Antiretroviral Therapy Intensification With Raltegravir or Addition of Hyper-immune Bovine Colostrum in HIV-1 Infected Patients With Suboptimal CD4+ T Cell Response (CORAL)

A research study to measure the effect on CD4 counts of adding to current anti-retroviral regimen raltegravir with or without hyper-immune bovine colostrum.

The primary objective of this study is to measure the effect on CD4+ T cell outcome as measured by the mean time weighted CD4+ T cell count change over 24 weeks of two interventions: (I) cART intensification with raltegravir and (II) cART combined with hyper-immune bovine colostrum in HIV-1 infected individuals who have failed to achieve a CD4+ T cell count greater than 350 cells/µL despite persistent HIV plasma viraemia below 50 copies/mL on cART.

Eligible patients will be randomised to one of four arms. I. Raltegravir + hyper-immune bovine colostrum placebo II. Raltegravir placebo + hyper-immune bovine colostrum III. Raltegravir + hyper-immune bovine colostrum IV. Raltegravir placebo + hyper-immune bovine colostrum placebo

• Drug: Raltegravir
  Tablets, 400mg, twice daily
  Other Name: raltegravir
• Drug: Hyper-immune Bovine Colostrum
  Tablet, 1800mg, twice daily
  Other Name: Hyper-immune Bovine Colostrum
• Other: raltegravir placebo
  One tablet, twice daily
  Other Name: placebo
• Other: Hyper-immune Bovine Colostrum placebo
  Three tablets twice daily
  Other Name: Hyper-immune Bovine Colostrum placebo
• Drug: raltegravir and hyper-immune bovine colostrum
  400mg twice daily raltegravir and 1800mg twice daily of hyper-immune bovine colostrum
  Other Name: Raltegravir + hyper-immune bovine colostrum

• Experimental: Raltegravir, bovine colostrum
  Raltegravir and hyper-immune bovine colostrum
  Intervention: Drug: raltegravir and hyper-immune bovine colostrum
• Experimental: Hyper-immune bovine colostrum
  Hyper-immune bovine colostrum and Raltegravir placebo
  Intervention: Drug: Hyper-immune Bovine Colostrum
• Experimental: Raltegravir
  Raltegravir and Hyper-immune Bovine Colostrum Placebo
  Intervention: Drug: Raltegravir
• Placebo Comparator: Placebo
  Raltegravir placebo and hyper-immune bovine colostrum placebo
  Interventions:

  • Other: raltegravir placebo
  • Other: Hyper-immune Bovine Colostrum placebo

Inclusion Criteria:

• Documented HIV-1 infection
• Age >18 years
• Signed informed consent
• Receiving combination ART (cART) for at least 12 months with a stable cART regimen for a minimum of 6 months. A formulation change or modification of dosage schedule is acceptable (for example ritonavir - boosted lopinavir capsules for tablets, abacavir (ABC) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC) as single agents for ABC/3TC or TDF/FTC fixed dose combinations)
• Two consecutive plasma HIV RNA viral load measurements <50 (or <400 copies/mL depending upon lowest level of detection of the local assay) in the 9 months preceding the screening visit. A single isolated HIV RNA viral load >50 (or >400) copies/mL will not exclude the patient provided the viral load result >50 (or 400) copies/mL on therapy follows a previous result <50 (or 400) copies/mL, and there is a follow-up result <50 copies/mL at least one week following the >50 (or 400) copies/mL reading in the absence of a change to any component of the ART regimen.
• CD4+ T cell count <350 cells/µL throughout the 6 months preceding the screening visit with <50 cells/µL increase in the last 12 months

Exclusion Criteria:

• Receiving a cART regimen containing an integrase inhibitor
• Anticipated change of cART in the 24 weeks following randomisation
• Participating in study with an investigational compound or device within 30 days of signing informed consent
• Use of immune modulating therapies or immunosuppressive medications within 60 days prior to study entry. Patients using inhaled or nasal steroids are not excluded
• Pregnant or breastfeeding woman
• Cow's milk allergy
• Concurrent treatment with phenobarbitol, phenytoin or rifampicin.
• A known cause of impaired CD4+ T cell gain: for example, patients with splenomegaly or individuals whose current cART regimen contains both tenofovir and didanosine