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

• Log viral copy/ml decrease over time during phase 1 and phase 2. [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: No ]
• Development of clinical mutations. [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
• Development of sub-clinical mutations (minority variants) [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
• Viral suppression (below 50c/ml) at 24 and 48 weeks. [ Time Frame: At 24 and 48 weeks ] [ Designated as safety issue: Yes ]
• Time to loss of viral response. Loss of viral response defined as: [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
• Less then 2.0 log decrease in viral load at week 8. [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
• Inability to achieve Viral load <50c/ml by week 12. [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]
• Viral load >50c/ml on 2 consecutive measurements taken 2 weeks apart after viral [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
• suppression <50c/ml has occurred [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
• Rate and quantity of HIV-1 proviral DNA decay. [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
• Safety and tolerability. [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]

• Log viral copy/ml decrease over time during phase 1 and phase 2.
• Development of clinical mutations.
• Development of sub-clinical mutations (minority variants)
• Viral suppression (below 50c/ml) at 24 and 48 weeks.
• Time to loss of viral response. Loss of viral response defined as:
• Less then 2.0 log decrease in viral load at week 8.
• Inability to achieve Viral load <50c/ml by week 12.
• Viral load >50c/ml on 2 consecutive measurements taken 2 weeks apart after viral
• suppression <50c/ml has occurred
• Rate and quantity of HIV-1 proviral DNA decay.
• Safety and tolerability.

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).

• Drug: Enfuvirtide
  subcutaneously twice a day
  Other Name: Fuzeon (T-20)
• Drug: Efavirenz, lamivudine, and tenofovir
  Efavirenz -600mg once daily, lamivudine- 300mg once daily, and tenofovir 300mg once daily
  Other Name: Atripla, Epivir and Viread

• Active Comparator: Standard Treatment
  Efavirenz 600mg once daily, Lamivudine 300mg once daily and Tenofovir 300mg once daily
  Intervention: Drug: Efavirenz, lamivudine, and tenofovir
• Experimental: Standard Treatment Plus Enfuvirtide
  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).
  Interventions:

  • Drug: Enfuvirtide
  • Drug: Efavirenz, lamivudine, and tenofovir

Inclusion Criteria:

1. Age: 18 to 70 years of age.
2. Sex: Male or Female.
3. Documented HIV-1 seropositive by Western Blot, Elisa, or HIV-1 viral load.
4. Naïve to HAART.
5. Viral load >100,000c/ml.
6. CD4<200c/ml.
7. Volunteers must be willing and able to provide written informed consent to participate in the study.
8. Available for at least 48 weeks of follow-up.

Exclusion Criteria:

1. 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.
2. 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.
3. Renal insufficiency (Estimated Creatinine clearance of <60ml/min.)
4. Patients with malabsorption or severe chronic diarrhea for more than 30 days.
5. Inability to consume adequate oral intake (defined as inability to eat at least 1 meal per day).
6. Current treatment for malignancy other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
7. Any other medical condition which, in the opinion of the investigator, might interfere with completion of the study or evaluation of the results.
8. Pregnancy or breastfeeding
9. In a female capable of child bearing, unwillingness to use effective barrier contraception or abstinence
10. Patient who is currently receiving an experimental medication.