Rilpivirine + darunavir HIV maintenance regimen matches standard three-drug antiretroviral therapy

An 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 three-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 three-drug antiretroviral therapy (ART) – which typically contains two 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 an appropriate option for some people who experience NRTI-related side effects or toxicities.

Franco Maggiolo from Azienda Ospedaliera Papa Giovanni XXIII 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 viral 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 six years and had used a median of three regimens. People with known rilpivirine resistance and those with hepatitis B virus co-infection 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 Kivexa or Epzicom) for at least six months. Most were taking tenofovir/emtricitabine and the most commonly used protease inhibitors were boosted atazanavir (Reyataz) and boosted darunavir. They were randomly assigned to either remain on their current regimen or switch to rilpivirine plus boosted darunavir.

At 24 weeks – the primary endpoint – 100% of participants who switched to rilpivirine plus boosted darunavir maintained an 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 three-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 three-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 (indicated by estimated GFR) 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 summarised. "[Rilpivirine + boosted darunavir] presented slight immunologic advantages and was well-tolerated with a favourable renal and bone safety profile."

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