Drugs

Tenofovir-Based Microbicides

Tenofovir-Based Microbicides

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: Centre for the AIDS Programme of Research in South Africa, Gilead Sciences, Inc. Phase of Development: Tenofovir vaginal gel has been studied in a Phase 3 trial. Tenofovir rectal gel has been studied in a Phase 2 trial. Intravaginal rings containing tenofovir are currently being studied in a Phase 2a trial. Other tenofovir-based microbicides are in earlier phases of study.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and ClinicalTrials.gov3-12)

What is a tenofovir-based microbicide?

What is a tenofovir-based microbicide?

Tenofovir-based topical microbicides are investigational products that are being studied to prevent sexual transmission of HIV. They have also been studied to prevent herpes simplex virus type 2 (HSV-2).3

Tenofovir, the HIV drug used in tenofovir-based microbicides, belongs to a class of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).13 NRTIs block an HIV enzyme called reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and from spreading to other cells.

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

How do topical microbicides work?

How do topical microbicides work?

Topical microbicides come in many different forms, including gels, creams, films, and vaginal rings (also called intravaginal rings or IVRs). 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.13,14 Researchers have studied several different tenofovir-based microbicide products, such as vaginal and rectal gels and inserts, intravaginal rings, and a rectal douche.3,4,7,9–12

Which clinical trials are studying tenofovir-based microbicides?

Which clinical trials are studying tenofovir-based microbicides?

Tenofovir-based microbicides for rectal use 

Rectal gel
Study Names
: MTN-017; NCT01687218
Phase: 2
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 they were likely to use the product in the future.4

Additional studies of tenofovir-based microbicides for rectal use have been completed, including:

  • MTN-007 (NCT01232803): A Phase 1 study that tested the safety and acceptability of a tenofovir vaginal gel when applied rectally.15
  • CHARM-01 (NCT01575405) and CHARM-02 (NCT01575418): Phase 1 studies that evaluated the safety, acceptability, and drug properties of three different formulations of rectally-applied tenofovir gel: two vaginal formulations and a rectal formulation.16,17

Other rectal dosage forms
A tenofovir rectal douche is being studied in two Phase 1 trials: DREAM-02 (NCT04195776) and DREAM-03 (NCT04016233). See the ClinicalTrials.gov record for the DREAM-02 study's status. The DREAM-03 study is currently recruiting participants.9,10

A tenofovir alafenamide/elvitegravir insert for rectal administration is also in Phase 1 study (MTN-039; NCT04047420). This study is currently recruiting participants.12

Tenofovir-based vaginal microbicides

Vaginal gel
Study Names: FACTS 001; NCT01386294
Phase: 3
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 could protect women from getting HIV and HSV-2 through sex.3

Additional clinical trials evaluating tenofovir vaginal gel have also been completed. These include the Phase 2b CAPRISA 004 trial (NCT00441298) and the Phase 2b VOICE trial (MTN-003; NCT00705679).18,19

Intravaginal rings
Study Names: Protocol B17-144; NCT03762382
Phase: 2a 
Status: This study is ongoing, but not recruiting participants.
Location: Kenya
Purpose: The purpose of this study is to evaluate the safety, pharmacokinetics, tolerability and acceptance of two tenofovir-based IVRs (one delivering both tenofovir and levonorgestrel, the other delivering tenofovir only) in women from Kenya. Both tenofovir-based IVRs will be compared to a placebo IVR.8

A Phase 1 trial (NCT03255915) is evaluating the safety and pharmacokinetics of an IVR delivering both tenofovir disoproxil fumarate and emtricitabine. This study is currently recruiting participants.20

Other vaginal dosage forms
Additional studies of tenofovir-based vaginal microbicides have been completed. These include a Phase 1 trial (NCT01694407) that evaluated tenofovir-containing vaginal tablets and a Phase 1 trial (FAME-04; NCT01989663) that assessed tenofovir vaginal gel and film formulations.5,6 A vaginal insert containing tenofovir alafenamide and elvitegravir has also been evaluated in a Phase 1 study (NCT03762772).11

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

What side effects might tenofovir-based microbicides cause?

What side effects might tenofovir-based microbicides 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-based microbicides listed above.

MTN-017 (NCT01687218):
The tenofovir rectal gel was reported to be safe, with most side effects being minor. Rates of moderate side effects were the same for all three study regimens: tenofovir rectal gel used daily, tenofovir rectal gel used before and after anal sex, and the oral HIV combination medicine emtricitabine/tenofovir disoproxil fumarate used daily.4,21,22 

 FACTS 001 (NCT01386294):
In this Phase 3 study, tenofovir vaginal gel was compared to a placebo vaginal gel. The number of participants who had moderately severe side effects was greater in the tenofovir group than in the placebo group. The most common product-related side effects of moderate or greater severity were very low levels of phosphate (hypophosphatemia), genital symptoms, and elevated liver enzyme levels. No product-related serious side effects occurred during the study.23

Because tenofovir-based microbicides are still being studied, information on possible side effects of the products is not complete. As testing of tenofovir-based microbicides continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying tenofovir-based microbicides?

