August 14, 2006

IAC: Serostim As Immune-Based Therapy?

Recombinant human growth hormone (Serostim®), best known as an approved anti-wasting treatment and an experimental anti-lipodystrophy agent, has entered an unexpected area of HIV treatment research: immune-based therapies. New data, reported today at the XVI International AIDS Conference (IAC) in Toronto, suggest Serostim may have a lot to offer in this regard.

An important goal of immune-based therapy research is the development of treatment strategies that can increase CD4 cell counts (T cell counts). However, it's not just about the quantity of CD4 cells, its also about their quality.

New, or "naive," CD4 cells – cells produced by the bone marrow and then matured in the thymus gland – are crucial to a functioning immune system, yet they are often wiped out by HIV early on in the course of infection. In turn, researchers have strived to find ways to therapeutically increase these cells.

This, however, is easier said than done. In late childhood, after the immune system has produced all of the naive CD4 cells it thinks the body needs for life – not anticipating an immune-damaging infection like HIV – the function of the thymus slows considerably. The small gland, located immediately above the heart, becomes filled with fat and stops producing new CD4 cells.

Enter Serostim, a drug known for its fat-busting potential in clinical trials involving HIV-positive people with lipodystrophy. Researchers have suggested that it might be possible to use Serostim to flush fat out of the thymus and, if all goes well, jumpstart the gland's ability to churn out new CD4 cells.

After the successful completion of a few small pilot studies, the federally funded AIDS Clinical Trials Group conducted a larger study (A5174) involving 60 HIV-positive people to further explore the possible immunologic benefits of Serostim treatment. The volunteers had been on HIV treatment for at least a year with undetectable viral loads for at least six months, but were struggling to get their CD4 cell counts above 350.

One group of patients (Group A) received 1.5mg daily injections of Serostim plus a standard HIV drug regimen for 48 weeks. A second group of patients (Group B) took standard HIV drug treatment alone for 24 weeks and then added 3.0mg daily injections of Serostim for the remaining 24 weeks of the study.

Twenty of the 60 patients agreed to undergo CAT scanning upon entering the study and after 24 weeks of Serostim treatment to measure changes in their thymus glands.

The study results, reported by Dr. Kimberly Smith of Rush University Medical Center in Chicago, indicate that study volunteers in both groups had an increase in their CD4 cell counts after 48 weeks. The researchers also noted an increase in thymus size – an encouraging sign of thymus activity– in seven of 11 participants in Group A and seven out of nine patients in Group B. Finally, the number and percentage of naive CD4 cells increased in association with Serostim therapy.

While there is still more to be learned about the benefits and safety of Serostim as an immune stimulant, Dr. Smith and her colleagues suggest these data are definitely a step in the right direction and should be followed up with more extensive testing in clinical trials.


Source:
Smith K, Zheng L, Bosch R, et al. Treatment with recombinant human growth hormone (r-hGH) leads to increased thymic output in HIV-infected subjects with incomplete immune reconstitution on highly active antiretroviral therapy (HAART) [Abstract MOAX0403]. XVI International AIDS Conference, Toronto, 2006.

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