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Didanosine and amylase monitoring SIR,-Didanosine (ddl) is being increasingly used in patients symptomatic HIV infection. Adverse effects include pancreatitis reported in 3-29% of patients treated with this drug (’-5 and Bristol-Myers Squibb prescribing information). Clinicians prescribing are encouraged to maintain a high level of vigilance and to monitor serum amylase routinely. Total serum amylase is an imperfect indicator of pancreatic dysfunction. The two main sources of this enzyme are the pancreas and salivary glands. Assays specific for the pancreatic component are available although most laboratories do not use them routinely. We have assayed the pancreatic component of serum amylase in the joint British/French (MRC/ANRS) Alpha trial of didanosine in patients unable to tolerate zidovudine who have hyperamylasaemia without features of clinical pancreatitis. These assays were undertaken with the agreement of the clinicians and of the international Coordinating with

Committee. Clinicians from the UK who had patients with a raised total amylase without signs of pancreatitis were invited to send serum so that specific assays could be done. Samples from 14 patients have been assayed. Clinicians were asked if the patient had symptoms of salivary disease. Results on 1 patient with clinical pancreatitis are included for comparison (table). A second blood sample was taken at the same time and serum amylase was also measured in the local laboratory. 2 of the 15 patients with a serum amylase above the reference interval for the assay used by the local biochemistry service had a total serum amylase which would not be regarded as abnormal by the assay we used. 6 of 14 patients with symptomless hyperamylasaemia had an abnormal total amylase associated with the pancreatic component. In these patients didanosine was withdrawn because it seemed imprudent in the face of clinically silent pancreatic dysfunction to continue treatment with a drug known to damage the pancreas. The rise in pancreatic amylase in the patient with clinical pancreatitis (no 10) demonstrates that our assay reflects clinical fmdings. 3 of the 5 patients who reported dry mouths had an increase in total serum amylase which was found to be due to a disproportionate rise in the salivary component; in the other 2 the raised amylase was associated with the pancreatic component. In a patient (no 5) with parotitis the major component of the raised amylase was pancreatic. Patients 3 and 13 had a raised salivary amylase but reported no symptoms on direct questioning. The clinical findings do not always mirror the biochemical abnormality. Unlike previous reports’ our data indicate that increases in amylase without symptoms are not merely due to the salivary

component. There seems to be considerable heterogeneity in patients with symptomless hyperamylasaemia. Since clinical findings may be misleading we recommend that when a patient taking didanosine has a rise in serum amylase without symptoms, a pancreas-specific assay should be used to help with decisions about clinical management. At the recent Third European Conference on AIDS, Paris, the term "biochemical pancreatitis" was widely used. This term is both inaccurate and misleading when used to describe an increase in serum amylase of unknown origin. Pancreatitis, by definition, implies inflammation of the pancreas, and we and Yarchoan et al6 have shown that an increase in amylase activity is not synonymous with pancreatic dysfunction. If a descriptive label is required we suggest "asymptomatic hyperamylasaemia", and "subclinical

pancreatitis" once pancreatic specificity is proven. We thank Bristol-Myers Squibb for supplying didanosine for use in the MRC/ANRS Alpha trial, clinicians for providing serum samples, and the international Coordinating Committee for permission to report these findings.

serum

GLAND-SPECIFIC ASSAYS IN PATIENTS WITH RAISED TOTAL AMYLASE WHILE TAKING DIDANOSINE

i

I

MRC HIV Clinical Trials Centre, Department of Clinical Epidemiology, Royal Brompton National Heart and Lung Hospital, London SW3 6NP, UK

CHRIS VALENTINE

Department of Clinical Biochemistry, King’s College Hospital,

JEAN DEENMAMODE

London SE5

ROY SHERWOOD

1. Yarchoan R, Mitsuya H, Thomas RV, et al. In vivo activity against HIV and favourable toxicity profile of 2’,3’-dideoxyinosine Science 1989; 246: 412-14. 2. Lambert JS, Seidlin M, Reichman RC, et al. 2’,3’-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS related complex. N Engl J

Med 1990; 322: 1333-39.

3. Cooley TP, Kunches LM, Saunders CA, et al. Once daily administration of 2’,3’-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS related complex. N Engl J Med 1990, 322: 1340-44. 4. Rozencweig M, McClaren C, Beltangady M, et al. Overview of Phase I trials 2’,3’-dideoxyinosine (ddI) conducted on adult patients. Rev Infect Dis 1990; 12: S570-75. 5. Aboulker J-P, Valentine

CB, Toumene C, Darbyshire JH. An update on the Alpha trial, a study of didanosine (ddI) in symptomatic HIV positive patients intolerant to zidovudine. VIIth International Conference on AIDS (Florence, 1991); abstr

2096. 6. Yarchoan

R, Pluda JM, Thomas RV, et al. Long term toxicity/activity profile of 2’,3’-dideoxyinosine m AIDS or AIDS-related complex. Lancet 1990; 336: 526-28.

p24 antigen and HIV screening SIR,-Screening for HIV antibody in blood donations became mandatory in France in August, 1985, and the risk of transfusional contamination has been much reduced. However, the serologically silent "window" which precedes seroconversion by 6-8 weeks remains, and transmission of HIV-1 by screen-negative blood has been reported.l To tackle this residual risk, estimated at between 1 in 50 000 and 1 in 230 000,2,4 blood banks try to exclude at-risk individuals from giving blood. Another weapon could be HIV p24 antigen, which has been found during the silent window and which is the only marker of HIV infection during this period that we have.5 However, two multicentre studies in 1989 (on 1-5 million donations) failed to confirm a place for p24 screening in antibodynegative HIV-infected blood. Since then the sensitivity of p24 assay has been improved. We present a case illustrating the interest in and limits of the p24 assay for routine screening. On May 25, 1991, a 28-year-old man pricked himself on the thumb with a syringe sticking out of a garbage-bag from the office of a doctor in Paris. The accident was recorded that day at the local hospital. His blood was tested for anti-HIV-1by ELISA (Pasteur) but was negative. The man, a regular blood donor, made donations by plasmapheresis on July 2, July 30, and Sept 9, with the following results for anti-HIV serology and p24 (Pasteur): Date HIVantigen HIV p24 antigen

1

= symptomless hyperamylasaemia ’Parenthetic figures are upper limits of local laboratory reference interval tReference intervals- total < 80, pancreatic < 60, salivary < 20 IU/I P/T pancreatic -total

*In pg/ml HIV antigen (WHO reference) tFrozen sample of serum tOn plasma donation (not yet used), confirmed

by antibody neutralisation.