Drugs

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: CONRAD, Gilead Sciences, Inc. Phase of Development: Tenofovir vaginal gel has been studied in a Phase III trial. Tenofovir rectal gel has been studied in a Phase II trial. Other tenofovir-based microbicides are in earlier phases of study.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and ClinicalTrials.gov3-8)

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).3

To learn how investigational drugs are tested during clinical trials, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

Tenofovir microbicide belongs to a class of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).9 NRTIs block an HIV enzyme, a type of protein, called reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and from spreading to other cells.

How do topical microbicides work?

How do topical microbicides work?

Topical microbicides come in many different forms, including gels, films, and vaginal rings (also called an intravaginal ring or IVR). These products are designed to prevent HIV infection during sex, so they are used close to where HIV might enter the body during sexual activities – either the vagina or rectum.9,10 Researchers have studied several different tenofovir-based microbicide products, including a vaginal gel, a rectal gel, a vaginal ring, a vaginal tablet, a vaginal film, and an enema.3-8

Topical microbicides may also be called topical pre-exposure prophylaxis (PrEP) products.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.

Which clinical trials are studying tenofovir microbicide?

Which clinical trials are studying tenofovir microbicide?

Tenofovir rectal gel

Study Names: MTN-017; NCT01687218
Phase: II
Status: This study has been completed.
Location: United States, Peru, Puerto Rico, South Africa, Thailand
Purpose: The purpose of this study was to look at the safety and acceptability of tenofovir rectal gel. Acceptability was measured by recording the side effects of tenofovir rectal gel and noting what participants liked and disliked about using the product, as well as whether study participants were likely to use the product in the future.4

Tenofovir vaginal gel

Study Names: (1) CAPRISA 004; NCT00441298, (2) CAPRISA 008; NCT01691768, and (3) CAPRISA 009; NCT01387022
Phase: CAPRISA 004 was a Phase IIb study. CAPRISA 008 and CAPRISA 009 were extension studies of CAPRISA 004.
Status: These studies have been completed.
Location: South Africa
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 acquired 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.11-14

Study Names: MTN-003; VOICE trial; NCT00705679
Phase: IIb
Status: This study has been completed.
Location: South Africa, Uganda, Zimbabwe
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).15

Study Names: FACTS 001; NCT01386294
Phase: III
Status: This study has been completed.
Location: South Africa
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 HSV-2 through sex.3

For more details on the studies listed above, see the Health Professional version of this drug summary.

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 formulation.16-18

What side effects might tenofovir microbicide cause?

What side effects might tenofovir microbicide cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of tenofovir microbicide listed above.

CAPRISA 004 (NCT00441298):

In this study, tenofovir vaginal gel was compared to a placebo, an inactive drug that is identical in appearance to the active drug being studied. Tenofovir did not cause more kidney, liver, genital, or pregnancy-related side effects than placebo. More cases of mild diarrhea were reported in the tenofovir vaginal gel group than in the placebo group.19

MTN-003; VOICE (NCT00705679):

There were no significant differences in safety between the tenofovir gel group and the placebo gel group in this study.20

MTN-017 (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).4,21,22

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 microbicide-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.

Some clinical trials may be looking for volunteer participants. 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.nlm.nih.gov/chemidplus/rn/147127-20-6. Last accessed on June 26, 2018.
  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 June 26, 2018.
  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 June 26, 2018.
  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 June 26, 2018.
  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 June 26, 2018.
  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 June 26, 2018.
  7. CONRAD. Phase I, 90-Day safety, pharmacokinetic, and pharmacodynamic study of intravaginal rings releasing tenofovir and levonorgestrel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 23, 2017. NLM Identifier: NCT03279120. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03279120. Last accessed on June 26, 2018.
  8. Johns Hopkins University. DREAM-01: optimization of a tenofovir enema for HIV prevention. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 11, 2016. NLM Identifier: NCT02750540. Available at: https://clinicaltrials.gov/ct2/show/NCT02750540. Last accessed on June 26, 2018.
  9. Shattock RJ, Rosenberg Z. Microbicides: Topical prevention against HIV. Cold Spring Harb Perspect Med. 2012 Feb;2(2):a007385. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281595/. Last accessed on June 26, 2018.
  10. 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 June 26, 2018.
  11. 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 June 26, 2018.
  12. 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 June 26, 2018.
  13. 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 June 26, 2018. [Archived at WebCite]
  14. 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 June 26, 2018.
  15. 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 June 26, 2018.
  16. 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 June 26, 2018.
  17. 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 June 26, 2018.
  18. 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 June 26, 2018.
  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: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001187/. Last accessed on June 26, 2018.
  20. 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: https://www.nejm.org/doi/pdf/10.1056/NEJMoa1402269. Last accessed on June 26, 2018. [Archived at WebCite]
  21. 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: 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 June 26, 2018. [Archived at WebCite]
  22. Microbicide Trials Network: News Release, dated February 24, 2016. International study finds rectal microbicide gel safe when used daily and with sex. Available at: https://mtnstopshiv.org/news/international-study-finds-rectal-microbicide-gel-safe-when-used-daily-and-sex . Last accessed on June 26, 2018.

Last Reviewed: June 26, 2018