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.
Monomeric DAPTA (mDAPTA) is an investigational drug that was once being studied for its ability to eliminate HIV infection that persists despite treatment with antiretroviral therapy (ART). Currently, ART can reduce the level of HIV in the blood to an undetectable level, but it can't eliminate HIV entirely from the body.4,5
mDAPTA is a newer, modified form of an older investigational drug called peptide T. Both mDAPTA and peptide T belong to a class (group) of HIV drugs called entry and fusion inhibitors.2 Entry and fusion inhibitors block HIV from getting into and infecting certain cells of the immune system. This prevents HIV from multiplying and can reduce the amount of HIV in the body.
mDAPTA works by attaching to one of two proteins on the surface of the immune cells. These proteins are called the CCR5 and CXCR4 co-receptors. mDAPTA attaches to the CCR5 co-receptor. When mDAPTA attaches to the CCR5 co-receptor, certain strains of HIV—called R5-tropic virus—cannot attach to, enter, or infect the cell.6
mDAPTA is currently being studied to treat progressive multifocal leukoencephalopathy (PML). PML is a viral infection of the central nervous system (brain and spinal cord). PML can occur in people with a weakened immune system, including people with advanced HIV infection or AIDS.7
The main component of mDAPTA is peptide T. Peptide T was an investigational drug that was previously studied to test its ability to reduce the amount of HIV in the body and bolster the immune system. The drug’s effect on HIV-associated cognitive impairment was also studied. (Cognitive impairment is when people have trouble remembering, learning new things, concentrating, or making decisions that affect their everyday lives.)5,8,9
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.8
In most cases, an investigational drug must be proven safe and effective 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.8
Monomeric DAPTA (mDAPTA) has been studied in Phase II clinical trials for eliminating HIV infection that persists despite treatment with antiretroviral therapy (ART).2,4
Peptide T (base compound of monomeric DAPTA [mDAPTA])
Study Name: Not available
Phase: Not available
Location: United States (San Francisco)
Participants: HIV-infected people who had been infected with HIV for many years and who had viral loads (the amount of HIV in the blood) that were relatively unchanged over three weekly measurements. Participants included people who had never taken HIV medicines before (treatment-naïve) and people who had taken HIV medicines before (treatment-experienced).
Purpose: The purpose of this study was to examine the ability of peptide T to reduce viral load, improve immune function, and reduce HIV replication in blood monocytes (a type of white blood cell that can be infected by HIV).
Study Design: Some of the participants received only peptide T, and the other participants received peptide T along with antiretroviral therapy (ART). Peptide T was given through the nose (intranasally) three times a day for up to 32 weeks.
Study Name: NCT00000392
Location: United States (California and Florida)
Participants: HIV-infected people with cognitive impairment (trouble with memory, language, thinking, judgment). Participants were required either to have not used HIV medicines within 4 weeks of starting the study or to have had their HIV infection under control with HIV medicines for at least 12 weeks before starting the study.
Purpose: The purpose of this study was to see whether peptide T could improve the cognitive function (such as memory, language, and thinking) of HIV-infected people with cognitive impairment.
Study Design: Participants were given either peptide T or placebo intranasally three times a day for 6 months. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) Study participants’ cognitive function was assessed by various tests, such as tests on verbal fluency, abstract thinking, and memory.
NOTE: During this study, samples of some participants’ blood and cerebrospinal fluid (CSF) were taken at the beginning of the study and again after 6 months and then were frozen and stored. At a later time, investigators analyzed the stored samples to see if peptide T was able to reduce viral load. Results showed that peptide T had a minimal effect on reducing viral load in the blood, but did not have any effect in reducing viral load in the CSF. Researchers noted that this analysis had certain limitations that may have impacted the results. Any results that came out of this analysis would need to be confirmed in future trials.12
mDAPTA (the modified version of peptide T)
Study Name: NCT00951743
Location: United States (Washington DC)
Participants: HIV-infected, treatment-experienced individuals
Purpose: The purpose of this study was to look at the ability of mDAPTA to eliminate HIV that is resistant to current HIV medicines and that remains “resting” in certain immune cells. Although these HIV-infected immune cells may be inactive, they can begin to produce HIV at a later point.
Study Design: At the start of the study, participants had to have been on ART for at least 6 months and have suppressed viral loads. During the study, participants were given mDAPTA twice daily intranasally.
In the first study of peptide T described above, there were no side effects associated with peptide T use among the 11 participants.
In the Phase II cognitive function study, investigators determined that no "clinically significant" side effects occurred. There were, however, some cases of mood disturbance and rash in the peptide T group that were considered either severe and/or life-threatening in intensity. (Investigators report that some of these cases may not have been caused by peptide T use.) Other side effects that occurred in the peptide T group included nasal congestion, abnormal amounts of protein in the urine, and higher than normal amounts of a certain type of white blood cell.8,9 (A period of time after these studies were done, peptide T was reformulated as monomeric DAPTA [mDAPTA].)
Because mDAPTA is still being studied, information on possible side effects of the drug is not complete. As testing of mDAPTA continues, additional information on possible side effects will be gathered.
More information about research studies related to monomeric DAPTA (mDAPTA) 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.
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.10
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.
Last Reviewed: June 17, 2015