VIRUSMYTH HOMEPAGE
THE HAYMAN CASE
Particulars of Plaintiffs’ Claim
1 June 2001
PRINCIPAL PARTIES
1.
First Plaintiff is Annet Hayman, an adult female widowed schoolteacher, born on 1 February 1960, who resides at 45A Residency Road, Ladysmith, KwaZulu-Natal.
2.
Second Plaintiff is Annet Hayman, an adult female widowed schoolteacher, acting in her capacity as mother and guardian of David Hayman, a minor male child born on 10 April 1995 (hereinafter referred to as the minor child) both of whom reside at 45A Residency Road, Ladysmith, KwaZulu-Natal.
3.
First Defendant is Glaxo Wellcome South Africa (Pty) Ltd, trading as GlaxoSmithKline, an incorporated company with limited liability registered under the company laws of South Africa under Registration No 1948/030135/07, carrying on business in the supply of pharmaceutical products, whose principal place of business is at 44 Old Pretoria Road, Midrand, Gauteng, hereinafter referred to as Defendant.
INTERESTED PARTIES
4.
Second Defendant is Thabo Mbeki, in his capacity as President of the Republic of South Africa, Office of the Presidency, Union Buildings, Pretoria, Gauteng.
5.
Third Defendant is Dr Manto Tshabalala-Msimang, in her capacity as Minister of Health, Department of Health, Union Buildings, Pretoria, Gauteng.
6.
Fourth Defendant is Professor Peter Eagles, in his capacity as President of the South African Medicines Regulatory Authority, 12th Floor, Hallmark Building, Cnr. of Proes and Andries Streets, Pretoria, Gauteng.
7.
No relief is claimed against Second, Third and Fourth Defendants, who are joined in this action for what interest they might have in the determination of the issues pleaded in paragraphs 9 to 22 - Second Defendant, having regard to his public statements in Parliament and other fora concerning both the toxicity and efficacy issues pleaded in this action; Third Defendant, having regard to similar public statements concerning the toxicity issue; and Fourth Defendant, having regard to the public responsibilities he bears in his cited capacity.
DECEASED’S DUTY OF SUPPORT
8.
8.1 At the time of his death, the late James Hayman, an attorney of Ladysmith, KwaZulu-Natal, hereinafter referred to as the deceased, was married to First Plaintiff.
8.2 The minor child was born of the marriage between First Plaintiff and the deceased.
8.3 During his lifetime, the deceased owed both First Plaintiff and the minor child a duty of support, and did in fact support them.
DEFENDANT’S PRODUCT, PRODUCT DESCRIPTION AND DUTIES OF CARE
9.
At all material times hereto:
9.1 Defendant supplied the chemical 3’-azido-3’-deoxythymidine, generically named zidovudine, formerly azidothymidine abbreviated to and commonly referred to as AZT, categorised as a nucleoside analogue reverse transcriptase inhibitor, under the proprietary name RETROVIR (hereinafter referred to by Plaintiffs as AZT) in capsules to pharmaceutical wholesalers and/or retailers in South Africa, intending it for oral consumption by members of the South African public as a pharmaceutical drug on prescription by medical practitioners;
9.2 Defendant published a written advisory which it supplied with AZT, a copy of which is annexed hereto marked "A" and hereinafter referred to as the package insert, in which its indications for use, claims about the drug’s pharmacokinetics and efficacy, and statements about its side effects were set out for the information of pharmacists dispensing it, medical practitioners prescribing it and their patients taking it;
9.3 Defendant was under a duty of care to members of the South African public including Plaintiffs and the deceased:
9.3.1 not to misrepresent the pharmacological action of AZT by making claims about it that had been disproved, alternatively, were unproven;
9.3.2 not to make claims of efficacy for AZT that had been disproved, alternatively, were unproven;
9.3.3 not to make unsafe and ineffective dose recommendations for AZT;
9.3.4 to properly and adequately describe AZT’s ill effects and hazards;
9.3.5 to warn prominently against AZT’s potentially life-threatening toxicities; and,
9.3.6 generally, not to supply any chemical substance for medicinal ingestion whose proven life-threatening toxicities were not outweighed by proven efficacy and clinical benefits, i.e. an unreasonably dangerous and defective drug.
