Second International Congress Drug Therapy in HIV Infection 18-22 November 1994 Glasgow, UK

QUANTIFICATION OF SERUM VIRAL LOAD, RESISTANT MUTATIONS AND CLINICAL OUTCOME IN PATIENTS (MRC ALPHA TRIAL) STOPPING ZIDOVUDlNE (ZDV) AND COMMENCING DIDANOSINE (ddl)

C Loveday, L Comber, U Ayliffe, JH Darbyshire*., A Babiker*, RS Tedder, A Valentine, A Pinching and The Alpha Coordinating Committee.
Division of Virology, University College London Medical School,MRC HIV Clinical Trials Centre*, London, UK.

Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.6
AIDS 1994, Vol. 8 (Suppl. 4);S5

The objectives of this study were to quantify both serum HIV-I viral load from the start of ddl therapy, and the changes in resistant genomic mutations associated with prior ZDV and subsequent ddl therapy. Twenty seven patients (16 high dose-HD), 11 low dose-LD) in the UK archive were available for the study; 13 patients with more than 3 blood samples after start of ddl (8HD, 5LD) had serum HIV-I RNA quantified by an immunocapture PCR, (RNA copiesJrnl), and genomic resistance measure at codons 41, 215 and 74 by a point mutation assay (PMA).

The mean duration of prior ZDV therapy was 380 days (range 13-982 days) followed by a mean dmg rest of 155 days (range 50-515 days); ZDV resistance prior to ddl therapy at codon 41=53% (range 7-95%), codon 215=78% (range 6-100%) and codon 74=<2%.

The mean pre-ddl viral load in 13 patients followed longitudinally was 3970c/ml (range 520-7000c/ml) in the 8HD patients and significantly higher at 7340c/ml (range 5700-10500c/ml) in the 5LD patients (p<0.05). This difference disappeared at 50 days as viral load fell, and after a mean follow-up of 218 days (85-375 days) there was a significant drop in viral load in both HD patients (986c/ml) and LD patients (1700c/ml) (p<0.01).

Resistance at codon 74 measured up to 200 days revealed a mean rise from <2% to 74% in HD patients, and a significantly lower rise from <2% to 28% in LD patients (p<0.05 at 150 and 200 day intervals).

In 8 of 9 patients with rising genomic resistance at codon 74 there was an associated falling or persistently low semm viral load. In the same 9 patients pretreatment genomic resistance >95% at codon 215 remained unchanged and genomic resistance <85% began to fall as resistance at codon 74 rose. In 3 patients resistance at codon 41 evolved from <2% to 78% (range 64-85%) during ddl therapy.

Serum viral load showed a mean fall of 0.77 log₁₀ over the study period as resistance at codon 74 increased from <2% to 45%. The acquisition of resistance at codon 74 was dose dependent. A reciprocal relationship between codon 215 and 74 was only seen if pretreatment 215 prevalence was submaximal.

Presenting author: C Loveday

1994-11-18
5.6

Originally published in AIDS Volume 8, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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