A Study to Evaluate of the Efficacy of Enfuvirtide During the Induction Phase of Therapy

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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Viral Decay Kinetics During Induction Therapy With or Without the Use of Enfuvirtide in HAART-naÃ-ve Patients With Advanced HIV

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Enfuvirtide
* Drug: Efavirenz, lamivudine, and tenofovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 to 70 years of age. Sex: Male or Female. Documented HIV-1 seropositive by Western Blot, Elisa, or HIV-1 viral load. Naïve to HAART. Viral load >100,000c/ml. CD4<200c/ml. Volunteers must be willing and able to provide written informed consent to participate in the study. Available for at least 48 weeks of follow-up. Exclusion Criteria: Volunteers with an acute and clinically significant medical event as determined by the investigator to result in a life expectancy less then 12 months despite ART. Volunteers with current psychiatric illness, alcohol abuse or illicit drug use that in the opinion of the Principal Investigator may interfere with patient's ability to comply with protocol requirements. Renal insufficiency (Estimated Creatinine clearance of <60ml/min.) Patients with malabsorption or severe chronic diarrhea for more than 30 days. Inability to consume adequate oral intake (defined as inability to eat at least 1 meal per day). Current treatment for malignancy other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. Any other medical condition which, in the opinion of the investigator, might interfere with completion of the study or evaluation of the results. Pregnancy or breastfeeding In a female capable of child bearing, unwillingness to use effective barrier contraception or abstinence Patient who is currently receiving an experimental medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Treatment<br>Efavirenz 600mg once daily, Lamivudine 300mg once daily and Tenofovir 300mg once daily | Drug: Efavirenz, lamivudine, and tenofovir<br>* Efavirenz -600mg once daily, lamivudine- 300mg once daily, and tenofovir 300mg once daily<br>* Other names: Atripla, Epivir and Viread;|
| Experimental: Standard Treatment Plus Enfuvirtide<br>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). | Drug: Enfuvirtide<br>* subcutaneously twice a day<br>* Other names: Fuzeon (T-20);Drug: Efavirenz, lamivudine, and tenofovir<br>* Efavirenz -600mg once daily, lamivudine- 300mg once daily, and tenofovir 300mg once daily<br>* Other names: Atripla, Epivir and Viread;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 |