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 maraviroc?
Maraviroc (brand name: Selzentry) is a drug that has been approved by FDA for treating HIV infection.3 It is currently being studied to see if it can also be used to prevent HIV infection.4,5
Maraviroc belongs to a class (group) of HIV drugs called entry and fusion inhibitors.1 Entry and fusion inhibitors block HIV from getting into and infecting certain cells of the immune system. This prevents HIV from multiplying.
Maraviroc works by attaching to a protein on the surface of the immune cells. The protein is called the CCR5 co-receptor. When maraviroc attaches to the CCR5 co-receptor, certain strains of HIV—called R-5 tropic virus—cannot attach to, enter, or infect the cell.2
Some studies have shown that the oral form of maraviroc is quickly absorbed by the body and accumulates in high concentrations in the tissues of the vagina, cervix, and rectum. Because of this, oral maraviroc is being studied as a possible medicine for HIV pre-exposure prophylaxis (PrEP). (PrEP is meant to help prevent HIV infection in people who don’t have HIV but who are at high risk of becoming infected with HIV. For more information on PrEP, see the AIDSinfo Pre-Exposure Prophylaxis [PrEP] fact sheet.)4,6-8
Other forms of maraviroc, including an intravaginal ring (IVR) and a gel, are also being studied for preventing HIV infection and are in Phase I studies.4,5
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.9
- 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.9
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.9
In what phase of testing is maraviroc?
Oral maraviroc for use as HIV PrEP is in Phase II testing. Other forms of maraviroc, including an IVR and a gel, are in Phase I testing for HIV prevention.4,5
What are some studies on maraviroc?
Oral Maraviroc for HIV PrEP
HPTN 069/A5305 (NEXT PrEP); NCT01505114
National Institute of Allergy and Infectious Diseases (NIAID)
- Men who have sex with men (MSM) who did not have HIV but were at increased risk for getting HIV through sex
- Women who did not have HIV but were at increased risk for getting HIV infection through sex
The purpose of this study was to compare the safety and tolerability of four different medicine regimens for HIV PrEP. Three of the medicine regimens included the oral form of maraviroc.10
Participants were women who were not infected with HIV.
The purpose of this study was to look at maraviroc concentrations and immune cells in the blood and genital tracts of participants before, during, and after they received maraviroc.11
Fundacio Lluita Contra la SIDA
Participants were MSM who were not infected with HIV.
The purpose of this study was to use rectal mucosa samples from men not infected with HIV and see whether a single dose
of maraviroc could help prevent HIV infection in a laboratory setting.12
In addition, a Phase IV study used rectal and vaginal tissue samples from healthy, HIV-uninfected adults and looked at the effect of a single dose of maraviroc on the samples in a laboratory setting.13
For more details on the studies listed above, see the Health Professional version
Other Forms of Maraviroc for HIV Prevention
Other forms of maraviroc have been or are being studied in Phase I trials.4,5
These include (1) a maraviroc-only IVR, (2) an IVR that contains maraviroc and the investigational drug dapivirine
, and (3) a maraviroc gel that can be administered rectally or vaginally.4,5,14
What side effects might maraviroc cause?
In the HPTN 069 study (NCT01505114), the safety of the three regimens containing oral maraviroc were comparable to the safety of emtricitabine and tenofovir disoproxil fumarate (the HIV medicines that are FDA-approved for PrEP).15
In the entire group of at-risk MSM, side effects that were of moderate severity or greater and that occurred in more than 5% of participants included lower-than-normal blood levels of the electrolyte phosphate (hypophosphatemia) and upper respiratory tract infection. Side effects that were related to the gastrointestinal system or to the kidneys included diarrhea, nausea, vomiting, unintentional weight loss, and increased creatinine. All of these side effects were moderate in severity.15
In the entire group of at-risk women, side effects that were of moderate severity or greater and that occurred in more than 5% of participants included hypophosphatemia, headache, and urinary tract infections. Side effects that were related to the gastrointestinal system or to the kidneys included diarrhea, nausea, vomiting, unintentional weight loss, and increased creatinine. Most of these side effects were moderate in severity.16
Additional information on side effects known to be associated with maraviroc can be found in the FDA-approved Selzentry Full Prescribing Information.3
Where can I get more information about clinical trials studying maraviroc?
More information about maraviroc-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?
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.9
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.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/376348-65-1. Last accessed on August 18, 2016.
- DrugBank. Maraviroc. Available at: http://www.drugbank.ca/drugs/DB04835. Last accessed on August 18, 2016.
- ViiV Healthcare Company. SELZENTRY- maraviroc tablet, film coated: Full Prescribing Information, April 21, 2015. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=46f30ac5-c96b-429e-976d-8c5ee1c0761b. Last accessed on August 18, 2016.
