A Trial of 2 Options for Second Line Combination Antiretroviral Therapy Following Virological Failure of a Standard Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)+2N(t)RTI First Line Regimen
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: raltegravir; 2N(t)RTI; Ritonavir-boosted lopinavir
Intervention description: 400 mg raltegravir tablet taken every 12 hours; 2N(t)RTIs as prescribed; 2 heat-stable tablets of ritonavir-boosted lopinavir taken every 12 hours
Intervention MeSH terms: Ritonavir; Lopinavir; Raltegravir Potassium
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 558.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: second line therapy; combination antiretroviral therapy; first-line failure; AIDS; treatment experienced

Summary:

      The investigators hypothesize that following virological failure of a standard NNRTI+2N(T)RTI
      regimen second-line antiretroviral therapy consisting of ritonavir-boosted lopinavir and
      2N(T)RTIs will offer comparable efficacy to that provided by ritonavir-boosted lopinavir and
      raltegravir.

      The study will be conducted for 96-weeks with the primary endpoint analyzed after 48-weeks.

      The primary endpoint is virological: a comparison of virological suppression in plasma < 200
      copies/mL between the randomized arms after 48 weeks.

      Secondary and exploratory endpoints include virological, immunological, safety, clinical,
      metabolic, drug adherence, drug resistance and quality of life.
    

Eligibility criteria:

        Inclusion Criteria:

          1. HIV-1 positive by licensed diagnostic test

          2. Aged 16 years or older (or minimum age as determined by local regulations or as legal
             requirements dictate)

          3. Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for
             at least 24 weeks

          4. No change in antiretroviral therapy within 12 weeks prior to screening

          5. Failed first-line NNRTI + 2N(t)RTI combination therapy according to virological
             criteria defined by two consecutive (at least 7 days apart) HIV RNA results of greater
             then 500 copies/mL

          6. No prior or current exposure to HIV protease inhibitors and/or HIV integrase
             inhibitors

          7. Able to provide written informed consent

        Exclusion Criteria:

          1. The following laboratory variables:

               -  absolute neutrophil count (ANC) < 500 cells/microlitres

               -  hemoglobin < 7.0 g/decilitres

               -  platelet count < 50,000 cells/microlitres

               -  ALT great than 5 x ULN

          2. Pregnant or nursing mothers

          3. Participants with active viral hepatitis B infection defined by the presence in serum
             of hepatitis B surface antigen

          4. Use of immunomodulators within 30 days prior to screening

          5. Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride,
             pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine,
             astemizole, terfenadine, vardenafil, and St. John's wort)

          6. Intercurrent illness requiring hospitalization

          7. Active opportunistic disease not under adequate control in the opinion of the site
             Principal Investigator

          8. Participants with current alcohol or illicit substance abuse that in the opinion of
             the site Principal Investigator might adversely affect participation in the study

          9. Participants deemed by the site Principal Investigator unlikely to be able to remain
             in follow-up for the protocol-defined period