Drugs

Maraviroc (HIV prevention)

Maraviroc (HIV prevention)

Other Names: MVC (HIV prevention), Selzentry (HIV prevention) Drug Class: CCR5 Antagonist Molecular Formula: C29 H41 FNO Registry Number: 376348-65-1 (CAS) Chemical Name: Cyclohexanecarboxamide, 4,4-difluoro-N-((1S)-3-((3-exo)-3-(3-methyl-5-(1-methylethyl)-4H-1,2,4-triazol-4-yl)-8-azabicyclo(3.2.1)oct-8-yl)-1-phenylpropyl)- Chemical Class: Phenylpropylamines Organization: ViiV Healthcare Phase of Development: Oral maraviroc for use as HIV pre-exposure prophylaxis is in Phase II development. (Topical microbicide formulations of maraviroc are in Phase I development.) 

(Compound details obtained from ChemIDplus Advanced,1 Antimicrobial Agents and Chemotherapy article,2 Selzentry Full Prescribing Information,3 Treatment Action Group 2017 Pipeline Report,4 and ClinicalTrials.gov5,6)

What is maraviroc?

What is maraviroc?

Maraviroc is an investigational HIV drug that is being studied to prevent HIV infection.4–6 Maraviroc is currently approved to treat HIV infection under the brand name Selzentry.3 

Maraviroc belongs to a group of HIV drugs called CCR5 antagonists.3 CCR5 antagonists work by attaching to the CCR5 co-receptor protein on the surface of the immune cells. When maraviroc attaches to the CCR5 co-receptor, certain strains of HIV—called R5-tropic virus—cannot attach to, enter, or infect the cell.2 This prevents HIV from multiplying and can reduce the amount of HIV in the body.

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 has been studied as a possible medicine for HIV pre-exposure prophylaxis (PrEP). For more information on PrEP, see the AIDSinfo Pre-Exposure Prophylaxis fact sheet.4,7–9

Other forms of maraviroc, including an intravaginal ring (IVR) and a gel, are in Phase I studies for HIV prevention.4,5,10

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. 

Which clinical trials are studying maraviroc?

Which clinical trials are studying maraviroc?

Oral maraviroc for HIV prevention

Study Names: HPTN 069/A5305 (NEXT PrEP); NCT01505114
Phase: II
Status: This study has been completed.
Location: United States and Puerto Rico
Purpose: The purpose of this study was to compare the safety and tolerability of 4 different medicine regimens for HIV PrEP. Three of the medicine regimens included the oral form of maraviroc.6

Study Names: MVC-PrEP; NCT01749566 
Phase: I
Status: This study has been completed.
Location: United States
Purpose: 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

Study Names: MARAVIPREX; NCT01719627 
Phase: I
Status: This study has been completed.
Location: Spain
Purpose: The purpose of this study was to use rectal mucosa samples from men without HIV and see whether a single dose of maraviroc could help prevent HIV infection in a laboratory setting.12
 
Other studies on oral maraviroc for PrEP include a Phase IV study that used rectal and vaginal tissue samples from healthy adults without HIV. The study 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 of this drug summary.

Other forms of maraviroc for HIV prevention 

Other forms of maraviroc have been studied in Phase I trials.4,5,9 These include (1) a maraviroc-only IVR, (2) an IVR that contains maraviroc and the investigational drug dapivirine, (3) an IVR that contains maraviroc and the HIV medicine emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada), and (4) a maraviroc gel that can be administered rectally or vaginally.4,5,9,14

What side effects might maraviroc cause?

What side effects might maraviroc cause?

HPTN 069 (NCT01505114):
In this Phase II study, the safety of the 3 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 group of women, approximately one-third of participants had discontinued study treatment by Week 48 of the study for various reasons.16

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.17

Additional information on side effects known to be associated with maraviroc can be found in the FDA-approved Full Prescribing Information for Selzentry.3

Because maraviroc is still being studied, information on possible side effects of the drug is not complete. As testing of maraviroc continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying maraviroc?

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.

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: Maraviroc. https://chem.nlm.nih.gov/chemidplus/rn/376348-65-1. Accessed August 22, 2018.
  2. Asin-Milan O, Sylla M, El-Far M, et al. Synergistic combinations of the CCR5 inhibitor VCH-286 with other classes of HIV-1 inhibitors. Antimicrob Agents Chemother. 2014;58(12):7565-7569.
  3. ViiV Healthcare Company. Selzentry: full prescribing information, November 2016. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=46f30ac5-c96b-429e-976d-8c5ee1c0761b. Accessed August 22, 2018.
  4. Frick M, Gaudino A, Harrington M, et al. Treatment Action Group. 2017 pipeline report. http://www.pipelinereport.org/sites/default/files/2017%20Pipeline%20Report%20Final.pdf. Accessed August 22, 2018.
  5. 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. https://clinicaltrials.gov/ct2/show/NCT02346084. Accessed August 22, 2018.
  6. 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. https://clinicaltrials.gov/ct2/show/NCT01505114. Accessed August 22, 2018.
  7. 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;203(10):1484-1490.
  8. 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;51(5):546-553.
  9. 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;87(16):8952-8961.
  10. Auritec Pharmaceuticals. Open-label safety and pharmacokinetic study of single (TDF), dual (TDF-FTC), and triple ARV IVR (TDF-FTC-MVC) in healthy women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 4, 2014. NLM Identifier: NCT02431273. https://www.clinicaltrials.gov/ct2/show/NCT02431273. Accessed August 22, 2018.
  11. 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. https://www.clinicaltrials.gov/ct2/show/NCT01749566. Accessed August 22, 2018.
  12. Fundacio Lluita Contra la SIDA. Pilot study of protection against ex vivo HIV infection in rectal mucosa in health volunteers after administration of maraviroc. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 10, 2012. NLM Identifier: NCT01719627. https://www.clinicaltrials.gov/ct2/show/NCT01719627. Accessed August 22, 2018.
  13. 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. http://www.croiconference.org/sessions/phase-iv-prep-study-reveals-limited-ex-vivo-potency-oral-maraviroc-against-hiv-1. Accessed August 22, 2018.
  14. 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;70(3):242-249.
  15. 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. http://www.natap.org/2016/CROI/croi_39.htm. Accessed August 22, 2018.
  16. Gulick RM, Wilkin TJ, Chen YQ, et al. Phase 2 safety and tolerability study of maraviroc-containing regimens to prevent HIV infection in women (HPTN 069/ACTG A5305): a randomized trial. Ann Intern Med. 2017;167(6):384-393.
  17. 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. http://www.natap.org/2016/IAC/IAC_15.htm. Accessed August 22, 2018.

Last Reviewed: August 22, 2018