Where can I get more information about clinical trials studying tenofovir-based microbicides?

More information related to research studies of tenofovir-based microbicides 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: Tenofovir. https://chem.nlm.nih.gov/chemidplus/rn/147127-20-6. Accessed March 4, 2020
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed March 4, 2020
  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. https://www.clinicaltrials.gov/ct2/show/NCT01386294. Accessed March 4, 2020
  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. https://www.clinicaltrials.gov/ct2/show/NCT01687218. Accessed March 4, 2020
  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. https://www.clinicaltrials.gov/ct2/show/NCT01989663. Accessed March 4, 2020
  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. https://www.clinicaltrials.gov/ct2/show/NCT01694407. Accessed March 4, 2020
  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. https://www.clinicaltrials.gov/ct2/show/NCT03279120. Accessed March 4, 2020
  8. CONRAD. Phase IIa, 90-day safety, adherence, and acceptability study of intravaginal rings releasing tenofovir with and without levonorgestrel among women in Western Kenya. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 16, 2018. NLM Identifier: NCT03762382. https://clinicaltrials.gov/ct2/show/study/NCT03762382. Accessed March 4, 2020
  9. Johns Hopkins University. A Phase 1 open label study evaluating the distribution of a tenofovir douche in combination with tap water douching and simulated receptive anal intercourse (DREAM-02). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 10, 2019. NLM Identifier: NCT04195776. https://clinicaltrials.gov/ct2/show/NCT04195776. Accessed March 4, 2020
  10. Johns Hopkins University. A Phase I, open-label multiple dose safety, pharmacokinetic, pharmacodynamic, and acceptability study of tenofovir rectal douche. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 9, 2019. NLM Identifier: NCT04016233. https://clinicaltrials.gov/ct2/show/NCT04016233. Accessed March 4, 2020
  11. CONRAD. A Phase I study to assess safety, pharmacokinetics, and pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 16, 2018. NLM Identifier: NCT03762772. https://clinicaltrials.gov/ct2/show/NCT03762772. Accessed March 4, 2020
  12. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 1 open label safety and pharmacokinetic study of rectal administration of a tenofovir alafenamide/elvitegravir insert at two dose levels. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 5, 2019. NLM Identifier: NCT04047420. https://clinicaltrials.gov/ct2/show/NCT04047420. Accessed March 4, 2020
  13. Shattock RJ, Rosenberg Z. Microbicides: topical prevention against HIV. Cold Spring Harb Perspect Med. 2012;2(2):a007385.
  14. National Institute of Allergy and Infectious Diseases (NIAID). Microbicides to block transmission of HIV. https://www.niaid.nih.gov/diseases-conditions/microbicides. Accessed March 4, 2020
  15. 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. https://www.clinicaltrials.gov/ct2/show/NCT01232803. Accessed March 4, 2020
  16. 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. https://clinicaltrials.gov/ct2/show/NCT01575405. Accessed March 4, 2020
  17. 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. https://clinicaltrials.gov/ct2/show/NCT01575418. Accessed March 4, 2020
  18. 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. https://www.clinicaltrials.gov/ct2/show/NCT00441298. Accessed March 4, 2020
  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. https://www.clinicaltrials.gov/ct2/show/NCT00705679. Accessed March 4, 2020
  20. Oak Crest Institute of Science. Randomized order, controlled, double blind, crossover early Phase 1 pilot study to assess safety and pharmacokinetics of a tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) releasing IVR over 28 days compared to placebo. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 26, 2017. NLM Identifier: NCT03255915. https://clinicaltrials.gov/ct2/show/NCT03255915. Accessed March 4, 2020
  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. http://www.croiconference.org/sessions/mtn-017-rectal-phase-2-extended-safety-and-acceptability-study-1-tenofovir-gel. Accessed March 4, 2020
  22. Microbicide Trials Network. News Release, dated February 24, 2016. International study finds rectal microbicide gel safe when used daily and with sex. https://mtnstopshiv.org/news/international-study-finds-rectal-microbicide-gel-safe-when-used-daily-and-sex. Accessed March 4, 2020
  23. Delany-Moretlwe S, Lombard C, Baron D, et al. Tenofovir 1% vaginal gel for prevention of HIV-1 infection in women in South Africa (FACTS-001): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2018;18(11):1241-1250. doi:10.1016/S1473-3099(18)30428-6

Last Reviewed: March 4, 2020

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