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AIDSinfo Drug Database

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FDA-approved

Investigational

Tenofovir (microbicide)  Audio icon

Other Names: GS-1278, PMPA gel, TFV gel, tenofovir 1% gel, tenofovir gel
Drug Class: Microbicides
Molecular Formula: C9 H14 N5 O4 P
Registry Number: 147127-20-6 (CAS)
Chemical Name: [(1R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methylphosphonic acid
Chemical Class: Purine Nucleotides
Company: Gilead Sciences, Inc.
Phase of Development: Phase III (Tenofovir vaginal gel is in Phase III testing. Other tenofovir-based microbicide products are in Phase I and II studies.)
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Chemical Image:
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tenofovir
tenofovir
Molecular Weight: 287.2146
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and ClinicalTrials.gov3-7)

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.

To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.

What is tenofovir microbicide?

The topical microbicide form of tenofovir is an investigational drug that is being studied to prevent sexual transmission of HIV and herpes simplex virus type 2 (HSV-2). 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.8 (There are other forms of tenofovir-containing products, such as oral tenofovir disoproxil fumarate [brand name: Viread], that are different from the topical microbicide form. Oral tenofovir disoproxil fumarate is FDA approved for treating HIV infection and is taken by mouth.)

Tenofovir microbicide belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).9 NRTIs 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, NRTIs prevent HIV from multiplying and from spreading to other cells.

Several different forms of tenofovir-based microbicide products are being studied or have been studied, including a vaginal gel, a rectal gel, a vaginal ring (also known as an intravaginal ring or IVR), a vaginal tablet, and a vaginal film. The vaginal gel is furthest along in development.3-7,10,11 (Tenofovir gel for rectal use contains a reduced amount of glycerin, an inactive ingredient, and it may be referred to as reduced glycerin tenofovir gel.)4

How do topical microbicides work?

Topical microbicides can also be referred to as topical pre-exposure prophylaxis (PrEP) products.8,9 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 AIDSinfo Pre-Exposure Prophylaxis (PrEP) fact sheet.

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).9,12

Early development of microbicides focused on products that used non-antiretroviral (ARV) medicines. These products worked in various ways, such as by inactivating pathogens, strengthening the body’s natural defenses, or blocking virus from getting into healthy cells.13-15

Current microbicide research is mainly focused on testing products that contain ARV medicines. ARV-based microbicides work at a particular step in the HIV life cycle and act almost exclusively against HIV. They may contain more than one ARV medicine to help make the product more effective. ARV-based microbicides might:

  • prevent HIV entry into healthy cells;
  • prevent HIV from converting its RNA into DNA, which stops HIV from replicating;
  • prevent HIV from inserting its genetic material into the DNA of host cells, which stops HIV from replicating;
  • prevent HIV from becoming a mature virus that can infect healthy cells.13,16,17

Tenofovir microbicide works by preventing HIV from converting its RNA into DNA, which helps to stop HIV from replicating.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.18

  • 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.18
In most cases, an investigational drug must be proven effective and must show continued safety 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.18

In what phase of testing is tenofovir microbicide?

Tenofovir vaginal gel has been studied in Phase III clinical trials. Reduced glycerin tenofovir gel for rectal use is currently in Phase II development.2,4,10

(Other forms of tenofovir-based microbicides are in early development, including an intravaginal ring, vaginal tablet, and vaginal film.)5-7,11

What are some studies on tenofovir microbicide?

Tenofovir Vaginal Gel

Study Name: CAPRISA 004; NCT00441298
Phase: IIb
Location: South Africa
Participants: Women not infected with HIV
Purpose: The purpose of this study was to see how safely and how well tenofovir vaginal gel can protect women from getting HIV through sex.19-21

* An extension study known as CAPRISA 008 was also completed. The extension study provided participants with tenofovir gel and looked at the possibility of providing the gel through family planning services.10

For more details on these two studies, see the Health Professional version.



Study Name: MTN-003; VOICE trial; NCT00705679
Phase: IIb
Location: South Africa, Uganda, Zimbabwe
Participants: Women not infected with HIV
Purpose: The purpose of this study was to test three different strategies for preventing HIV. The three strategies were (1) a vaginal microbicide (tenofovir vaginal gel), (2) the FDA-approved oral HIV medicine called tenofovir disoproxil fumarate (brand name: Viread), and (3) the FDA-approved oral HIV combination medicine called emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada).22-24

For more details on this study, see the Health Professional version.



