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IAS 2015: Rilpivirine + Darunavir HIV Maintenance Regimen Matches Standard 3-Drug ART

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A NRTI-sparing dual antiretroviral regimen consisting of the NNRTI rilpivirine (Edurant) plus the boosted HIV protease inhibitor darunavir (Prezista) maintained viral suppression and was well-tolerated by people who switched from a standard 3-drug regimen, according to results from the PROBE study presented at the recent 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Vancouver.

Standard 3-drug antiretroviral therapy (ART) -- which typically contains 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either a NNRTI, protease inhibitor, or integrase inhibitor -- is safe and effective for most people with HIV. But a NRTI-sparing regimen may be appropriate for some people who experience NRTI-related side effects or toxicities.

Franco Maggiolo from Azienda Ospedaliera Papa GiovanniXXIII in Bergamo, Italy, and colleagues conducted a prospective pilot study in which treatment-experienced people with undetectable viral load switched from a standard regimen to rilpivirine plus ritonavir-boosted darunavir.

This open-label trial included 60 participants with stable virological suppression. Most (80%) were men and the average age was 48 years. The mean baseline CD4 T-cell count was high, at over 600 cells/mm3, but about 20% had a previous AIDS diagnosis. They had been on antiretrovirals for a median of about 6 years and had used a median of 3 regimens. People with known rilpivirine resistance and those with hepatitis B virus coinfection were excluded.

At baseline participants were taking a boosted protease inhibitor with either tenofovir/emtricitabine (the drugs in Truvada) or abacavir/lamivudine (the drugs in Epzicom or Kivexa) for at least 6 months. Most were taking tenofovir/emtricitabine and the most commonly used protease inhibitors were boosted atazanavir (Prezista; 57%) and boosted darunavir (43%). They were randomly assigned to either remain on their current regimen or switch to rilpivirine plus boosted darunavir.

Results

  • At 24 weeks -- the primary endpoint -- 100% of participants who switched to rilpivirine plus boosted darunavir maintained undetectable viral load (<50 copies/mL), compared to 87% of those who stayed on their baseline regimen.
  • The difference of 13% indicated that rilpivirine plus darunavir was non-inferior to standard 3-drug ART.
  • By 48 weeks, the response rate was slightly lower in the rilpivirine plus darunavir arm and higher in the standard therapy arm, so the difference was smaller.
  • Participants taking rilpivirine plus darunavir had larger CD4 cell gains than those remaining on a 3-drug regimen at week 24 (mean +24 vs +13 cells/mm3), but this reversed by week 48.
  • People on rilpivirine plus darunavir saw a greater decrease in activated (+CD38+HLA-DR) CD8 T-cells at 24 weeks, but the decline continued in both arms and levels were similar by week 48.
  • Both the NRTI-sparing and the baseline regimens were generally safe and well-tolerated, with no adverse events leading to drug discontinuation.
  • At week 24 participants who switched to rilpivirine plus darunavir had a smaller increase in fasting triglycerides, but larger rises in both total and HDL "good" cholesterol -- patterns that persisted at week 48.
  • Bone mineral density remained the same in both arms at week 48, though bone T-scores and Z-scores fell more in the standard therapy arm.
  • Kidney function (as indicated by eGFR) remained stable in both treatment arms.

"In well-controlled HIV-positive patients switching combination ART, [rilpivirine + boosted darunavir] was virologically effective and resulted in no virologic failure over 48 weeks of follow-up," the researchers summarized. "[Rilpivirine + boosted darunavir] presented slight immunologic advantages and was well-tolerated with a favorable renal and bone safety profile."

"Switching to this dual, NRTI-free regimen may be an option for patients experiencing NRTI-related toxicity," they concluded.

9/8/15

Reference

F Maggiolo, D Valenti, A Callegaro, et al. Switch from PI/RTV +2 nucleos(t)ides to RPV+DRV/RTV maintains HIV suppression and is well tolerated (PROBE study). 8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Vancouver, July 19-22, 2015. Abstract TUPEB270.