False positives and negatives in routine testing for drugs of abuse

compared with the same age group in the Ivorian population. The average crude mortality rate among displaced Liberians exceeded the usual severity threshold set at 1 per 10000 per day.2 Appropriate food supply, vulnerable

nutritional support, and reinforcement of the health facilities are urgently needed. The plight of displaced Liberians fleeing the chronic insecurity in their country, though it is no longer in the limelight, should still be regarded as an acute public health concern by the host countries and international

agencies.

GC-MS would not be affected by sample adulteration, nor would it give false positives or false negatives, possibly allowing a less rigorous collection procedure that might be more acceptable to prisoners. Financial savings would be made by removing the initial screen. *Lidia J Notarianni, Diane Belk, A J Collins School of

Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK

Treatment of children with HIV infection

*Francis Varaine, Marie-Josée Michelet *Epicentre, 8 rue Saint-Sabin, 75011 Paris, France;

and Médecins Sans

Frontières,

Paris

1 Enquête nutntionnelle auprès d’une population de réfugiés libériens. Préfecture de Tabou. Côte d’Ivoire, 1994. Paris: Action Internationale Contre la Faim, 1994. 2 Famine-Affected, refugee, and displaced populations: recommendations for public health issues. MMWR 1992; 41: RR-13.

False positives and negatives in routine testing for drugs of abuse testing of prisoners for drugs of abuse began in seven prisons in England and Wales in February, 1995, with the aim of rapid expansion to all prisons in the UK. Because of the large number of samples that this programme will generate, about 10% of the prison population will be tested per month, and both speed and cost are important factors in choice of the method of analysis. Urine only is tested at present, with methods based on competition for an antibody-binding site between the drug in urine and (added) labelled drug. Such assays allow rapid qualitative and quantitative analysis, although positive results always need SIR-Random

confirmation by gas

chromatography-mass spectrometry (GC-MS), since this is the only method that can separate a drug from other components and allow unambiguous identification. These preliminary screening tests rely on an interaction between a protein (antibody) and drug molecules. Proteins

readily be denatured, resulting in a loss in binding capacity for the drug and yielding false results. Hence there are strict protocols in place for the collection and handling of specimens to eliminate the potential for adulteration, procedures that prisoners might find demeaning. We have investigated the robustness of these initial screening tests to see whether the results are affected by sample contamination can

by common substances. We have taken urine containing various drugs of abuse and drug-free urine, and added bleach, soap, and dilute acid in amounts that did not affect the pH or colour of the sample. With the Syva assay (kits being used for the compulsory testing of urine samples in prison) these added substances caused the assay to produce false negatives because of interference with the antibody-drug interaction. Other available test kits with the same principle yielded false negatives and false positives. The reported results from the first weeks of random urine testing of the prison population in England and Wales have shown that between 50% and 80% of generated samples have proved positive. All these positive samples need confirmation by GC-MS and we understand that this is being done. In view of our findings, a random sample of the negative specimens should also be tested by GC-MS to confirm that they are true negatives. The high proportion of positive results requires that most samples are retested with GC-MS. This retesting, combined with the potential for false negatives, suggests that the procedure could be simplified by use of only GC-MS.

SIR-Rowe, in his news item (Feb 25, p 511), refers to the release of interim results of a large clinical trial in the USA (AIDS Clinical Trials Group [ACTG] 152) in symptomatic HIV-infected children who were randomised to receive either didanosine or high-dose zidovudine, or didanosine plus zidovudine at a lower dose. The data and safety monitoring board (DSMB) recommended that the high-dose zidovudine arm be stopped because of both lower efficacy in terms of progression of HIV infection (defined

growth failure, neurodevelopmental deterioration, opportunistic infections, or death) and greater toxicity than the best of the other two regimens. However, the didanosine and the zidovudine plus didanosine arms will remain blinded until August, 1995, as originally planned; at present any differences between them are clearly not great enough for the DSMB to recommend unblinding. In the mean time, the present policy of zidovudine as first-line antiretroviral therapy for HIV-infected children will continue in the USA and indeed children in the zidovudine monotherapy group as

will be allowed to remain

on

zidovudine

or

switch

to

other

1

therapies.’

Aside from concerns about the clinical importance of the growth and neurodevelopmental endpoints, the details of which have not been released, there are several other issues to consider with respect to didanosine. First, this drug crosses the blood-brain barrier poorly2 and until further information is available there should be concerns about this drug being used as monotherapy, especially in children with HIV encephalopathy. Second, a special formulation of didanosine was made up for the ACTG 152 trial but is not widely available. The paediatric formulation of didanosine that is available in Europe is very unpalatable and many paediatricians have reported that children are often resistant to taking it. The interim results of the ACTG 152 trial are the first to suggest that zidovudine monotherapy might be of lower efficacy than another anti-HIV therapy (either didanosine or even both regimens) in patients not previously treated with zidovudine. Three large trials in adult (two in the USA, one in Europe) comparing combinations of zidovudine and didanosine with zidovudine alone and, in one of them, with didanosine monotherapy as well, are continuing with results expected in late 1995, early 1996. Until data from these trials as well as further data from ACTG 152 become available, it would be difficult and unwise to alter the present policy of prescribing zidovudine as first-line therapy in children with HIV infection. *D M Gibb, J H Darbyshire, M Debré, C Giaquinto, J P Aboulker, M Martinez, G Tudor-Williams, for PENTA (Paediatric European Network for Treatment of AIDS) Epidemiology and Biostatistics, Institute of Child Health, London WC1N 1EH, UK

1

2

Questions and answers about ACTG protocol 152. Bethesda: National Institute of Allergy and Infectious Diseases, National Institutes of Health, 1995. Balis FM, Pizzo PA, Butler KM, et al. Clinical pharmacology of 2’,3’-dideoxyinosine in human immunodeficiency virus infected children. J Infect Dis 1992; 165: 99-104. 1115