TREATMENT OF THE DECEASED WITH AZT AND HIS DEMISE
10.
10.1 Towards the end of July 1997 and in Ladysmith, KwaZulu-Natal, the deceased commenced a month’s course of AZT, together with a related drug, 3TC, at daily oral doses of 600mg and 300mg respectively, which had been prescribed to him following an HIV-positive diagnosis based on reactive antibody tests for HIV, and a low CD4+ cell count.
10.2 When he commenced treatment with AZT, the deceased weighed 68kg, was not sick and presented with no symptoms of any illness.
10.3 The AZT treatment immediately made the deceased very ill, causing intractable diarrhoea and vomiting, intense headache, profound lassitude, anaemia, muscle weakness with cramps and pain, and progressive weight loss.
10.4 The severity of the drug’s ill effects experienced by the deceased led him to lower the dose of his own accord and thereby extend the month’s course of treatment over about two months.
10.5 The deceased declined a second course of AZT, but the ill effects of the first course failed to resolve.
10.6 The deceased was subsequently hospitalised on three occasions for uncontrollable diarrhoea and vomiting without any specific infectious aetiological agent being detected on pathological investigation, continued to suffer profound fatigue, continued to suffer muscular weakness and deterioration, and lose muscle mass and body weight, and finally died in Ladysmith, KwaZulu-Natal on 8 June 1998 weighing 42 kg.
10.7 The deceased died as a direct result of the cellular toxicity of AZT.
DEFENDANT’S CLAIMS FOR AND ABOUT AZT
11.
Defendant claims in the package insert:
11.1 Under the heading "INDICATIONS":
11.1.1 "RETROVIR Oral Formulations are indicated for the management of certain patients with Human Immunodeficiency Virus (HIV)."
11.1.2 "Evidence of efficacy has been demonstrated (sic) in adult patients with T4 (T-helper) [i.e. CD4+] cell counts of less than 500/mm3 whether or not associated with symptoms."
11.2 under the heading "PHARMACOLOGICAL ACTION" that:
11.2.1 "Zidovudine is an antiviral agent active in vitro against retroviruses including the Human Immunodeficiency Virus (HIV)";
11.2.2 "Zidovudine is phosphorylated in both infected and uninfected cells to the monophosphate (MP) derivative by cellular thymidine kinase. Subsequent phosphorylation of zidovudine MP to the diphosphate and then the triphosphate (TP) derivative is catalysed by cellular thymidylate kinase and non-specific kinases respectively";
11.2.3 "Zidovudine-TP acts as an inhibitor of, and substrate for, the viral reverse transcriptase";
11.2.4 "The formation of further proviral DNA is blocked by incorporation of zidovudine-TP into the chain and subsequent chain termination";
11.3 under the heading "WARNINGS" that "RETROVIR is not a cure for HIV infection and patients remain at risk of developing illnesses which are associated with immune depression, including opportunistic diseases and neoplasms. Whilst it has been shown to reduce the risk of opportunistic infections, data on the development of neoplasms, including lymphomas, are limited";
11.4 under the heading "DOSAGE AND DIRECTIONS FOR USE" and "Dosage in adults" that "A broad range of dosages (between 500mg and 1500 mg/day) have been used. 500mg or 600mg/day in two to five divided doses has been commonly used worldwide. Alternatively, a daily dosage of 1000mg in two divided doses has been shown to be effective."
12.