- Clayden P, Collins S, Frick M, et al. HIV i-BASE/Treatment Action Group. 2016 Pipeline Report. July 2016. Available at: http://www.pipelinereport.org/sites/default/files/2016%20Pipeline%20Report%20Full_0.pdf . Last accessed on August 18, 2016.
- International Partnership for Microbicides, Inc. CHARM-03: A Randomized, Open Label, Crossover Phase 1 Safety and Pharmacokinetic Study of Oral Maraviroc and Maraviroc 1% Gel Administered Rectally and Vaginally to HIV-1 Seronegative Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 20, 2015. NLM Identifier: NCT02346084. Available at: https://clinicaltrials.gov/ct2/show/NCT02346084. Last accessed on August 18, 2016.
- Brown KC, Patterson KB, Malone SA, et al. Single and Multiple Dose Pharmacokinetics of Maraviroc in Saliva, Semen, and Rectal Tissue of Healthy HIV-negative Men. J Infect Dis. 2011 May 15; 203(10): 1484–1490. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080897/. Last accessed on August 18, 2016.
- Dumond JB, Patterson KB, Pecha AL, et al. Maraviroc Concentrates in the Cervicovaginal Fluid and Vaginal Tissue of HIV-Negative Women. J Acquir Immune Defic Syndr. 2009 Aug 15; 51(5): 546–553. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751766/. Last accessed on August 18, 2016.
- Massud I, Aung W, Martin A, et al. Lack of Prophylactic Efficacy of Oral Maraviroc in Macaques despite High Drug Concentrations in Rectal Tissues. J Virol. 2013 Aug; 87(16): 8952-61. Available at: http://jvi.asm.org/content/87/16/8952.full. Last accessed on August 18, 2016.
- 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 August 18, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). A Phase II Randomized, Double-Blind, Study of the Safety and Tolerability of Maraviroc (MVC), Maraviroc + Emtricitabine (MVC+FTC), Maraviroc + Tenofovir Disoproxil Fumarate (MVC+TDF), or Tenofovir Disoproxil Fumarate + Emtricitabine (TDF+FTC) For Pre-Exposure Prophylaxis (PrEP) To Prevent HIV Transmission in At-Risk Men Who Have Sex With Men and in At-Risk Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 4, 2012. NLM Identifier: NCT01505114. Available at: https://clinicaltrials.gov/ct2/show/NCT01505114. Last accessed on August 18, 2016.
- Emory University. Exploring HIV Entry Blockade as a Pre-exposure Prophylaxis Strategy in Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 9, 2012. NLM Identifier: NCT01749566. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01749566. Last accessed on August 18, 2016.
- Fundacio Lluita Contra la SIDA. PILOT STUDY OF PROTECTION AGAINST ex Vivo HIV INFECTION IN RECTAL MUCOSA IN HEALTHY VOLUNTEERS AFTER ADMINISTRATION OF MARAVIROC. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 10, 2012. NLM Identifier: NCT01719627. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01719627. Last accessed on August 18, 2016..
- Fox J, Herrera C, Tiraboschi JM, et al. A Phase IV PrEP Study Reveals Limited Ex Vivo Potency of Oral Maraviroc Against HIV-1. Abstract presented at: 22nd Conference on Retroviruses and Opportunistic Infections (CROI); February 23-26, 2015; Seattle, WA. Abstract 86LB. Available at: http://www.croiconference.org/sessions/phase-iv-prep-study-reveals-limited-ex-vivo-potency-oral-maraviroc-against-hiv-1. Last accessed on August 18, 2016. .
- Chen BA, Panther L, Marzinke MA, et al. Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics of Dapivirine and Maraviroc Vaginal Rings: A Double-Blind Randomized Trial. J Acquir Immune Defic Syndr. 2015 Nov 1; 70(3): 242-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26034880. Last accessed on August 18, 2016..
- Gulick R. HPTN 069 / ACTG A5305: Phase II Study of Maraviroc (MVC)-Containing Regimens for HIV PrEP in Men Who Have Sex With Men (MSM). 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2016. Available at: http://www.natap.org/2016/CROI/croi_39.htm. Last accessed on August 18, 2016..
- Gulick RM. HPTN 069 / ACTG A5305 Phase II Study of Maraviroc (MVC)-Containing Regimens for HIV PrEP in U.S. Women. 21st International AIDS Conference (AIDS 2016); July 18-22, 2016; Durban, South Africa. Levin: HPTN 069 / ACTG A5305 Phase II Study of Maraviroc (MVC)-Containing Regimens for HIV PrEP in U.S. Women...."NO new infections....annual incidence rate 0%"; Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2016. Available at: http://www.natap.org/2016/IAC/IAC_15.htm. Last accessed on August 18, 2016.
Last Reviewed: August 18, 2016