Tenofovir gel, also known as PMPA gel, is a type of medicine called a microbicide. Microbicides are substances that protect the body from infection by microorganisms such as bacteria, viruses, and fungi. Microbicides work by either destroying the microbes or preventing them from establishing an infection.
HIV/AIDS-Related Uses
Tenofovir gel is an investigational medicine that is not yet approved by the FDA for use outside of clinical trials. It is being studied for the prevention of HIV transmission. This medicine does not cure HIV infection or AIDS and is being studied to reduce the risk of passing the virus to other people.
Dosage Form/Administration
Tenofovir gel comes in topical gel form and is applied vaginally.
Recommended Daily Dose
Different strengths and doses of tenofovir gel are being studied. Tenofovir 0.3% and 1% gels are being studied for once-daily, twice-daily, or as needed use.
Contraindications
Individuals should tell a doctor about any medical problems before taking this medicine.
Possible Side Effects
Along with its desired effects, tenofovir gel may cause some unwanted effects. Most effects have been mild and limited to the application area. Although not all of these effects are known, vaginal itching, redness, and discharge have been reported.
Drug and Food Interactions
A doctor should be notified of any other medications being taken, including prescription, nonprescription (over-the-counter), or herbal medications.
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use Tenofovir.
Last Updated: June 1, 2009
Drug Description
Tenofovir is an adenosine nucleoside monophosphate reverse transcriptase inhibitor and viral replication inhibitor. [1]
References
[1] Curr Pharm Des 2004;10(3):315-36
HIV/AIDS-Related Uses
Tenofovir gel, also known as PMPA gel, is being investigated in Phase II monotherapy [1] studies as a vaginal microbicide for the prevention of HIV transmission. Tenofovir is also being studied in combination with PRO 2000, another investigational vaginal microbicide. [2] [3] Approved oral formulations of its prodrug, tenofovir disoproxil fumarate (tenofovir DF), are used to treat HIV. [4]
References
[1] ClinicalTrials.gov 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. Available at: http://clinicaltrials.gov/ct2/show/NCT00441298?term=phase+IIb%2C+pmpa&rank=1. Accessed 06/01/09.
[2] Treatment Action Group 2008 Pipeline Report - Table 2: PrEP and Microbicides Pipeline 2008. Available at:. http://www.treatmentactiongroup.org/search.aspx?terms=tenofovir. Accessed 06/01/09.
[3] AIDS 2006 Feb 26;20(4): 543-51
[4] Gilead Sciences Investors: News Releases. Gilead Announces Initiation of NIH-sponsored Phase I Trial to Evaluate Tenofovir Topical Gel as Preventive for Vaginal Transmission of HIV [press release], May 21, 2002. Available at: http://www.gilead.com/wt/sec/pr_298978. Accessed 06/01/09.
Dosing Information
Mode of Delivery
Intravaginal. [1]
Dosage Form
Tenofovir gel is available in 0.3% and 1% concentrations. In clinical studies, it is applied vaginally once or twice daily. Precoital applications are also being investigated. [2]
Tenofovir gel is packaged in 6-gram tubes and in 4-gram, single-dose applicators. [3]
References
[1] AIDS 2006 Feb 26;20(4): 543-51
[2] AIDS 2006 Feb 26;20(4): 543-51
[3] AIDS 2006 Feb 26;20(4): 543-51
Pharmacology
Tenofovir, a nucleotide analogue, is characterized by its ability to enter and inhibit viral replication in HIV-infected and HIV-uninfected or resting cells, thus forming active drug reservoirs. [1]
Tenofovir has a long intracellular half-life. [2] Serum plasma concentrations with tenofovir gel application have ranged from 3 to 25.8 ng/mL, remaining lower than the 50 ng/mL minimum plasma concentration achieved with oral tenofovir DF. [3]
Animal studies support the use of tenofovir gel as a microbicide. A small study of four rhesus macaques administered intravaginal tenofovir gel, beginning 24 hours before and continuing 48 hours after intravaginal inoculation with simian immunodeficiency virus, resulted in 100% protection, compared with evidence of infection in both of two macaques receiving placebo gel. [4]
HPTN 050, an open-label, Phase I trial, evaluated tenofovir 0.3% and 1% gels, administered daily or twice daily for 2 weeks in sexually abstinent HIV-infected and HIV-uninfected women to determine toxicity, pharmacokinetics, and gel acceptability. Fourteen of 25 women (56%) experienced low but detectable serum tenofovir levels. Asymptomatic bacterial vaginosis in 29 women resolved in 14 (48%) after gel administration. No new resistance mutations evolved, and no patients had high-level tenofovir mutations, such as K65R. [5] [6] Results from the HPTN 050 study have shown tenofovir gel to be generally safe and acceptable. [7]
HPTN 059 a multicenter, randomized, controlled Phase II trial involving HIV-uninfected women, determined the safety and acceptability of tenofovir 1% gel administered over 24 weeks, with a 48-week follow-up. Patients were assigned to one of four cohorts: tenofovir 1% daily; placebo daily; tenofovir 1%, coitally dependent; or placebo, coitally dependent. Primary outcome measures included macroscopic evidence of damage to the cervical, vulvar, or vaginal epithelium, severe erythema, or severe edema, related or not related to the study gel or applicator. [8] Results of the study have yet to be published.
