Phase 1 Pilot Study of an ART Bridging Regimen in Highly Experienced Patients Unable to Achieve Viral Suppression

Bridge is a pilot, single-arm, open-label, study to assess the ability of 3 FDA approved anti-retroviral drugs to decrease replication capacity of HIV virus in order to stabilize CD4 cell count and HIV RNA viral loads . All subjects will be prescribed the three-drug combination of lamivudine (3TC) + tenofovir disoproxil fumarate (TDF) + nelfinavir (NLV)The "Bridge Study" is a pilot, study to assess the ability of 3 FDA approved anti-retroviral drugs to decrease replication capacity of HIV virus in order to stabilize CD4 cell count and HIV RNA viral loads. All subjects will receive the three-drug combination of lamivudine (3TC)+tenofovir disoproxil fumarate(TDF)+nelfinavir (NLV)

The study will enroll 12 subjects for a 48 week study. Major entry criteria include: HIV+ Men and women 18 years of age who are currently failing antiretroviral(ARV)therapy with an HIV-1 RNA VL > 10,000 and have failed multiple treatment regimens due to resistance and/or intolerance. Genotype must demonstrate resistance to 3 major classes of ARV's - PI's, NNRTI's, and NRTI's.

Inclusion criteria

• Men and women age > 18 years of age.
• Ability and willingness to give written informed consent.
• HIV-1 infection as documented by any licensed ELISA test kit and confirmed by either Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA prior to study entry.
• Patient failed multiple treatment regimens due to development of viral resistance/and or intolerance.
• Patient's provider feels that patient has exhausted currently available treatment options and that it is highly unlikely that a regimen (including one that contains T-20) could be constructed that would result in sustained virologic suppression at this time.
• Evidence of MDR virus (broad 3 class resistance) based on the results of the MDR-HIV qualifying screening genotypic resistance test or a history of a previous genotypic resistance test.
• The following screening laboratory values obtained within 30 days prior to study entry:

• HIV-1 RNA or BDNA > 10,000 copies/mL

Exclusion criteria

• Active drug or alcohol abuse or dependence which, in the opinion of the investigator, would interfere with adherence to study requirements.
• History of any illness that, in the opinion of the study investigators, might confound the results of the study or pose additional risk in administering study drugs to the subject.
• Acute therapy for a serious infection or other serious medical illnesses that are potentially life threatening and require systemic therapy and/or hospitalization.

NOTE: Subjects with a serious infection or serious medical illness must complete acute therapy at least 7 days prior to study entry. Subjects with all other infections or medical illnesses (e.g., vaginitis, folliculitis, bronchitis, pharyngitis, thrush) must receive appropriate therapy prior to study entry (no time restriction).

• Significant Renal Insufficiency - calculated creatinine clearance < 50
• Upon reviewing medication history and genotypic resistance testing, study investigators feel that would be inappropriate to enroll patient in this protocol.