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.

Glossary

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

pilot study

Small-scale, preliminary study, conducted to evaluate feasibility, time, cost, adverse events, and improve upon the design of a future full-scale research project.

 

CD8

A molecule on the surface of some white blood cells. Some of these cells can kill other cells that are infected with foreign organisms.

non-inferiority trial

A clinical trial which aims to demonstrate that a new treatment is not worse than another. While the two drugs may have comparable results in terms of virological response, the new drug may have fewer side-effects, be cheaper or have other advantages. 

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.

References

Maggiolo F 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 (IAS 2015), Vancouver, abstract TUPEB270, 2015.