RESEARCH & DEVELOPMENT

High-dose aldesleukin raises CD4+ cell count in HIV infection

High-dose aldesleukin* in combination with antiretroviral treatment markedly increases CD4+ cell counts and is tolerable in patients with early mv infection, report US-based researchers.

In this study, 49 such patients aged ~ 18 years with a CD4+ cell count of ~ 500/mm3 who were already receiving antiretroviral therapy were randomised to receive SC aldesleukin ['Proleukin'] 1.5MU (low­dose) twice daily on days 1-5 every 4 (n = 12) or 8 weeks (13), or aldesleukin 7.5MU (high-dose) twice daily on days 1-5 every 4 (11) or 8 weeks (13), for ~ 4 months. **t

Dose-dependent increases During treatment, dose-dependent increases from

baseline were observed in both CD4+ cell and CD4+ cell percent slopes. In high-dose recipients, mean CD4+ cell and percent slopes were +116.1 cells and +2.7% per month, respectively; corresponding figures for low-dose recipients were +26.7 and +1.3%, respectively.

After 6 months, increases from baseline in mean CD4+ cells and percent were 94.8 and 44.3%, respectively, for high-dose recipients; corresponding figures for low-dose recipients were 19 and 19%, respectively.

In all treatment groups, a decline in viral load was observed.

Adverse events At 6 months, 29/49 patients (59%) had experienced

~ 1 grade 3 toxicity; the most commonly experienced adverse events were fatigue and malaise (32%), myalgias (21 %), arthralgias (12%) or sleep dis­turbances (11 %). No grade 4 toxicities were observed.

After a further 12 months' follow-up, the 39 remaining aldesleukin recipients had a mean CD4+ cell count of 1381/mm3 and a CD4+ cell percent of 48%. Patients received 5-day cycles of aldesleukin at a mean interval of 12 months.

The researchers comment that 'it appears that the rigors of a more intensive regimen early on are rewarded by the need for less frequent cycling subsequently' .

• Chiron; phase m in HIV infection

•• 7idovudine was the mostfrequently used anJiretroviraJ agent.

tAt 6 months, a11 patients were offeredfiuther aldesleukin therapy. Ifnecessary, dosage and/or frequency of adminisJratWn were increased. to optimise response.

Davey Ir lIT, awtt DO, Albert 1M, Piscitelli sc, Kovacs IA. A randomized trial of high venus low-dose subcutaneous interJeukin-2 outpatient therapy foc early human immnnodeficiency virus type 1 infection. Iournal of Infectious Diseasea 179: 849-858, Apr 1999 ~

> Editorial comment: An N formulation of aldesleukin has been launched in the US, Europe, South Korea and Canada for the treatment of metastatic renal cell carcinoma, and is registered in Canada and the US for the treatment of metastatic melanoma.

1173-832419911184-00091$01.000 Adl. International Llmltecl1m. All rlghta reaerved

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Inpharma-24 Apr 1m No. 1114