May 26, 2011

May 26, 2011
New Hope for People with HIV and AIDS

Welcome to another day in my life. Today is Thursday and I hope you are having a safe and great week so far. Dab the AIDS Bear and I are on the run again this week with meetings, interviews and appearances at events.

I read about some new exciting news about new anti-HIV drugs I wanted to share in my blog today. With all the bad happening to people with HIV and AIDS, it is great to be able to give some hope every once in awhile.

It has now been more than three years since a new anti-HIV medication has come on the market. However, the wait is finally over with the inevitable approval of rilpivirine in May 2011 and with many other promising drugs in Phase 2 or 3 development. Here are some highlights of exciting drugs we may see in the future.


There was some disappointing news coming from the nucleoside reverse transcriptase inhibitors (NRTIs, or nukes), the oldest class of anti-HIV drugs, with development of some drugs in this class being discontinued. This is unfortunate because the advantage of these new drugs is that they will hopefully have few side effects and have activity against HIV strains that are resistant to the older nukes.

For example, Avexa has halted the development of apricitabine because it cannot find a partner to help launch and finance the product. Apricitabine is structurally similar to Epivir and Emtriva and early studies show it may have activity against HIV strains that are resistant to older nukes including Retrovir (AZT). Side effects include nausea, diarrhea, nasal and chest congestion, and increases in triglycerides. Hopefully, another company will purchase this product and continue development.

Some good news

Racivir is an NRTI being developed by Pharmasset, Inc. and has activity against hepatitis B as well as HIV. Phase 2 trials have just been completed using a dose of 600 mg by mouth once daily. Racivir is structurally similar to Epivir and Emtriva. Continuing trials will see if it has activity against HIV strains already resistant to Epivir and Emtriva. Side effects including headache and fatigue have been reported.

Festinavir is another NRTI being developed by Bristol-Myers Squibb and Oncolys BioPharma, Inc. It is currently in Phase 2. Early studies show the once-daily oral medication has an improved safety profile when compared to older nukes, like its cousin agent Zerit.

Elvucitabine is currently in Phase 2 and is being developed by Achillion Pharmaceuticals. Studied doses are 5 or 10 mg by mouth once daily. This drug shows activity against hepatitis B as well as HIV and may have activity against HIV strains that are resistant to other NRTIs, including Epivir and Retrovir. This drug has a very long half-life, making it more forgiving if a dose is forgotten.


In addition to the promising rilpivirine, other second-generation non-nucleoside reverse transcriptase inhibitors are currently being developed.

RDEA806 by Ardea has completed Phase 2 trials. It has been shown to be active against HIV strains resistant to Sustiva. Secondary data have shown it can reduce uric acid levels. Another NNRTI in Phase 2 is GSK2248761 (formally IDX899). It is being developed by ViiV Healthcare. This drug is less susceptible to resistance when compared to the older NNRTIs on the market (Sustiva and Viramune). ViiV has another NNRTI called lersivirine that is also less susceptible to resistance when compared to older NNRTIs on the market. A Phase 2 trial is currently underway comparing it to Sustiva.

Integrase inhibitor and new booster

The integrase inhibitor class of medications has many exciting drugs in development. Elvitegravir is an integrase inhibitor (same class as Isentress) being developed by Gilead, now in Phase 3. It does not require dose adjustments for individuals with kidney problems. This drug needs to be boosted for it to be effective.

One of the most exciting drugs in development is a new booster drug called cobicistat (GS-9350), also being developed by Gilead. It may be the first alternative to taking low-dose Norvir to increase concentrations of other drugs, including elvitegravir. It should be noted that it has no activity against HIV. Cobicistat has just started two Phase 3 studies comparing a once daily, fixed dose Quad regimen (four in one combination of GS9350, elvitegravir, and Truvada) vs. once daily, fixed dose Atripla and Norvir-boosted Reyataz and Truvada. This stems from the good results of the Phase 2 head to head study presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in 2010. The Quad was non-inferior to Atripla in safety and efficacy. Gilead is also going to start a Phase 3 study with cobicistat as a stand alone booster. The study will evaluate efficacy, safety, and tolerability of cobicistat-boosted Reyataz vs. Norvir boosted Reyataz, each with a Tru vada backbone.

Shionogi-ViiV Healthcare has started Phase 3 trials for a once-daily, unboosted integrase inhibitor called S/GSK1349572 (572 for short); and a co-formulation of 572 with Epzicom (known as 572-Trii), also in Phase 3. Phase 2 studies of 572 demonstrated potent anti-viral activity with good tolerability, and activity against strains already resistant to Isentress. Both elvitegravir and 572 offer an advantage over Isentress, being dosed once daily instead of twice daily. Both are expected to have limited cross resistance with Isentress as well, but more data from studies are needed.

CCR5/CCR2 antagonist

Tobira Therapeutics is developing a new dual CCR5/CCR2 antagonist called TBR-652 that not only shows potent anti-viral activity but has a potential anti-inflammatory benefit as well. Inflammation in HIV positive individuals can increase risk of heart disease, dementia, and other age related problems. Unlike Selzentry, TBR-652 is dosed once daily, giving it an advantage when compared with other anti-virals. It is continuing Phase 2 studies.

It is exciting to see what the future of HIV therapy might bring. But remember, highly active drugs are already available. Make sure to be adherent on your current regimen to avoid resistance and live a long, healthy life.

Until we meet again; here's wishing you health, hope, happiness and just enough.

big bear hug,

Daddy Dab