Study Name: FACTS 001; NCT01386294
Phase: III
Location: South Africa
Participants: Women not infected with HIV
Purpose: The purpose of this study was to see how safely and how well tenofovir vaginal gel can protect women from getting HIV and herpes simplex virus (HSV) through sex.3,25

For more details on this study, see the Health Professional version.



Tenofovir Rectal Gel

Study Name: MTN-017; NCT01687218
Phase: IIb
Location: United States, Peru, Puerto Rico, South Africa, Thailand
Participants: Men and transgender women not infected with HIV
Purpose: The purpose of this study was to look at the safety and acceptability of tenofovir rectal gel. Acceptability relates to (1) tenofovir rectal gel side effects experienced by participants, (2) participants’ likes and dislikes with using the product, and (3) whether or not study participants are likely to use the product in the future.4,26

For more details on this study, see the Health Professional version.

What side effects might tenofovir microbicide cause?

In the CAPRISA 004 study discussed under the previous question, tenofovir vaginal gel did not cause more side effects than placebo in terms of kidney, liver, genital, or pregnancy-related side effects. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) More cases of mild diarrhea were reported in the tenofovir vaginal gel group than in the placebo group.19

In the MTN-003 (VOICE) study, there were no significant differences in safety between the tenofovir gel group and the placebo gel group.27

In the MTN-017 study, the rectal gel was reported to be safe, with most side effects being minor. Rates of moderate side effects were the same in all three study groups, which included two rectal gel groups and a third group taking the oral HIV medicine emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada).28,29

Information on possible side effects of the tenofovir gel products is not complete. As testing of tenofovir gel continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying tenofovir microbicide?

More information about tenofovir gel-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 tenofovir microbicide. 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.18