12.1 Defendant intended persons reading its claims in the package insert set out in paragraph 11 to understand that:
12.1.1 AZT is metabolised within human cells in vivo via the catalysing action of intracellular enzymes into its active form as an antiretroviral agent, AZT triphosphate (AZTTP), to levels sufficient for the activated drug to exert a virustatic action against HIV;
12.1.2 doses of AZT within the range recommended by Defendant result in optimal intracellular concentrations of AZT triphosphate in vivo;
12.1.3 AZT triphosphate blocks the reverse transcription of HIV RNA into proviral HIV DNA in the patient’s HIV-infected cells by being incorporated into growing proviral HIV DNA chains, thereby terminating proviral HIV DNA synthesis;
12.1.4 although not a cure, AZT has been shown to be an effective therapeutic or palliative antiviral drug for the treatment of HIV infection in asymptomatic adult patients with CD4+ cell counts of less than 500/mm3;
12.1.5 as an antiviral agent selectively inhibiting HIV RNA reverse transcription, AZT will reduce the number of cells infected with HIV, i.e. the level of the patient’s HIV infection;
12.1.6 the antiviral activity of AZT against HIV will limit the HIV-mediated depletion of the patient’s CD4+ immune cells, and thereby reduce the risk of the onset of opportunistic infections;
12.1.7 AZT is a beneficial drug that will extend the patient’s life, alternatively, enhance the quality of his life; and,
12.1.8 AZT has clinical benefits that outweigh its side effects.
12.2 Alternatively, given that Defendant supplies AZT for medicinal use, Defendant’s claims for and about AZT in the package insert set out in paragraph 11 have the reasonable meanings and/or implications pleaded in subparagraph 12.1.
DEFENDANT’S MODEL FOR THE ALLEGED PROVIRAL HIV DNA CHAIN TERMINATION ACTION AND CLINICAL BENEFIT OF AZT
13.
Defendant’s allegations in the package insert about the proviral HIV DNA chain termination action of AZT, and the drug’s clinical benefits, are based on the following model:
13.1 DNA is comprised of four nucleotides, one of which is thymidine.
13.2 AZT is a nucleoside analogue, a synthetic version of thymidine.
13.3 AZT differs from thymidine in that it has an azido (º
N) group in place of a 3’hydroxy (-OH) group.
13.4 The 3’hydroxy group functions as a link for nucleotides to attach themselves to growing DNA chains.
13.5 Because AZT has no 3’hydroxy group, if it joins a DNA chain in place of thymidine, no further nucleotides will be able to be attached to the DNA chain thereafter, and the further growth of the DNA chain will thus be terminated.
13.6 HIV is a retrovirus that directly or indirectly causes the depletion of CD4+ cells of the human immune system, thereby rendering the infected individual susceptible to the onset of certain opportunistic infections and malignancies known collectively as the Acquired Immune Deficiency Syndrome (AIDS).
13.7 HIV commences replication after entering a permissive cell with the reverse transcription of HIV RNA into proviral HIV DNA, a process catalysed by the retroviral enzyme reverse transcriptase, whereafter proviral HIV DNA becomes integrated into host DNA.
13.8 By terminating the generation of proviral HIV DNA, AZT triphosphate blocks HIV replication and interrupts the cycle of new cellular infection by HIV.
13.9 AZT triphosphate is effective against HIV during replication (i.e. the reverse transcription of HIV RNA into proviral HIV DNA), but not during HIV expression from already infected cells in which proviral HIV DNA has been integrated into host cell DNA (i.e. the process in which proviral HIV DNA is transcribed into HIV RNA, which then codes for the formation of viral proteins and the assembly of new viral particles) nor against cell-free HIV particles.
13.10 Viral burden (number of copies of proviral HIV DNA), viral load (number of copies of HIV RNA), HIV isolation (detection of reverse transcriptase, and/or p24 protein in cell cultures), and p24 antigenaemia (reaction of proteins present in patient sera with antibodies to HIV protein p24) are all measurable parameters that directly reflect the level of HIV infection, and thus indicate the efficacy or otherwise of a given drug as an antiretroviral medicine to the extent that the drug reduces them.
13.11 Due to the high rate of HIV replication from the onset of infection, and the fact that infected CD4+ cells have a life of only a few days, the chain terminating action of AZT against proviral HIV DNA synthesis, blocking HIV replication, will rapidly result in:
13.11.1 decreasing formation of proviral HIV DNA i.e. falling viral burden; and thus to:
13.11.2 a decrease in HIV RNA i.e. falling viral load, and thus to:
13.11.3 decreasing frequencies of HIV isolation (detection of reverse transcriptase or p24 or both in cell cultures) and decreasing levels of HIV p24 antigenaemia; and,
13.11.4 a direct correlation between all of these declining parameters, which will fall to low or absent levels.
AZT TRIPHOSPHORYLATION
14.
