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We hypothesize that using a potent antiretroviral such as Enfuvirtide during the induction phase of HAART therapy will lead to faster clearance of virus and infected cells, and lower number of minority variant HIV-1 strains.
This is an 48 week Phase 4, open label, randomized, prospective, pilot proof of concept study to evaluate the use of Enfuvirtide in an induction/maintenance treatment model. Patients meeting inclusion criteria will be stratified into two groups according to HIV-1 RNA viral loads (less than 300,000 copies/ml and greater than 300,000 copies/ml). Thereafter, patients will be block randomized (the size of each block will be two patients) into one of two treatment arms.
All patients will receive Efavirenz 600mg once a day, Lamivudine 300 mg once a day, and Tenofovir 300mg once a day. After randomization, one half of the patients will receive no additional treatment, while the other half will receive Enfuvirtide 90mg sq BID until the viral load is <50 x 2 consecutive visits or 12 weeks (whichever comes first).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard Treatment | Active Comparator | Efavirenz 600mg once daily, Lamivudine 300mg once daily and Tenofovir 300mg once daily |
|
| Standard Treatment Plus Enfuvirtide | Experimental | Efavirenz 600mg once daily, Lamivudine 300mg once daily, Tenofovir 300mg once daily and enfuvirtide 90mg subcutaneously twice a day until the viral load is less than 50copies for 2 consecutive visits or 12 weeks (whichever comes first). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enfuvirtide | Drug | subcutaneously twice a day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to viral suppression below 50c/ml. | The study is 48 weeks long and the time to viraL suppression will vary depending on the subject. Or there is the possibility that they do not supress | Individual |
| Measure | Description | Time Frame |
|---|---|---|
| Log viral copy/ml decrease over time during phase 1 and phase 2. | Over the 48 week study period | |
| Development of clinical mutations. | Over the 48 week study period | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ronald B Reisler, MD, MPH | University of Maryland, School of Medicine, Department of Infectious Disease | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland, Institute of Human Virology | Baltimore | Maryland | 21201 | United States |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D000077560 | Enfuvirtide |
| C098320 | efavirenz |
| D019259 | Lamivudine |
| D000068698 | Tenofovir |
| D000068257 | Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination |
| ID | Term |
|---|---|
| D010446 | Peptide Fragments |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D015700 | HIV Envelope Protein gp41 |
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| Efavirenz, lamivudine, and tenofovir | Drug | Efavirenz -600mg once daily, lamivudine- 300mg once daily, and tenofovir 300mg once daily |
|
|
| Development of sub-clinical mutations (minority variants) |
| Over the 48 week study period |
| Viral suppression (below 50c/ml) at 24 and 48 weeks. | At 24 and 48 weeks |
| Time to loss of viral response. Loss of viral response defined as: | Over the 48 week study period |
| Less then 2.0 log decrease in viral load at week 8. | Week 8 |
| Inability to achieve Viral load <50c/ml by week 12. | Week 12 |
| Viral load >50c/ml on 2 consecutive measurements taken 2 weeks apart after viral | Over the 48 week study period |
| suppression <50c/ml has occurred | Over the 48 week study period |
| Rate and quantity of HIV-1 proviral DNA decay. | Over the 48 week study period |
| Safety and tolerability. | Over the 48 week study period |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D014760 | Viral Fusion Proteins |
| D050576 | Membrane Fusion Proteins |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D015488 | HIV Antigens |
| D000956 | Antigens, Viral |
| D014764 | Viral Proteins |
| D054299 | env Gene Products, Human Immunodeficiency Virus |
| D015686 | Gene Products, env |
| D012191 | Retroviridae Proteins |
| D054298 | Human Immunodeficiency Virus Proteins |
| D014759 | Viral Envelope Proteins |
| D015678 | Viral Structural Proteins |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D015224 | Dideoxynucleosides |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010078 | Oxazines |
| D000068679 | Emtricitabine |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |