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Doubts about zidovudineDebate about the efficacy and safety of zidovudine (AZT) is

being stifled by a medical and scientific community that continuesto display a striking arrogance over those it claims to serve, says aUK television documentary (Dispatches, Channel 4) screened thisweek. These criticisms have been the subject of intense discussion inthe USA, where several AIDS organisations are now campaigningagainst the more widespread prescription of zidovudine to

symptom-free HIV-positive individuals. Help groups have evenbeen established to enable HIV-positive patients gain theconfidence to come off their medication.

Zidovudine is approved for use in those with symptomatic HIVdisease, early symptomatic disease with CD4 counts below 500/al,or symptom-free HIV-positive patients with CD4 counts below200/pl (or 500/ul and falling rapidly). A 1987 report on the efficacyof zidovudine in patients with AIDS or AIDS-related complex1ledto fast-track FDA approval. The UK and French Concorde trial,begun in 1988, on whether zidovudine delays the development ofsymptoms in healthy people infected with HIV, is still in progress,with a final analysis expected later this year. A Wellcome trial insymptom-free patients with CD4 counts of more than 400/pl hasrecently been terminated early after analysis revealed a significantreduction of disease progression.What evidence is there to support the change in attitude to a drug

whose supposed efficacy led to pressure from these same

organisations for its rapid passage through the Food and DrugAdministration (FDA) licensing procedures? Dispatches pointed toirregularities in the protocol of the trial that led to fast-track

approval. It revealed that an internal FDA report on this

Burroughs-Wellcome funded study, says that "treatment groupsunblinded themselves early" in the first few weeks, which "couldhave resulted in bias". The programme also drew attention totheoretical considerations that have led some to suggest thatzidovudine may not exert a specifically antiviral action. Dr PeterDuesberg-who is also the main proponent of the belief that HIV isnot the cause of AID S-argues that once an individual seroconvertsto HIV, viral replication probably ceases, thus removing the targetfor zidovudine’s action-namely, reverse transcriptase. This view isnot consistent with known data on antigenic drift in a single strain ofHIV in a given individual. The virus is constantly able to escape, bysmall changes to its antigenic profile, the neutralising antibodiesproduced in response to its presence. Viral replication will thereforeproceed, albeit at a low level, and zidovudine is likely to continue toact as a DNA chain terminator even after seroconversion. Severalother criticisms are made in the programme. For instance, althoughWellcome’s product brochure states that "AZT improves both thequality and length of life", no firm data are yet available on eitherpoint. Moreover, they claim that "no life threatening toxicities areassociated with zidovudine", but Dispatches said that severe

cytopenias and its activity as a "potential carcinogen" (from anFDA report based on in-vitro data) might suggest otherwise (butthe data sheet does admit to chromosomal damage in in-vitrostudies of human lymphocytes as well as evidence of carcinogenicityin rodents) The makers of the Dispatches programme intend toforward their fmdings to the Medicines Control Agency.

Irrespective of how one interprets the scientific and clinical trialdata, there is clearly a growing concern among the HIV-positivecommunity that more open debate about these issues is neededbefore further treatment recommendations are given or new trialsare planned. The Channel 4 programme sought the views ofWellcome UK and investigators from the Concorde trial about thecurrent place of zidovudine in the management of HIV-positivesubjects. However, because the Broadcasting ComplaintsCommission found a previous programme by the same televisionproduction company to be both misleading and confusing (seeLancet Aug 31, p 566), both parties declined the invitation to discussthese concerns further.

1. Fischl MA, Richmann DD, Grieco MH, et al. The efficacy of 3’-azido-3’deoxythymidine, an inhibitor of HTLV III/LAV replication, in patients withAIDS or AIDS-related complex a double-blind placebo-controlled trial. N Engl JMed 1987; 317: 185-91.

Disposal of previable fetuses

A stillborn baby must be formally buried or cremated, andunused embryos created in vitro must be disposed of "sensitively".But hospitals have no obligation to make special arrangements forthe disposal of the dead fetus between the embryo stage covered bythe 1990 Human Fertilisation and Embryology Act (up to 14 daysfrom fertilisation) and the legal gestational age of viability (28 weeksat present but likely to be reduced to 24 in forthcoming legislation).Many parents who have lost a baby before the legal age of stillbirthare distressed to find that their loss is scarcely acknowledged byhealth professionals. Parents need to know that the dead fetus isdisposed of respectfully and to have a choice about the means ofdisposal. Few, presumably, would opt for the hospital incinerator,yet a quarter of hospitals responding to a postal survey carried outby the Stillbirth and Neonatal Death Society (SANDS) said thatthey incinerated at least some pre-28-week fetuses along withhospital waste. Last year the NHS Management Executive issuedtwo circulars requesting hospital managers to satisfy themselvesthat their disposal arrangements are acceptable, and SANDS hasnow issued recommendations for good practice in the disposal ofsmall babies’ bodies or remains. I

The main recommendations are that parents should be offeredchoices about what is done and that the remains of all previablefetuses should be disposed of in a respectful and dignified way,irrespective of gestational age or how the loss occurred. If there is anidentifiable body, burial or cremation, and possibly a religious ornon-religious ceremony, should be offered. If there is no

identifiable body-for instance, after a miscarriage or

termination-the remains should be committed to the hospitalincinerator separately from hospital waste and under the

supervision of an appointed member of staff. The guidelines urgehospital staff to be imaginative, flexible, and responsive to parents asindividuals. Parents should also be given written information abouthospital policy and procedures and the choices available. Hospitalstaff may find disposal the most distressing aspect of dealing withpregnancy loss, and they should be given support and trained tohelp the bereaved parents.Some health professionals have expressed concern that parents

will be hindered rather than helped in their grieving by an"overzealous" approach to pregnancy loss, but in SANDS’

experience parents’ requests "are almost always reasonable, usuallyvery modest, and rarely inappropriate". And resource demands, theorganisation says, "are minimal when compared with the distress ofparents whose needs go unmet... [and] who realise too late, that thehospital procedures they depended on were far from respectful".1. A dignified ending: recommendations for good practice in the disposal of the bodies

and remains of babies born dead before the legal age of viability. By Nancy Kohner.SANDS, 28 Portland Place, London WIN 4DE. £7.95 + £1 packing and postage.

Containment of drug-resistant malaria

How to contain drug-resistant falciparum malaria remains amajor challenge in tropical countries. An international meeting ofWorld Health Organisation personnel, technical experts, and healthworkers, held in Bangkok in November, produced three importantrecommendations on this subject.

Firstly, in areas where chloroquine-resistant malaria isseen as a threat serious consideration should be given to

exploring combination chemotherapy (eg, quinine and tetracycline;sulphadoxine and pyrimethamine; mefloquine and tetracycline;mefloquine and sulphadoxine and pyrimethamine) in the first

instance, rather than after resistance to monotherapy becomeswidespread. This approach may improve treatment efficacy forindividual patients, could prevent or delay the spread ofmultiresistant strains of Plasmodiumfakiparum, and seems sensibleby analogy with what is known about tuberculosis. A degree ofpre-existing resistance to one or other drug may not preclude itsusefulness in combination therapy.

Secondly, many studies have shown that cure rates can be greatlyimproved by adding a tetracycline to the drug regimen. There is alsoevidence, as yet unconfirmed, that the emergence of resistant strainsmight be curtailed by this means. An evaluation of the use ofdoxycycline in this context might be especially appropriate;