Study of Darunavir/r + Tenofovir/Emtricitabine vs. Darunavir/r + Raltegravir in HIV-infected Antiretroviral naïve Subjects (ANRS 143)

The triple therapy darunavir/r + tenofovir/emtricitabine is likely to become a relevant first-line treatment option in the years to come. The dual combination of boosted darunavir + raltegravir is an innovative treatment option that combines two potent new antiretroviral drugs, one of which belongs to a new drug class (integrase inhibitor). The expected efficacy profile of this combination is promising. Moreover, this combination might have a better tolerance profile and has the advantage of sparing the NRTI class.

In the context of tenofovir/emtricitabine currently being a reference backbone in first-line antiretroviral regimens, we hypothesise that, in combination with darunavir/r, raltegravir may be an alternative option if its efficacy is non-inferior to tenofovir/emtricitabine.

• Drug: darunavir/ritonavir QD + raltegravir BID

  darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD)

  ritonavir 100 mg, 1 tablet once daily (QD)

  raltegravir 400 mg, 1 tablet twice daily (BID)

• Drug: darunavir/r QD + tenofovir/emtricitabine QD (fixed dose combination)

  darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD)

  ritonavir 100 mg, 1 tablet once daily (QD)

  tenofovir/emtricitabine 245/200 mg, fixed dose combination, 1 tablet once daily (QD)

• Active Comparator: darunavir/r + tenofovir/emtricitabine
  Intervention: Drug: darunavir/r QD + tenofovir/emtricitabine QD (fixed dose combination)
• Experimental: darunavir/r + raltegravir
  Intervention: Drug: darunavir/ritonavir QD + raltegravir BID

Inclusion Criteria:

• Patient with confirmed HIV infection
• Age ≥ 18 years
• Written informed consent
• Male patient or non-pregnant, non-lactating female
• No previous treatment with any antiretroviral drugs
• HIV-1 RNA > 1000 copies/ml
• Indication to start an antiretroviral treatment as long as subject has also a CD4 cell count ≤ 500/mm3 either at screening or on a sample taken within 3 months before screening
• No major IAS-USA mutations on genotypic testing at the screening visit or on any historical genotype, if available

Non-inclusion Criteria:

• Woman without effective contraception method (recommended contraception during the trial is mechanical + a second method other than an oral contraceptive)
• Pregnant or breastfeeding woman
• Woman expecting to conceive during the study
• HIV-2 co-infection
• Creatinine clearance < 60 ml/mn (Cockcroft & Gault equation), alkaline phosphatase, ASAT, or ALAT ≥ 5 ULN
• Patient with significant impairment of hepatic function, defined as serum albumin < 2.8 g/dl or INR > 1.7 or presence of ascites, in the absence of another explanation for the abnormal finding
• CD4 > 500/mm3 at screening, except in case of symptomatic HIV disease (defined by conditions qualifying for CDC category B or C) or CD4 ≤ 500/mm3 on a sample taken within 3 months before screening.
• Any major IAS-USA mutation conferring resistance to one or more of reverse transcriptase or protease inhibitors on genotypic testing at screening
• Mycobacteriosis under treatment
• Malignancy requiring chemotherapy or radiotherapy
• Positive HBs Ag
• HCV infection for which specific treatment is ongoing or planned during the first year on trial treatment
• Known hypersensitivity to one of the trial drugs or its excipients
• Contraindicated concomitant treatment
• Anticipated non-compliance with the protocol
• Participation in another clinical trial with an on-going exclusion period at screening
• Subject under legal guardianship or incapacitation
• Subject, who in the opinion of the investigator, is unable to complete the study period