1st International Workshop on HIV Drug Resistance & Treatment Strategies 25-28 June 1997, St. Petersburg, Florida, USA

A PHASE I/II STUDY OF BB-10010, AN ANALOGUE OF HUMAN MIP1-α, IN ASYMPTOMATIC HIV-INFECTED PATIENTS WITH CD4+ CELL COUNTS LESS THAN 500 cells/ml

Antiviral Therapy 1997;2 (Suppl 5):2 (abstract no. 4)

IG Williams¹, JA McKeating², J Lewis³, KM Dawson³, LG Czaplewski³, R Puttick³, P Balfe¹ and IVD Weller^1
1Departments of Virology and Sexually Transmitted Diseases, University College London; ²School of Animal and Microbial Sciences, University of Reading; and ³British Biotech Pharmaceuticals, Oxford, UK.

BACKGROUND: A possible therapeutic strategy for treatment of HIV infection is the development of CC chemokine analogues which inhibit HIV entry into cells via chemokine receptors. BB-10010 is a recombinant variant of human MIP1-α which has been shown to inhibit HIV infection in vitro.

OBJECTIVES: To determine the tolerability and antiviral effect of BB-10010 in patients with asymptomatic HIV infection and the co-receptor repertoire of viruses isolated from these individuals.

METHODS: Eleven antiretroviral-naïve, asymptomatic patients were treated with BB-10010, 300 mg/kg subcutaneous once daily for 7 days. Patients underwent clinical assessments, laboratory tests for safety, and measurement of plasma HIV RNA levels, CD4+ cell counts, and BB-10010 plasma levels. Viruses were isolated from PBMC samples taken prior, during (day 7) and post-therapy (day 35) and were tested for their ability to infect U87/CD4 cells stably expressing a number of chemokine receptors (CCR-1, -2b, -3, -4, -5 and CXCR4).

RESULTS: BB-10010 was well tolerated with no serious clinical or laboratory adverse events observed. Overall there was no change pre- and post-treatment in plasma HIV RNA levels or CD4+ count. One patient withdrew from the study on day 14 to start antiretroviral combination therapy.

Virus isolates were obtained from nine patients. Isolates from two patients were able to replicate in MT-2 cells which correlated with CXCR4 usage in U87/CD4 cells. All virus isolates showed similar patterns of co-receptor usage over the course of treatment. The median plasma levels of BB-10010 was 3.5 ng/ml (range 0.7-5.4).

CONCLUSIONS: There was no change in CD4+ count and plasma HIV RNA levels during treatment with BB-10010. Plasma levels of BB-10010 were low and may account for this lack of antiviral effect. There may also be variation in viral sensitivity to neutralization by BB-10010. In vitro sensitivities of the patients virus isolates to BB-10010 will be presented.

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1997-06-25
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