against sexually acquired HIV infection.3,4
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 carrageenan?
Carrageenan (brand name: Carraguard) is an investigational drug that has been studied to prevent sexual transmission of HIV and other sexually transmitted infections (STIs).4-6 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.7
Carrageenan belongs to a group of drugs called polyanion-based entry inhibitors.8 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
Carrageenan formulated as a single-drug microbicide has been developed in a gel form. The gel has been studied for vaginal use.4 Carrageenan is also being studied as part of a combination microbicide gel. The combination gel contains carrageenan, zinc acetate, and an investigational non-nucleoside reverse transcriptase inhibitor known as MIV-150.11
How do topical microbicides work?
Topical microbicides can also be referred to as topical pre-exposure prophylaxis (PrEP) products.7,12 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).12,13 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 micoorganisms);
- 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.7
Carrageenan works by blocking HIV from attaching to susceptible, healthy cells.8,14
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.15
- 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.15
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.15
In what phase of testing is carrageenan?
As a single-drug microbicide, carrageenan vaginal gel has been studied in a Phase III clinical trial.2
The development of carrageenan vaginal gel as a single-drug microbicide for preventing HIV infection has since been discontinued.3
What are some studies on carrageenan?
Study Name: NCT00213083
Location: South Africa
Participants: HIV-uninfected women
Purpose: To look at the safety and effectiveness of carrageenan vaginal gel for preventing sexually acquired HIV infection in women
Study Design: Over 6000 participants were randomly assigned to use either carrageenan vaginal gel or a placebo gel. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) Women were instructed to apply the gels vaginally and within 1 hour before vaginal intercourse. Participants used the gels for up to 2 years.
- Carrageenan vaginal gel was not effective in preventing sexually transmitted HIV infection in women.
- Adherence to using the gel during each sex act was about 42%. (Adherence means using a medicine exactly as prescribed.)
- At the end of the study, researchers tested a subset of participants for certain types of human papillomavirus (HPV) infection. They found that among the women who used the gel as prescribed, there were fewer women infected with HPV in the carrageenan group than in the placebo group. This suggests that carrageenan gel may possibly protect women against certain types of HPV. But more studies are needed to prove this because it is not known when the women were infected with HPV.
- In terms of safety, carrageenan vaginal gel was determined to be safe.4,16-19
What side effects might carrageenan cause?
In the Phase III study discussed under the previous question, no concerning side effects associated with carrageenan microbicide gel were reported.4,17
If testing of carrageenan microbicide gel continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying carrageenan?
More information about carrageenan-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 carrageenan. 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.15
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/9000-07-1. Last accessed on May 6, 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 6, 2015.
- Singh O, Garg T, Rath G, Goyal AK. Microbicides for the Treatment of Sexually Transmitted HIV Infections. J Pharm. 2014 Feb 12;2014 doi:10.1155/2014/352425. Available at: http://www.hindawi.com/journals/jphar/2014/352425/. Last accessed on May 6, 2015.
- Skoler-Karpoff S, Ramjee G, Ahmed K, et al. Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Dec 6;372(9654):1977-87. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19059048. Last accessed on May 6, 2015.
- Marais D, Gawarecki D, Allan B, et al. The effectiveness of Carraguard, a vaginal microbicide, in protecting women against high-risk human papillomavirus infection. Antivir Ther. 2011;16(8):1219-26. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22155903. Last accessed on May 6, 2015.
- Trapp S, Turville SG, Robbiani M. Slamming the door on unwanted guests: why preemptive strikes at the mucosa may be the best strategy against HIV. J Leukoc Biol. 2006 Nov;80(5):1076-83. Available at: http://www.jleukbio.org/content/80/5/1076.long. Last accessed on May 6, 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 6, 2015.
- Pirrone V, Wigdahl B, Krebs FC. The rise and fall of polyanionic inhibitors of the human immunodeficiency virus type 1. Antiviral Res. 2011 Jun;90(3):168-82. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21439325. Last accessed on May 6, 2015.
- International Partnership for Microbicides (IPM) website. Glossary: Polyanion. Available at: http://www.ipmglobal.org/our-work/glossary/polyanion. Last accessed on May 6, 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 6, 2015.
- Population Council. A Phase 1, Double-Blind, Parallel, Placebo-Controlled, Randomized Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Acceptability of PC-1005 Microbicide Gel Formulation in HIV-seronegative Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 8, 2014. NLM Identifier: NCT02033109. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02033109. Last accessed on May 6, 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 6, 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;5(8):e157; discussion e157. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2494562/. Last accessed on May 6, 2015.
- The Rockefeller Foundation. The Science of Microbicides: Accelerating Development. A Report by the Science Working Group of the Microbicide Initiative. Page 25. Available from The Global Campaign for Microbicides (GCM) at: http://www.global-campaign.org/clientfiles/rep4_science.pdf. Last accessed on May 6, 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 6, 2015.
- The Population Council, Inc. Phase III Study of the Efficacy and Safety of the Microbicide Carraguard in Preventing HIV Seroconversion in Women (Population Council Protocol 322): Summary. Available at: http://www.popcouncil.org/uploads/pdfs/MIC_Phase%203%20Protocol%20Summary_Final_2_6_08.pdf. Last accessed on May 6, 2015.
- The Population Council, Inc.: Press Release, dated February 18, 2008. Trial Shows Anti-HIV Microbicide Is Safe, but Does Not Prove It Effective. Available at: http://www.popcouncil.org/news/trial-shows-anti-hiv-microbicide-is-safe-but-does-not-prove-it-effective. Last accessed on May 6, 2015.
- Marais D, Gawarecki D, Allan B, et al. The effectiveness of Carraguard, a vaginal microbicide, in protecting women against high-risk human papillomavirus infection. Antivir Ther. 2011;16(8):1219-26. Available at: http://www.intmedpress.com/serveFile.cfm?sUID=f9170522-1145-4fd4-94fe-99099cc9d23d. Last accessed on May 6, 2015.
- Population Council. Phase 3 Study of the Efficacy and Safety of the Microbicide Carraguard® in Preventing HIV Seroconversion in Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 13, 2005. NLM Identifier: NCT00213083. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00213083. Last accessed on May 6, 2015.
Last Reviewed: May 6, 2015