Neutropenia occurs when the level of neutrophils, a type of white blood cell, falls below normal. The usual range is between 2.5 and 7.5 x 10⁹ per litre.

Neutrophils are required in order to control bacterial and fungal infections, and are produced from stem cells in the bone marrow. However, a number of factors can adversely affect the production of stem cells, including cancer chemotherapy, anti-retroviral drugs such as AZT, the CMV treatment ganciclovir, and the antibiotic co-trimoxazole. Neutropenia has been observed to occur in up to 30% of patients within three months of starting treatment at higher doses of AZT, but occurs much less frequently since the introduction of 500 mg a day dosing. The risk of developing neutropenia whilst on AZT does not appear to increase with time; the risk is considerably greater during the first three months.

Neutropenia can also occur in advanced HIV infection in the absence of treatment with myelosuppressive drugs (drugs which affect the production of stem cells in the bone marrow). The incidence may be as high as 20-30% if the placebo arms of clinical trials in advanced HIV disease are an accurate reflection of incidence. Highly active antiretroviral therapy has been shown to improve neutrophil function and reduce neutropenia.

Moderate to severe neutropenia may increase the chances of bacterial infection, especially in people with advanced immunosuppression. Symptoms of neutropenia are indirect ones, and the chief contribution of neutropenia to ill-health is that it permits the development of other infections. It can only be detected by a neutrophil count.

The risk of developing bacterial infections increases substantially in people with HIV when the neutrophil count falls below 1 x 10⁹, and the relative risk increases eight-fold when the neutrophil count falls below 0.5 x 10⁹. However, it should be noted that the incidence of serious bacterial infections in those with a neutrophil count below 0.5 was three to five infections per 100 patient months of neutropenia (in a cohort of 118 neutropenic patients).

In patients with AIDS and neutropenia, G-CSF has been shown to reverse neutropenia in 96% of patients after 28 days of treatment; 60% achieved reversal of neutropenia within two days. G-CSF has been shown to maintain neutrophils within the normal range for at least 11 months on treatment, and to reduce rates of bacterial infections and hospitalisation. See Colony stimulating factors in Drugs used by people with HIV: Immune-modulating drugs for further details.

G-CSF treatment may be particularly valuable in patients receiving ganciclovir for CMV disease, since it will allow concurrent therapy with AZT if the neutropenia can be reduced. However, other drugs for managing CMV retinitis are available, such as foscarnet, which do not encourage the development of neutropenia, and these may prove to be better tolerated and more economic to use.

References

Garavelli PL. Efficacy of recombinant granulocyte colony-stimulating factor in the long-term treatment of AIDS-related neutropenia. AIDS 7(4): 589-590, 1993.

Hermans P et al. Clinical use of haematological growth factors in patients with human immunodeficiency virus (HIV-1) infection. Biomedical Pharmacotherapy 48(2): 69-72, 1994.

Moore RD et al. Neutropenia and bacterial infection in acquired immunodeficiency syndrome. Archives of Internal Medicine 155(18): 1965-1970, 1995.