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: 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. Intravaginal rings containing tenofovir are currently being studied in a Phase IIa trial. Other tenofovir-based microbicides are in earlier phases of study.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and ClinicalTrials.gov3-9)

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).10 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 more 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, films, and vaginal rings (also called intravaginal rings or IVRs). The products contain HIV medicine and are intended for vaginal or rectal use. The products are designed to safely block HIV transmission by delivering the HIV medicine to the mucocutaneous surfaces of the vagina or the rectum that may be exposed to HIV during sex.10,11

Which clinical trials are studying tenofovir-based microbicides?

Which clinical trials are studying tenofovir-based microbicides?

Tenofovir-based microbicides for rectal use 

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 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 I study that tested the safety and acceptability of a tenofovir vaginal gel when applied rectally
  • CHARM-01 (NCT01575405) and CHARM-02 (NCT01575418), Phase I 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.12-14

Tenofovir-based vaginal microbicides

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.15-18

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 three different strategies for preventing HIV. These strategies were (1) a vaginal microbicide (tenofovir vaginal gel), (2) the Food and Drug Administration (FDA)-approved oral HIV medicine tenofovir disoproxil fumarate (brand name: Viread), and (3) the FDA-approved oral HIV combination medicine emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada).19

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 could protect women from getting HIV and HSV-2 through sex.3

Intravaginal rings

Study Names: Protocol B17-144; NCT03762382
Phase: IIa
Status: This study has been enrolling by invitation.
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.9

A tenofovir IVR will also be studied in a Phase I trial (MTN-038; NCT03670355). The study is currently recruiting participants.20

Additional studies of tenofovir-based vaginal microbicides have been completed. These include a Phase I trial (NCT01694407) that evaluated tenofovir-containing vaginal tablets and a Phase I trial (FAME-04; NCT01989663) that assessed tenofovir vaginal gel and film formulations.5,6

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

CAPRISA 004 (NCT00441298):
In this study, tenofovir vaginal gel was compared to a placebo gel. The tenofovir gel did not cause more kidney, liver, genital, or pregnancy-related side effects than placebo gel. More cases of mild diarrhea were reported in the tenofovir vaginal gel group than in the placebo gel group.23

MTN-003; VOICE (NCT00705679):
There were no significant differences in safety concerns between the tenofovir gel and the other study products (the FDA-approved oral medicines tenofovir disoproxil fumarate and emtricitabine/tenofovir disoproxil fumarate and the gel and oral placebos) in this study.24

 FACTS 001 (NCT01386294):
In this Phase III 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.25

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 May 29, 2019
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed May 29, 2019
  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 May 29, 2019
  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 May 29, 2019
  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 May 29, 2019
  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 May 29, 2019
  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 May 29, 2019
  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. https://clinicaltrials.gov/ct2/show/NCT02750540. Accessed May 29, 2019
  9. 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/record/NCT03762382. Accessed May 29, 2019
  10. Shattock RJ, Rosenberg Z. Microbicides: topical prevention against HIV. Cold Spring Harb Perspect Med. 2012;2(2):a007385
  11. National Institute of Allergy and Infectious Diseases (NIAID). Microbicides to block transmission of HIV. https://www.niaid.nih.gov/diseases-conditions/microbicides. Accessed May 29, 2019
  12. 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 May 29, 2019
  13. 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 May 29, 2019
  14. 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 May 29, 2019
  15. 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 May 29, 2019
  16. 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. https://www.clinicaltrials.gov/ct2/show/NCT01691768. Accessed May 29, 2019
  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. http://programme.aids2016.org/Abstract/Abstract/3183. Accessed May 29, 2019
  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. https://www.clinicaltrials.gov/ct2/show/study/NCT01387022. Accessed May 29, 2019
  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 May 29, 2019
  20. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 1, randomized pharmacokinetic and safety study of a 90 Day intravaginal ring containing tenofovir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 12, 2018. NLM Identifier: NCT03670355. https://clinicaltrials.gov/ct2/show/record/NCT03670355. Accessed May 29, 2019
  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 May 29, 2019
  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 May 29, 2019
  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;329(5996):1168-1174. doi:10.1126/science.1193748
  24. Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372(6):509-518
  25. 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: May 29, 2019