Raltegravir-based Antiretroviral Therapy for Resistant HIV-1 Infection

Study Overview
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Brief Summary
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This study is to evaluate the safety and efficacy of RAL-based regimen in treatment-experienced patients with resistant HIV infection

Detailed Description
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In our study, both efficacy and safety of raltegravir(RAL)-based therapy will be assessed. 300 treatment-experienced patients with drug-resistant HIV will be randomized to two arms (2:1). Group A (n=200) will be assigned with RAL-based regimen (RAL+TDF+LPV/r).Group B (n=100) will be assigned with current second-line regimen in China (3TC+TDF+LPV/r). Both virological and immunological profiles and responses at baseline and at week 4, 8, 12, 24, 36, and 48 will be evaluated. This study will be the first large-scale, multicenter, randomized, prospective RAL-based therapy study in China for HIV/AIDs patients. The result will provide proves for further practical antiviral therapy for China or other resource-limiting countries.

Official Title
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Raltegravir-based Antiretroviral Therapy for Resistant HIV-1 Infection in China

Conditions
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AIDS/HIV PROBLEM

Intervention / Treatment
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* Drug: RAL+TDF+LPV/r
* Drug: 3TC+TDF+LPV/r


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18-65 years HIV seropositive and confirmed by western blot have taken first line antiretroviral therapy for over one year and have any one of the criteria listed below (viral load of all the patients meeting these criteria should be confirmed at PUMCH laboratory) Viral load more than 400 copies/ml Viral rebound (confirmed by HIV RNA more than 400 copies/ml after virologic suppression) When viral load cannot be monitored, patients experience immunologic failure who meet at least one of the criteria listed below will be enrolled: CD4 count equal to or lower than baseline level with first-line therapy,on two occasions over three months apart CD4 count with 50 percentage fall from the on-treatment peak value persistent CD4 count levels less than 100 cells/μl after over one-year antiretroviral therapy Exclusion Criteria: Previous use of protease inhibitors Previous use of integrase inhibitors Pregnancy and breastfeeding poor compliance and drug interaction, opportunistic infections or malignancy at recruitment; or opportunistic infections within three months but still unstable within 14 days prior to recruitment HBsAg positive patients with the any of the following test results during screening for inclusion: WBC count<2000/μl, neutrophil count<1000/μl, Hb<9g/dl, platelet count<75000/μl, serum creatinine>1.5 ULN, transaminases or alkaline phosphatase >3 ULN, total bilirubin>2 ULN, serum creatinine kinase>2 ULN CCr<60 ml/min Current intravenous drug use Severe neuropathy or mental disorder history of alcohol abuse and unable to withdrawal Severe peptic ulcer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: RAL +TDF+ LPV/r<br>Arm A: RAL +TDF+ KELETRA(LPV/r) Group A will be assigned with RAL+TDF+LPV/r. | Drug: RAL+TDF+LPV/r<br>* Group A will be assigned with RAL-based regimen (RAL+TDF+LPV/r).<br>|
| Active Comparator: 3TC+ TDF+LPV/r<br>Arm B: 3TC+ TDF+KELETRA(LPV/r) Group B will be assigned with 3TC+TDF+LPV/r | Drug: 3TC+TDF+LPV/r<br>* Group B will be assigned with 3TC+TDF+LPV/r<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with HIV-1 RNA < 400 copies/mL at week 48 |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with HIV-1 RNA < 40 copies/mL at week 48 |  | 48 weeks | 
| Change from baseline in CD4 count at week 48 |  | Baseline and 48 weeks | 
| Incidence of adverse events and laboratory abnormalities in the two treatment arms from baseline to week 48 |  | through week 48 |