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/147127-20-6. Last accessed on April 14, 2016.
  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 14, 2016.
  3. CONRAD. A Phase III, Multi-Centre, Randomized Controlled Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel in the Prevention of Human Immunodeficiency Virus Type 1 Infection in Women, and to Examine Effects of the Microbicide on the Incidence of Herpes Simplex Virus Type 2 Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 28, 2011. NLM Identifier: NCT01386294. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01386294. Last accessed on April 14, 2016.
  4. CONRAD. A Phase 2 Randomized Sequence Open Label Expanded Safety and Acceptability Study of Oral Emtricitabine/Tenofovir Disoproxil Fumarate Tablet and Rectally-Applied Tenofovir Reduced-Glycerin 1% Gel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 27, 2012. NLM Identifier: NCT01687218. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01687218. Last accessed on April 14, 2016.
  5. CONRAD. A Phase I Trial to Assess the Safety of Tenofovir Gel and Film Formulations: FAME 04. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 5, 2013. NLM Identifier: NCT01989663. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01989663. Last accessed on April 14, 2016.
  6. CONRAD. A Phase I Clinical Trial Assessing the Safety, Pharmacokinetics, Pharmacodynamics, and Disintegration Time of Vaginal Tablets Containing Tenofovir and/or Emtricitabine. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 17, 2012. NLM Identifier: NCT01694407. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01694407. Last accessed on April 14, 2016.
  7. Albert Einstein College of Medicine of Yeshiva University. Phase 1 Safety and Pharmacokinetic Study of Polyurethane Tenofovir Disoproxil Fumarate Vaginal Ring. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 19, 2013. NLM Identifier: NCT02006264. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02006264. Last accessed on April 14, 2016.
  8. National Institute of Allergy and Infectious Diseases (NIAID). NIAID Research on Microbicides. Available at: http://www.niaid.nih.gov/topics/hivaids/research/prevention/pages/topicalmicrobicides.aspx. Last accessed on April 14, 2016.
  9. 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 14, 2016.
  10. Centre for the AIDS Programme of Research in South Africa. Open-Label Randomized Controlled Trial to Assess the Implementation Effectiveness and Safety of 1% Tenofovir Gel Provision Through Family Planning Services in KwaZulu-Natal, South Africa. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 5, 2012. NLM Identifier: NCT01691768. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01691768. Last accessed on April 14, 2016.
  11. CONRAD. Phase I One-Month Safety, Pharmacokinetic, Pharmacodynamic, and Acceptability Study of Intravaginal Rings Releasing Tenofovir and Levonorgestrel or Tenofovir Alone. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November July 14, 2014. NLM Identifier: NCT02235662. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02235662. Last accessed on April 14, 2016.
  12. 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 14, 2016.
  13. Global Campaign for Microbicides website. About Microbicides—How do they work? Available at: http://www.global-campaign.org/the_science.htm#work. Last accessed on April 14, 2016.
  14. CONRAD website. Microbicide Development. Available at: http://www.conrad.org/microbicides.html. Last accessed on April 14, 2016.
  15. CONRAD website. Microbicide Mechanisms of Action. Available at: http://www.conrad.org/microbicides-research-mechanisms.html. Last accessed on April 14, 2016.
  16. Global Campaign for Microbicides. Antiretroviral (ARV)-Based Microbicides: The Promise and the Puzzle; 2010. Available at: http://www.global-campaign.org/clientfiles/FS-ARV-BasedMicrobicides[E].pdf. Last accessed on April 14, 2016.
  17. International Partnership for Microbicides (IPM) website. How ARV-based Microbicides Work. Available at: http://www.ipmglobal.org/why-microbicides/how-arv-based-microbicides-work. Last accessed on April 14, 2016.
  18. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on April 14, 2016.
  19. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women. Science. 2010 Sep 3;329(5996):1168-74. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001187/. Last accessed on April 14, 2016.
  20. Centre for the AIDS Programme of Research in South Africa. Phase IIb Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel for the Prevention of HIV Infection in Women in South Africa. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 27, 2007. NLM Identifier: NCT00441298. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00441298. Last accessed on April 14, 2016.
  21. Abdool Karim Q and Abdool Karim SS. CAPRISA 004: Effectiveness & safety of vaginal microbicide 1% tenofovir gel for prevention of HIV infection in women. 18th International AIDS Conference; July 18-23, 2010; Vienna, Austria. Sourced from: Contraceptive Research and Development (CONRAD): News & Press Releases, dated July 18, 2010. CAPRISA 004 Trial Results Presentation From AIDS 2010 Conference. Available at: http://www.conrad.org/media/news/92_CAPRISA%20004%20Results.pdf. Last accessed on April 14, 2016.
  22. Friend DR, Kiser PF. Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned. Antiviral Res. 2013 Sep;99(3):391-400. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23845918. Last accessed on April 14, 2016.
  23. National Institute of Allergy and Infectious Diseases (NIAID): News Release, dated March 4, 2013. Daily-Use HIV Prevention Approaches Prove Ineffective Among Women in NIH Study. Available at: http://www.niaid.nih.gov/news/newsreleases/2013/Pages/VOICEwomen.aspx. Last accessed on April 14, 2016.
  24. National Institute of Allergy and Infectious Diseases (NIAID). Phase 2B Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate Tablet and Emtricitabine/Tenofovir Disoproxil Fumarate Tablet for the Prevention of HIV Infection in Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 24, 2008. NLM Identifier: NCT00705679. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00705679. Last accessed on April 14, 2016.
  25. Contraceptive Research and Development (CONRAD): Press Release, dated February 24, 2015. FACTS 001 Results Presented at CROI 2015. Available at: http://www.conrad.org/news-pressreleases-107.html. Last accessed on April 14, 2016.
  26. Microbicide Trials Network (MTN): News Room. Backgrounder: MTN-017: Phase II Safety and Acceptability Study of Tenofovir Gel Reformulated for Rectal Use. Available at: http://www.mtnstopshiv.org/news/studies/mtn017/backgrounder. Last accessed on April 14, 2016.
  27. Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women. N Engl J Med. 2015 Feb 5;372(6):509-18. Available at: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1402269. Last accessed on April 14, 2016.
  28. Cranston R, Lama J, Richardson BA, et al. MTN-017: Rectal Phase 2 Extended Safety and Acceptability Study of 1% Tenofovir Gel. Abstract presented at: 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Abstract 108LB. Available at: http://www.croiconference.org/sessions/mtn-017-rectal-phase-2-extended-safety-and-acceptability-study-1-tenofovir-gel. Last accessed on April 14, 2016.
  29. Microbicide Trials Network: News Release, dated February 24, 2016. International Study Finds Rectal Microbicide Gel Safe When Used Daily and With Sex. Available at: http://www.mtnstopshiv.org/node/7237. Last accessed on April 14, 2016.


Last Reviewed: April 14, 2016

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