Bone and Body Comp: A Sub Study of the SECOND-LINE Study

Kirby Institute

Status and phase: Completed; Phase 4

Conditions: HIV

Treatments: Drug: 2-3N(t)RTI; Drug: raltegravir; Drug: Lopinavir / ritonavir

Study type: Interventional

Funder types: Other

Identifiers

NCT01513122

2L body comp sub-study

Details and patient eligibility

About

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).

Enrollment: 210 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

210 participants in 2 patient groups

Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI

Active Comparator group

Description:

LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTI

Treatment:

Drug: Lopinavir / ritonavir

Drug: 2-3N(t)RTI

Arm 2. Lopinavir /ritonavir + raltegravir

Active Comparator group

Treatment:

Drug: raltegravir

Drug: Lopinavir / ritonavir