Zidovudine, ZDV, Retrovir® etc.

"At present, data regarding the effects of ZDV use on vertical transmission rates are inconclusive and incomplete. In addition, the long-term effects of ZDV use during pregnancy and after birth on the woman and any resulting child are yet to be discovered... the possibility has not yet been ruled out that this "risk-reducing" measure may not be effective and may prove detrimental to the health of both mother and child."

Bennett , Mandatory Testing of pregnant women and newborns: a necessary evil? AIDS/STD Health Promotion Exchange 1998

" adult mice, lifetime AZT administration induces vaginal tumors at a 10-20% incidence... In newborn monkeys and mice, AZT was incorporated into DNA of many fetal tissues... AZT appears to be a moderately-strong transplacental carcinogen [i.e. it crosses the placenta and may cause cancer in the fetus]"

Olivero et al , AZT is a Genotoxic Transplacental Carcinogen in Animal Models, Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 1997, 14(4): A29.

"The concentrations of the drug [AZT] in the liquor and in the fetal blood [of 6 aborted human fetuses] were higher or equaled those found in the maternal blood... The drug remains contra-indicated in pregnancy."

Gillet et al , Preliminary study on the transport of AZT (Retrovir-zidovudine) through the placenta, J Gynecol Obstet Biol Reprod, 1990; 19(2): 177-180.

"AZT... induces significant toxic effects in humans exposed to therapeutic doses... Cytogenetic observations on H9-AZT cells showed an increase in chromosomal aberrations and nuclear fragmentation when compared with unexposed H9 cells... The toxicities explored here suggest that the mechanisms of AZT induced cytotoxicity in bone marrow of the patients chronically exposed to the drug in vivo may involve both chromosomal and mitochondrial DNA damage."

Agarwal & Olivero , Genotoxicity and mitochondrial damage in human lymphocytic cells chronically exposed to [AZT], Mutat Res, 1997; 390(3): 223-231.

"The incidence of adverse reactions [to AZT] appears to increase with disease progression, and patients should be monitored carefully, especially as disease progression occurs. [i.e. AZT does not prevent progression to AIDS]... The long-term consequences of in-utero and infant exposure to zidovudine [AZT] are unknown. The long-term effects of early or short-term use of zidovudine in pregnant women are also unknown."

Retrovir, Canadian Pharmaceutical Association Compendium of Pharmaceuticals. 1997; 1357-1361.

"It was often difficult [in AZT clinical trials] to distinguish adverse events possibly associated with administration of Retrovir [AZT] from underlying signs of HIV disease or intercurrent illnesses [i.e. AZT can cause AIDS-defining illnesses]."

Retrovir, Physician's Desk Reference, Mosby-Year Book Inc., 1996.

"Extended follow-up of patients in one [AZT] trial, the Concorde study, has shown a significantly increased risk of death among the patients treated early."

Phillips et al, letter, NEJM, March 27, 1997.

"A total of 172 (96 Imm, 76 Def) participants died [169 while taking AZT, 3 while on placebo]"... The results of Concorde do not encourage the early use of zidovudine in symptom-free HIV-infected adults. They also call into question the uncritical use of CD4 cell counts as a surrogate endpoint for assessment of benefit from long-term antiretroviral therapy... Representatives of the Wellcome Foundation who were also members of the Coordinating Committee have declined to endorse this report."

Concorde Coordinating Committee, Concorde: MRC/ANRS randomised double-blind controlled trial of Immediate [Imm] and deferred [Def] zidovudine in symptom-free HIV infection, The Lancet, Vol 343, April 9, 1994.

"In reviewing the frequency of birth defects in this population [of HIV+ women taking AZT during pregnancy] we noted eight birth defects (10%) out of 80 live births."

Kumar et al, Zidovudine Use in Pregnancy: A Report on 104 Cases and the Occurrence of Birth Defects. Journal of the Acquired Immune Deficiency Syndrome 7:1034, July 1994.

"Blood transfusion is often necessary in patients with AIDS, especially in those receiving AZT, a drug which produces severe anaemia in a proportion of recipients. Forty nine (36%) of 138 patients treated with AZT... required blood transfusion at least once."

Costello, Haematological abnormalities in human immunodeficiency virus (HIV) disease, Journal of Clinical Pathology. 1988; 41: 711-715.

"While effective drug therapy is continued in zidovudine[AZT]-treated HIV-infected patients... PROCRIT Reduces Transfusion Requirements and Helps Lift the Burden of Anemia."

Advertisement for PROCRIT, 1997.

"Anaemia [during AZT therapy] appears to be due to bone marrow suppression..."

Dainiak et al, 3'-Azido-3'-deoxythymidine (AZT) inhibits proliferation in vitro of human haematopoietic progenitor cells, British Journal of Haematology. 1988; 69: 299-304.

"It is worrying that bone marrow changes in patients on zidovudine seem not to be readily reversed when the drug is withdrawn... These findings have serious implications for the use of zidovudine in HIV positive but symptom-free individuals."

Mir & Costello, Zidovudine and Bone Marrow, The Lancet. 1988; 1195-1196.

"Four patients with the acquired immunodeficiency syndrome, and a history of Pneumocystis carinii pneumonia developed severe pancytopenia... 12 to 17 weeks after the initiation of azidothymidine (AZT) therapy... Partial bone marrow recovery was documented within 4 to 5 weeks [after discontinuation of AZT] in three patients, but no marrow recovery has yet occurred in one patient during the more than 6 months since AZT treatment was discontinued."

Parkash et al, Azidothymidine [AZT] Associated with Bone Marrow Failure in the Acquired Immunodeficiency Syndrome (AIDS), Annals of Internal Medicine. 1987; 107: 502-505.

"The AZT animals [Macaques given AZT during pregnancy] developed an asymptomatic macrocytic anemia, but hematologic parameters returned to normal when AZT was discontinued. Total leukocyte count decreased during pregnancy and was further affected by AZT administration. AZT-exposed infants were mildly anemic at birth. AZT caused deficits in growth, rooting and snouting reflexes, and the ability to fixate and follow near stimuli visually"

Ha JC et al., Fetal, infant, and maternal toxicity of zidovudine (azidothymidine) administered throughout pregnancy in Macaca nemestrina. J Acquir Immun Defic Syndr Hum Retro; 18: 27-38.

"...the estimated probability of developing [Non-Hodgkin] lymphoma [in patients taking AZT alone, or in combination] by 30 months of therapy was 28.6%... and by 36 months, 46.4%."

Pluda et al, Development of Non-Hodgkin Lymphoma in a Cohort of Patients with Severe Human Immunodeficiency Virus (HIV) Infection on Long-Term Antiretroviral Therapy, Annals of Internal Medicine. 1990; 113(4): 276-282.

"[AZT may] unmask silent opportunistic infections... Lack of strong evidence exists for sustained immune reconstitution by current therapies [AZT and other]."

Kelleher et al, Immunology, AIDS. 1997; 11 (suppl A): S149-S155.

(Thanks to David Crowe and Billy Goldberg)