MTN- 001 and MTN-002 are two tenofovir gel pharmacokinetic studies currently in the recruitment stage. MTN-001 is a randomized, open-label, crossover, Phase II trial evaluating the adherence and acceptability of tenofovir gel in a study population. MTN-001 will employ three regimens for comparative purposes, including the use of oral tenofovir dispoproxil fumarate. Primary outcome measures will include self-reported adherence to each regimen, proportion of participants who indicate they would be unlikely to use study product in the future, area under the concentration-time curve (AUC), maximum serum concentrations (Cmax), and minimum serum concentrations (Cmin). [9] MTN-002 is a non-randomized, open-label, cross-over Phase I trial which will assess term pregnancy single-dose pharmacokinetics (PK) of tenofovir 1% gel in HIV uninfected pregnant women. Primary outcome measures will include maternal third trimester pharmacokinetic measures (AUC and Cmax), endometrial tenofovir levels, and placental transfer (cord blood tenofovir levels, placental tissue tenofovir levels, and amniotic fluid tenofovir levels). [10]
MTN-003 is a Phase IIb, safety and effectiveness study exploring tenofovir 1% gel. It is designed to determine the safety and effectiveness of daily tenofovir 1% gel as compared to a vaginal placebo gel, and the safety and effectiveness of oral tenofovir disoproxil fumarate, and oral FTC/TDF compared to an oral placebo preventing HIV infection among women at risk for sexually transmitted infections. MTN-003 is not yet open to participants. [11]
TFV 010 is a randomized, double-blind, placebo-controlled Phase I study of tenofovir gel, which is currently in development and not yet open for participant recruitment. The purpose of the study is to assess whether there is a measurable response to daily vaginal applications of 1% tenofovir gel in women at low risk for HIV infection. TFV 010 will measure the mucosal response to daily intravaginal applications of 1% tenofovir gel versus placebo in two groups of women. Primary outcomes measures are changes in cytokines, chemokines, and other mediators of innate immunity. [12]
References
[1] Gilead Sciences Investors: News Releases. Gilead Announces Initiation of NIH-sponsored Phase I Trial to Evaluate Tenofovir Topical Gel as Preventive for Vaginal Transmission of HIV [press release], May 21, 2002. Available at: http://www.gilead.com/wt/sec/pr_298978. Accessed 06/01/09.
[2] Gilead Sciences News Releases. Gilead Announces Initiation of NIH-sponsored Phase I Trial to Evaluate Tenofovir Topical Gel as Preventive for Vaginal Transmission of HIV [press release], May 21, 2002. Available at: http://www.gilead.com/wt/sec/pr_298978. Accessed 06/01/09.
[3] AIDS 2006 Feb 26;20(4):543-51
[4] Conf Retroviruses Opportunistic Infect 13th, 2006. Abstract 569.
[5] Gilead Sciences Investors: News Releases. Gilead Announces Initiation of NIH-sponsored Phase I Trial to Evaluate Tenofovir Topical Gel as Preventive for Vaginal Transmission of HIV [press release], May 21, 2002. Available at: http://www.gilead.com/wt/sec/pr_298978. Accessed 06/01/09.
