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Tenofovir (microbicide)

Tenofovir (microbicide)

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 Organization: Gilead Sciences, Inc. Phase of Development: Tenofovir vaginal gel is in Phase III development. Other tenofovir-based microbicide products are in earlier phases of study.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and ClinicalTrials.gov3-7)

What is an investigational drug?

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?

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.8,9 (There are other forms of tenofovir-containing products, such as oral tenofovir disoproxil fumarate [brand name: Viread]. 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 called an intravaginal ring or IVR), a vaginal tablet, and a vaginal film. The vaginal gel is furthest along in development.3-7

How do topical microbicides work?

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).9,10

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 1 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.11-13

Tenofovir is an ARV-based microbicide that 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?

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.14

  • 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.14
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.14 (Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population.) 

In what phase of testing is tenofovir microbicide?

In what phase of testing is tenofovir microbicide?

Tenofovir vaginal gel has been studied in a Phase III clinical trial. Tenofovir gel for rectal use has been studied in a Phase II clinical trial.2-4

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

What are some studies on tenofovir microbicide?

What are some studies on tenofovir microbicide?

Tenofovir vaginal gel

Study Names: (1) CAPRISA 004; NCT00441298, (2) CAPRISA 008; NCT01691768, and (3) CAPRISA 009; NCT01387022 
Sponsor: Centre for the AIDS Programme of Research in South Africa
Phase: CAPRISA 004 was a Phase IIb study. CAPRISA 008 and CAPRISA 009 were extension studies of CAPRISA 004.
Location: South Africa
Participants: Participants in CAPRISA 004 were sexually active women who were not infected with HIV. 
Purpose: The purpose of CAPRISA 004 was to look at the safety of tenofovir vaginal gel and to see how well the gel could protect women from getting HIV through sex. CAPRISA 008 provided the tenofovir vaginal gel to previous CAPRISA 004 participants who did not have HIV. The study looked at gel safety and the effectiveness of providing the gel through family planning services. In CAPRISA 009, participants were women who became infected with HIV during either CAPRISA 004 or CAPRISA 008. The CAPRISA 009 study looked at whether tenofovir vaginal gel affected any of the tenofovir-containing HIV medicines that the women were taking to control their HIV infection.15-18


Study Names: MTN-003; VOICE trial; NCT00705679
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Phase: IIb
Location: South Africa, Uganda, Zimbabwe
Participants: Participants included sexually active women who were not infected with HIV.
Purpose: The purpose of this study was to test 3 different strategies for preventing HIV. These strategies were (1) a vaginal microbicide (tenofovir vaginal gel), (2) the FDA-approved oral HIV medicine tenofovir disoproxil fumarate, and (3) the FDA-approved oral HIV combination medicine emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada).19


Study Names: FACTS 001; NCT01386294
Sponsor: CONRAD
Phase: III
Location: South Africa
Participants: Participants included sexually active women who were not infected with HIV.
Purpose: The purpose of this study was to look at the safety of tenofovir vaginal gel and to see how well the gel can protect women from getting HIV and herpes simplex virus (HSV) through sex.3


Tenofovir rectal gel

Study Names: MTN-017; NCT01687218
Sponsor: CONRAD
Phase: IIb
Location: United States, Peru, Puerto Rico, South Africa, Thailand
Participants: Participants were men and transgender women who were 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) what participants liked and disliked about using the product, and (3) whether or not study participants are likely to use the product in the future.4

For more details on the studies listed above, see the Health Professional version.

Additional studies on the vaginal and rectal gels have been completed, including:

  • MTN-007 (NCT01232803), a Phase I study that tested the safety and acceptability of a tenofovir vaginal gel when used rectally
  • CHARM-01 (NCT01575405) and CHARM-02 (NCT01575418), Phase I studies that evaluated the safety, acceptability, and drug properties of 3 gel formulations used rectally: 2 vaginal formulations and a rectal formulation20-22
 

What side effects might tenofovir microbicide cause?

What side effects might tenofovir microbicide cause?

In the CAPRISA 004 study (NCT00441298) 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.23

In the MTN-003 (VOICE) study (NCT00705679), there were no significant differences in safety between the tenofovir gel group and the placebo gel group.24

In the MTN-017 study (NCT01687218), the rectal gel was reported to be safe, with most side effects being minor. Rates of moderate side effects were the same in all 3 study groups, which included 2 rectal gel groups and a third group taking the oral HIV medicine emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada).4,25,26

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?

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.

How can I find more information about participating in a clinical trial?

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.14

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

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.sis.nlm.nih.gov/chemidplus/rn/147127-20-6. Last accessed on May 23, 2017.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on May 23, 2017.
  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 May 23, 2017.
  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 May 23, 2017.
  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 May 23, 2017.
  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 May 23, 2017.
  7. Albert Einstein College of Medicine, Inc. Phase 1 safety and pharmacokinetic study of a polyurethane tenofovir disoproxil fumarate vaginal ring in sexually active women (TDF IVR-002). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 22, 2016. NLM Identifier: NCT02762617. Available: https://www.clinicaltrials.gov/ct2/show/NCT02762617. Last accessed on May 23, 2017.
  8. National Institute of Allergy and Infectious Diseases (NIAID). Microbicides to block transmission of HIV. Available at:https://www.niaid.nih.gov/diseases-conditions/microbicides. Last accessed on May 23, 2017.
  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 May 23, 2017.
  10. 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 23, 2017.
  11. 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 May 23, 2017.
  12. 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 May 23, 2017.
  13. 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 May 23, 2017.
  14. 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 May 23, 2017.
  15. 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 May 23, 2017.
  16. 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 May 23, 2017.
  17. Mansoor LE, Abdool Karim Q, Mngadi KT, et al. Good adherence in trial of topical pre-exposure prophylaxis integrated into family planning services. Abstract presented at: International AIDS Conference; July 18-22, 2016; Durban, South Africa. Abstract FRAE0102. Available at: http://programme.aids2016.org/Abstract/Abstract/3183. Last accessed on May 23, 2017.
  18. Centre for the AIDS Programme of Research in South Africa. Open label randomized controlled trial to assess the impact of prophylactic exposure to tenofovir gel on the efficacy of subsequent tenofovir-containing antiretroviral therapy on viral suppression. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 21, 2011. NLM Identifier: NCT01387022. Available at: https://www.clinicaltrials.gov/ct2/show/study/NCT01387022. Last accessed on May 23, 2017.
  19. 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 May 23, 2017.
  20. CONRAD. A Phase 1 randomized, double-blinded, placebo-controlled rectal safety and acceptability study of tenofovir 1% gel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 1, 2010. NLM Identifier: NCT01232803. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01232803. Last accessed on May 23, 2017.
  21. Ian McGowan. A randomized, double blind Phase 1 safety, acceptability, and pharmacokinetic study comparing three formulations of tenofovir 1% gel administered rectally to HIV-1 seronegative adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 29, 2012. NLM Identifier: NCT01575405. Available at: https://clinicaltrials.gov/ct2/show/NCT01575405. Last accessed on May 23, 2017.
  22. Ian McGowan. An exploratory, double-blinded, randomized, pharmacokinetic and safety study of three rectally-applied tenofovir 1% microbicide gel formulations. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2012. NLM Identifier: NCT01575418. Available at: https://clinicaltrials.gov/ct2/show/NCT01575418. Last accessed on May 23, 2017.
  23. 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 May 23, 2017.
  24. 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 May 23, 2017.
  25. 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 May 23, 2017.
  26. 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 May 23, 2017.
 

Last Reviewed: May 23, 2017