Efficacy and Safety of Raltegravir (RAL) in Treatment-experienced HIV-1 Infected Adult Chinese Patients

• the safety and tolerability of RAL 400 mg b.i.d. in combination with optimized background therapy (OBT), assessed by review of the accumulated safety data in HIV-infected adult patients. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  

• antiretroviral activity of RAL 400 mg b.i.d. in combination with OBT as measured by change at week 24 in viral load from baseline, increase of CD4+ T lymphocytes compared to baseline [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  

An open, prospective, uncontrolled pilot study to evaluate the efficacy and safety of raltegravir in treatment-experienced HIV-1 infected adult patients who have failed the previous antiretroviral treatment due to drug resistance or drug intolerance.

1. Patients Enrollment:

   HIV-infected patients aged over 18 who have failed previous antiretroviral treatment with multi-drug resistant or with multi-drug intolerance are eligible. And at least 50 subjects are to be concluded in the trial.

   ⅰ) The diagnostic criteria of HIV/AIDS refer to guidelines for diagnosis and treatment of HIV/AIDS in China(2005).

   ⅱ) Treatment failure will be defined as follows: (i): HIV viral load has decreased by less than 1 log copies/ml in patients with 8 weeks of HAART, or (ii) HIV viral load is still detectable after 6 months of HAART;or (iii) reappearance of a detectable viral load after HAART has led to undetectable viral load.

   ⅲ) The definition of drug resistance is based on a genotypic resistance test.

   ⅳ) Drug intolerance involves all the serious antiretroviral drug related adverse events, such as AZT related bone marrow suppression, NVP or EFV related serious liver damage and allergic reaction, d4T related lactic acidosis, pancreatitis and peripheral neuritis, etc.

2. Patients enrolled in the study sign consent form.

3. Antiretroviral regimen for the subjects:

   The patients enrolled in the study accept a treatment regimen of RAL 400 mg twice daily plus OBT (optimized background therapy), which is selected on the basis of the patient's antiretroviral treatment history, results from all available genotypic resistance tests, previous or current laboratory abnormalities and intolerance to other antiretroviral drugs, and shall, if possible, contain two anti-retroviral drugs fully active against the patient's virus by genotype.

4. Data collection:

   For each patient, detection of HIV viral load and CD4+ T lymphocyte count is done at screening, and at weeks 4, 12, 24 and 48. The safety profile of RAL is monitored according to patients' complaints and the results of physical and laboratory examinations. Plasma HIV RNA viral loads are determined by HIV-1 Quantiplex(bDNA) assay approved by FDA. CD4+ T lymphocytes are counted with flow cytometry. Any drug-related adverse events that patients experience during treatment will be recorded, such as nausea, vomiting, abdominal pain, abodominal distension, diarrhea, fever, headache, dizzy, fatigue etc. Laboratory examinations cover blood, urine and stool routine, liver and renal function, electrolytes, blood glucose, blood lipid, electrocardiogram etc.

5. Endpoints of study:

The primary endpoint is the the safety and tolerability of RAL 400 mg b.i.d. in combination with OBT, assessed by review of the accumulated safety data in HIV-infected adult patients. The secondary endpoint is antiretroviral activity of RAL 400 mg b.i.d. in combination with OBT as measured by change at week 24 in viral load from baseline, increase of CD4+ T lymphocytes compared to baseline and proportions of patients with: viral load less than 400 copies/ml; viral load less than 50 copies/ml; and a reduction in viral load from baseline exceeding 1.0 log10 copies/ml.