[6] AIDS 2006 Feb 26;20(4):543-51
[7] HPTN Phase II Expanded Safety and Acceptability Study of the Vaginal Microbicide 1% Tenofovir Gel. Available at: http://www.hptn.org/research_studies/hptn059.asp. Accessed 06/01/09.
[8] HPTN - Phase II Expanded Safety and Acceptability Study of the Vaginal Microbicide 1% Tenofovir Gel. Available at: http://www.hptn.org/research_studies/hptn059.asp. Accessed 06/01/09.
[9] ClinicalTrials.gov Phase 2 Adherence and Pharmacokinetics Study of Oral and Vaginal Preparations of Tenofovir. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00592124?term=mtn-001&rank=1. Accessed 06/01/09.
[10] ClinicalTrials.gov Phase I Study of the Maternal Single-Dose Pharmacokinetics and Placental Transfer of Tenofovir 1% Vaginal Gel Among Healthy Term Gravidas Available at: http://www.clinicaltrials.gov/ct2/show/NCT00540605?term=mtn-002&rank=1. Accessed 06/01/09.
[11] ClinicalTrials.gov 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. Available at: http://clinicaltrials.gov/ct2/show/NCT00705679?term=mtn+003&rank=2. Accessed 06/01/09.
[12] ClinicalTrials.gov Effect of Repeated Applications of Tenofovir Gel on Mucosal Mediators of Immunity and Intrinsic Antimicrobial Activity of Cervicovaginal Secretions in Women at Low Risk for HIV-1 Infection. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00594373?term=tenofovir+gel&rank=1. Accessed 06/01/09.
Adverse Events/Toxicity
In an open-label, Phase I trial evaluating tenofovir 0.3% and 1% gel concentrations in HIV-uninfected and HIV-infected women, the gel was well tolerated. Although 92% of patients experienced at least one adverse effect, 87% were mild and 70% were genitourinary. Thirty-two percent of patients experienced gastrointestinal effects. One severe adverse effect involving lower abdominal cramping in a participant using 0.3% tenofovir gel twice daily was considered possibly drug-related. [1]
The most common adverse effects noted were itching (23%), redness (18%), discharge (15%), irregular menstruation (13%), and uterine bleeding (11%). Vaginal candidiasis occurred in 5% of women while using the gel. [2]
In irritation studies, tenofovir 0.3% and 1% gels, adjusted to pH 4 to 5, appear nearly equal to carrier vehicles in irritation scores. [3]
References
[1] AIDS 2006 Feb 26;20(4): 543-51
[2] AIDS 2006 Feb 26;20(4): 543-51
[3] AIDS 2006 Feb 26;20(4): 543-51
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use Tenofovir.
Chemistry
CAS Name
Phosphonic acid, (((1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)- [1]
CAS Number
147127-20-6 [2]
Molecular Formula
C9-H14-N5-O4-P
Elemental Composition
C37.64%, H4.91%, N24.38%, O22.28%, P10.78%
Molecular Weight
287.21
Melting Point
279 C
Physical Description
Clear, transparent, viscous gel. [3]
References
[1] ChemIDplus Available at:http://chem.sis.nlm.nih.gov/chemidplus/jsp/common/ChemInfo.jsp?calledFrom=lite&type=names. Accessed 06/01/09.
[2] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemlite.jsp. Accessed 06/04/08.
[3] AIDS 2006 Feb 26;20(4): 543-51
Further Reading
Tenofovir gel studied. AIDS Patient Care STDS. 2002 Aug;16(8):401-2.
D'Cruz OJ, Uckun FM. Clinical development of microbicides for the prevention of HIV infection. Curr Pharm Des. 2004;10(3):315-36.
Meyer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Masse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L; HPTN 050 Protocol Team. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS 2006 Feb 28;20(4):543-551.
HPTN059: Phase II Expanded Safety and Acceptability Study of the Vaginal Microbicide 1% Tenofovir Gel. Available at: http://www.hptn.org/research_studies/hptn059.asp. Accessed 06/01/09.
Safety and Acceptability of a Vaginal Microbicide. Available at: http://www.clinicaltrials.gov/show/NCT00111943. Accessed 06/01/09.
Last Updated: June 1, 2009