Bone and Body Comp: A Sub Study of the SECOND-LINE Study
Condition: HIV
Intervention: Lopinavir / ritonavir; 2-3N(t)RTI; raltegravir
Intervention description: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily; raltegravir 400mg 1 tablet twice daily.
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: 210.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No

Summary:

      The use of anti HIV drugs (ART), and in particular a class of drugs known as nucleoside
      reverse transcriptase inhibitors (N(t)RTI), has been associated with changes in body fat and
      in particular loss of peripheral fat in the limbs. Low bone mineral density and osteoporosis
      are also common in HIV-infected patients. There appears to be some association between ART
      and bone loss, but this is poorly understood and requires further research. The SECOND-LINE
      study provides an opportunity to examine if a new anti-HIV drug (raltegravir) can result in
      greater increase in limb fat than a drug regimen containing N(t)RTI, which is currently
      standard of care. This study also provides an opportunity to examine if additional bone loss
      occurs with the second regimen of anti-HIV drugs and whether non-N(t)RTI regimens of ART used
      in second line therapy result in more or less bone loss than use of other classes of anti-HIV
      drugs such as protease inhibitors or N(t)RTI combinations.

      It is hypothesized that subjects randomised into Raltegravir arm will demonstrate greater
      increases in limb fat and smaller reductions in bone density at the proximal femur over 48
      weeks than those randomised into the control arm (LPV/r + 2-3N(t)RTIs).
    

Eligibility criteria:

        Second-Line main study identifier: NCT00931463

        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 ≥
             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 (≥7 days apart) HIV RNA results of > 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/µL

               -  hemoglobin < 7.0 g/dL

               -  platelet count < 50,000 cells/µL

               -  ALT > 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 hospitalisation

          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