TreatmentUpdate77 - Vol. 7, No. 7; April 1997
Sean Hosein

PWAs can develop bone marrow damage because of infection by HIV and other microbes, cancer and the toxicity of certain drugs. This damage can reduce the production of certain white blood cells called neutrophils. When the level of neutrophils falls below normal (a condition known as neutropenia), people become at risk for developing serious bacterial and fungal infections. To boost levels of neutrophils doctors can cause the bone marrow stimulant G-CSF (granulocyte-colony stimulating factor) also called Filgrastim.

Study details

Doctors in Western Europe enrolled 200 subjects (23% female, 77% male) most of who had very low CD4+ cell counts, indeed, 50% had 10 CD4+ cells. Nearly 80% of subjects had AIDS and none had received anticancer drugs nor radiation. All subjects had neutropenia.

Subjects received G-CSF every day until their neutrophil counts rose to acceptable levels. The starting dose was 1 g/kg of body weight per day and this was increased every three days if necessary. After the first 4 weeks of the study, subjects could continue to receive at least 300 g/week of G-CSF to maintain their neutrophil count. The drug was injected under the skin either by nurses or the subjects.

Results -- Recovery

Sixty-percent of subjects recovered from neutropenia after just 2 days of G-CSF use and 98% recovered within the first 4 weeks of the study. As little as 1 g/kg/day of G-CSF was able to raise neutrophil levels significantly in 50% of subjects. Once recovered, 72% of the subjects used about 2-3 doses/week of G-CSF to maintain their neutrophil count.

CD4+ and CD8+ counts

In a subgroup of 97 subjects, G-CSF caused about a 30% increase in the CD4+ and CD8+ cell counts. Readers should remember that these counts were very low at the start of the study and the doctors didn't think that the increased cell counts helped improve the condition of subjects.

Toxicity

About 12% of subjects reported muscle and bone pain as a result of G-CSF injections. Although 16 subjects died during the study, none of the deaths were due to G-CSF. The drug did not appear to increase production of HIV as measured by p24 antigen tests.

Causes of low neutrophil levels

The doctors considered the following drugs to be responsible for bone marrow damage in many of the subjects:

* AZT

* Bactrim/Septra«

* ganciclovir

* pyrimethamine

The value of G-CSF is that it allowed a least 80% of subjects who used these drugs to continue taking them without suffering from bone marrow toxicity.

REFERENCES:

1. Hermas P, Rozenbaum W, Jou A, et al. Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection. AIDS 1996;10(14):1627-1632.

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