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

Phase 4

Completed

• Conditions: HIV
• Interventions: Drug: Lopinavir / ritonavir; Drug: 2-3N(t)RTI; Drug: raltegravir

• Registration Number: NCT01513122
• Lead Sponsor: Kirby Institute

Brief 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).

Detailed Description

Not available

Study Timeline

• Study Start: 2010-02
• Study First Submitted: 2012-01-16
• Study First Submitted QC: 2012-01-19
• Study First Posted: 2012-01-20
• Primary Completion: 2012-09
• Study Completion: 2013-08
• Results First Submitted: 2013-12-01
• Results First Submitted QC: 2013-12-01
• Results First Posted: 2014-01-17
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-25
• Last Update Posted: 2019-09-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 210

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI	2-3N(t)RTI	LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTI
Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI	Lopinavir / ritonavir	LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTI
Arm 2. Lopinavir /ritonavir + raltegravir	Lopinavir / ritonavir	-
Arm 2. Lopinavir /ritonavir + raltegravir	raltegravir	-

Primary Outcome Measures

Name	Time	Method
Mean Bone Mineral Density Changes From Baseline to 48 Weeks as Measured by DXA Scan	48 weeks
Mean Limbs Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan	48 weeks

Secondary Outcome Measures

Name	Time	Method
Mean Glucose Changes From Baseline to 48 Weeks	48 weeks
Mean Total Body Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan	48 weeks
Mean Triglycerides Changes From Baseline to 48 Weeks	48 weeks
Mean Total Cholesterol Changes From Baseline to 48 Weeks	48 weeks

Trial Locations

Locations (7)

Desmond Tutu HIV Foundation; 🇿🇦 Cape Town, South Africa

CEADI; 🇦🇷 Buenos Aires, Argentina

HIV-NAT Program on AIDS - Thai Red Cross; 🇹🇭 Bangkok, Thailand

Chris Hani Baragwanath Hospital; 🇿🇦 Soweto, South Africa

JOSHA Research; 🇿🇦 Bloemfontein, South Africa

YRGCare Medical Centre; 🇮🇳 Chennai, India

University of Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Malaysia