by Chael Needle

LifeGuide [Treatment Horizons]

With the flu vaccine shortage in full swing, perhaps it’s time to turn our attention to another type of pneumonia important for people living with HIV/AIDS to pay attention to: PCP, a severe illness that is the most common infection for people with AIDS and is often fatal if left untreated. Most seriously affecting those who are immunosuppressed, PCP is caused by a fungus (though some classify it as a parasite) once called Pneumocystis carinii but now called Pneumocystis jiroveci. Though the flu vaccine won’t protect you from getting PCP, PCP can be treated. You should also consult with your doctor about prevention before the initial symptoms—dry cough, fever, difficulty with breathing—arrive.

Some people with HIV are more at risk of developing PCP than others. Those who have T-cell counts below 200; have oral thrush or unexplained fevers lasting more than two weeks, whether or not their T-cell counts fall below 200; and those who have had PCP before, no matter their current T-cell count, should take medications to prevent infection. Women who are HIV-positive might be wary of PCP as their T-cell counts often fall during their third trimester. Research also shows that smokers develop PCP more rapidly than non-smokers.

PCP has been a waning problem in the era of combination antiretroviral therapy, which acts as a preventative as T-cell counts are kept up. Early in the epidemic, an estimated seventy-five percent of HIV-positive individuals developed PCP at some point during their lifetime, but since the advent of prophylactic medications rates range from ten to twenty percent. The treatment widely thought to be the best prevention is trimethoprim-sulfamethoxazole, or TMP-SMX, a combination of two medicines. The drug, which is also used to treat PCP, has many different brand names (Bactrim and Septra are two). Other drugs used in treatment and/or prevention are dapsone, pentamidine, and atovaquone. Discontinuation of prophylactic treatments is possible if T-cell counts are high enough and viral loads low enough for a sustained period of time. Since 1990, the use of corticosteroids as adjunctive therapy in the treatment of moderate to severe PCP to reduce inflammation of the lungs has been the standard of care.

A potential new treatment for PCP is making its way through the pipeline. Immtech International, Inc., which focuses on the research and development of novel oral therapeutics, specifically those involving infectious disease, is currently testing DB289 for the treatment of malaria, trypanosominasis (more commonly known as African sleeping sickness), and PCP.

Early clinical trials showed that more than ninety percent of patients exhibited improved lung function following treatment with DB289. Within three days, some patients showed improved function; after twenty-one days, most had substantially improved. DB289, an oral formulation, is the only compound in development, at present, for this particular disease. DB289 as a treatment for PCP is currently in Phase IIb development.

The Peru-based Phase II trial enrolled AIDS patients who failed standard therapy for PCP. A pilot group of patients  was treated with 50 mg of DB289 twice daily for twenty-one days; results showed this dose was well-tolerated and efficacious. Subsequent patients in the trial are receiving a higher dosage of 100 mg twice per day to determine if the time to cure PCP or improve lung function can be reduced. Early results have confirmed the enhanced efficacy of the 100 mg dose regimen of DB289 against PCP in all patients treated so far. In addition, the length of time for the return of patients’ normal lung function after start of treatment with the 100 mg dose has been reduced by approximately one week compared to pilot study results. No significant adverse side effects were reported.

While Immtech has received FDA fast-track approval for the development of DB289 as a treatment for African sleeping sickness, its progress to Phase III trials for AIDS-related PCP is now a matter of watch-and-wait.

Chael Needle wrote about neurological problems possibly associated with HIV/HCV coinfection in the October issue.