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 AIDS
info What is an Investigational HIV Drug? fact sheet.
What is losartan?
Losartan (brand name: Cozaar) is a drug that has been approved by FDA for treating high blood pressure and kidney damage caused by diabetes. It can also help reduce the risk of stroke in certain people.6 Losartan is currently being studied to see if it can be effective as part of a strategy to treat or cure HIV infection.4,5,7
As an investigational therapy, losartan belongs to a class (group) of drugs called antifibrotics.2 Antifibrotics are medicines that can reduce tissue scarring in the body (called fibrosis).8
HIV infection can overwork the body’s immune system, leading to fibrosis in lymphoid tissues. (Lymphoid tissues are a part of the immune system that help to fight infection.) Fibrosis in lymphoid tissues may:
- Damage CD4 cells and make it difficult to restore CD4 counts to normal levels, even in people who are on antiretroviral therapy (ART).
(A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function. ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from replicating.)
- Contribute to the persistence of latent HIV reservoirs in the body.
(latent HIV reservoirs are "resting" CD4 cells or other cells that are infected with HIV but are not actively producing HIV in the body. Because ART does not work against HIV that’s hidden in latent reservoirs, these reservoirs are one of the main obstacles to curing HIV infection.)8-11
By reducing fibrosis, losartan could potentially improve the health of the immune system and reduce the size of the latent HIV reservoir in the body.4,7,8,10,11
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.12
- 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.12
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.12
In what phase of testing is losartan?
Losartan is currently being studied in Phase II clinical trials.4,5
What are some studies on losartan?
Study Name: NCT01852942
Sponsor: University of Minnesota - Clinical and Translational Science Institute
Phase: II
Location: United States
Participants:
- The study involves HIV-infected adults who have previously taken HIV medicines (called treatment-experienced).
- The participants will all be on stable ART at the start of the study.
- Study participants will have CD4 counts of 200 to 600 cells/mm3 and viral load levels (the amount of HIV in a blood sample) of less than 50 copies/mL for 6 months before entering the study.
Purpose: The purpose of this study is to determine if losartan can reduce fibrosis in lymphoid tissues, calm an overactive immune system, improve immune system recovery, and decrease the size of the latent HIV reservoir in the body. The study will also assess losartan’s safety.4
For more details on this study, see the Health Professional version.
Study Name: LIFE-HIV trial; NCT02049307
Sponsor: Minneapolis Medical Research Foundation
Phase: II
Location: United States
Participants:
- The study involves HIV-infected, treatment-experienced adults who are 50 years of age or older.
- Participants have received ART continuously for at least 2 years.
- Participants will have a viral load of less than 200 copies/mL for at least 1 year before entering the study and CD4 cell counts of less than 600 cells/mm3.
Purpose: The purpose of this study is to determine how well losartan reduces inflammation and fibrosis to improve immune system recovery.5,7
For more details on this study, see the Health Professional version.
Study Name: NCT01529749
Sponsor: Felipe Garcia
Phase: IV
Location: Spain
Participants:
- The study involved HIV-infected, treatment-experienced adults who were receiving a combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate as ART at the start of the study.
- The participants were virologically suppressed, with a viral load of less than 37 copies/mL for at least 48 weeks and CD4 cell counts of at least 250 cells/mm3.
Purpose: The purpose of this study was to evaluate the effect of losartan on fibrosis in lymphoid tissues. The study also looked at whether the drug could decrease risk factors of inflammation and cardiovascular disease.13,14
For more details on this study, see the Health Professional version.
What side effects might losartan cause?
Side effects have not yet been reported in the clinical trials that use losartan to treat HIV.
Side effects that are already known to be associated with losartan are described in the FDA-approved Cozaar Full Prescribing Information.6
Because losartan is still being studied, information on possible side effects of the drug is not complete. As testing of losartan continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying losartan?
More information about losartan-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.
I am interested in participating in a clinical trial of losartan. 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.12
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
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/114798-26-4. Last accessed on July 7, 2016.
- Treatment Action Group website. Research Toward a Cure Trials. Available at: http://www.treatmentactiongroup.org/cure/trials. Last accessed on July 7, 2016.
- DrugBank. Losartan. Available at: http://www.drugbank.ca/drugs/DB00678. Last accessed on July 7, 2016.
- University of Minnesota - Clinical and Translational Science Institute. Reversing Tissue Fibrosis to Improve Immune Reconstitution in HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 20, 2012. NLM Identifier: NCT01852942. Available at: https://clinicaltrials.gov/ct2/show/NCT01852942. Last accessed on July 7, 2016.
- Minneapolis Medical Research Foundation. Losartan to Reduce Inflammation and Fibrosis Endpoints in HIV Trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 27, 2014. NLM Identifier: NCT02049307. Available at: https://clinicaltrials.gov/ct2/show/NCT02049307. Last accessed on July 7, 2016.
- Merck Sharp & Dohme Corp. COZAAR- losartan potassium tablet, film coated: Full Prescribing Information, 2015. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ac32c20-169d-475a-fc8a-934f758d6ab0. Last accessed on July 7, 2016.
- National Institute of Allergy and Infectious Diseases. HIV and Emerging Infectious Diseases Program: LIVE-HIV Study. Available at: https://www.niaid.nih.gov/volunteer/hivandinfectious/hivstudies/Pages/life-hiv.aspx. Last accessed on July 7, 2016.
- Zeng M, Southern PJ, Reilly CS, et al. Lymphoid Tissue Damage in HIV-1 Infection Depletes Naive T Cells and Limits T Cell Reconstitution after Antiretroviral Therapy. PLoS Pathog. 2012 Jan; 8(1): e1002437. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252371/. Last accessed on July 7, 2016.
- Zeng M, Smith AJ, Wietgrefe SW, et al. Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. J Clin Invest. 2011 Mar 1; 121(3): 998–1008. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049394/. Last accessed on July 7, 2016.
- Douek DC. Immune activation, HIV persistence, and the cure. Top Antivir Med. 2013 Sep-Oct;21(4):128-32. Available at: https://www.iasusa.org/sites/default/files/tam/21-4-128.pdf. Last accessed on July 7, 2016.
- Hatano H. Immune activation and HIV persistence: considerations for novel therapeutic interventions. Curr Opin HIV AIDS. 2013 May;8(3):211-6. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041488/. Last accessed on July 7, 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 July 7, 2016.
- Felipe Garcia. Effects of Losartan and Antiretroviral Regimen Containing Raltegravir in Fibrosis Inflammation. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 8, 2012. NLM Identifier: NCT01529749. Available at: https://clinicaltrials.gov/ct2/show/NCT01529749. Last accessed on July 7, 2016.
- Torres B, Guardo AC, Caballero M, et al. Effects of Losartan on Lymphoid Tissue Fibrosis, Markers of Inflammation and Cardiovascular Risk in Virologically Supressed HIV Patients After 48 weeks. Poster presented at: 8th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment & Prevention; July 19-22, 2015; Vancouver, Canada. Poster MOPEA027. Available at: http://pag.ias2015.org/PAGMaterial/eposters/1653.pdf. Last accessed on July 7, 2016.
Last Reviewed: July 12, 2016