14.1 Defendant supplies AZT unphosphorylated.
14.2 In its native or parent form as a pro-drug, unphosphorylated AZT is incapable of antiretroviral activity against HIV.
14.3 In order to exert its intended action within cells as an antiretroviral agent, AZT must be converted by intracellular enzymes into its active form, AZT triphosphate, by the sequential addition of three phosphate groups.
14.4 AZT cannot substitute for natural thymidine in a growing proviral HIV DNA chain, and thereby terminate it, unless it has been triphosphorylated.
14.5 Neither unphosphorylated AZT, nor AZT monophosphate, nor AZT diphosphate, nor any other AZT metabolite are able to act as proviral HIV DNA chain terminators, and these forms of the drug are incapable of an anti-HIV effect.
14.6 Only the triphosphorylated form of AZT can inhibit HIV RNA retrotranscription by binding to growing proviral HIV DNA chains and terminating them, and thereby stop HIV replication.
15.
15.1 In November 1986 Furman and others including researchers from Wellcome Research Laboratories determined that in ideal in vitro conditions, using a synthetic RNA template (bearing no relation to HIV RNA) and purified reverse transcriptase (instead of HIV-infected cells), the IC50 value for AZT triphosphate against HIV reverse transcriptase, i.e. the minimum necessary ‘inhibition concentration’ of triphosphorylated AZT required to reduce the synthesis of HIV DNA from HIV RNA by half and thereby exert a virustatic effect, is 0.7 micromolar, i.e. a concentration of 0.7 picomoles of AZT triphosphate per million cells (Proceedings of the National Academy of Sciences of the United States of America 1986; 83: 8333-7).
15.2 In the much more complex milieu in vivo, where AZT triphosphate must compete with natural nucleotides for binding to growing HIV DNA chains, and for the reasons indicated by the limitations of Furman’s experimental design and execution mentioned in parentheses in subparagraph 15.1, a much higher concentration of AZT triphosphate will be necessary to effectively inhibit HIV RNA retrotranscription.
16.
16.1 Between 1991 and 2001, sixteen studies published in the scientific literature, and tabulated in annexure "B" hereto, investigated and reported the level to which AZT is triphosphorylated in vivo.
16.2 Apart from the first two studies (Toyoshima et al and Kuster et al) both of which employed experimental assays shown later not to have been properly validated (Slusher et al), all these studies reveal that AZT is triphosphorylated insignificantly in vivo, the best designed and executed of which indicate AZT to be triphosphorylated in vivo to levels one or more orders of magnitude below the drug’s IC50 value, as determined by Furman et al in ideal in vitro conditions.
16.3 Consistent with findings made in earlier studies in vitro that no relationship exists between AZT concentration and the level of phosphorylated AZT, or the total phosphate level, or the triphosphate level, one of the studies, Barry et al 1996, established that due to a saturation effect, 300mg doses of AZT taken twice daily did not result in better intracellular concentrations of AZT triphosphate in vivo than 100mg doses employed in the experiment.
16.4 The said studies refute Defendant’s express, alternatively, implied claim in the package insert that at oral doses within the range recommended by Defendant, AZT is triphosphorylated by intracellular enzymes in vivo optimally and sufficiently for it to block proviral HIV DNA formation, and thereby have an antiretroviral effect against HIV.
16.5 In the premises, taken orally as a medicine, AZT is incapable of an anti-HIV action.
AZT EFFICACY
EFFECT OF AZT ON HIV DNA (VIRAL BURDEN)
17.
17.1 All studies of the effect of AZT on HIV DNA levels reported in the scientific literature have revealed that AZT administered either alone or in combination with other drugs to HIV-positive individuals does not reduce levels of proviral HIV DNA.
17.2 The findings in these studies:
17.2.1 refute Defendant’s claims about the pharmacokinetics of AZT as a medicine made in the package insert that:
"The formation of further proviral DNA is blocked by incorporation of zidovudine-TP into the chain and subsequent chain termination (sic)" and, "Zidovudine-TP acts as an inhibitor of, and substrate for, the viral reverse transcriptase"; and,
17.2.2 establish that in vivo AZT:
17.2.2.1 has no inhibitory effect on HIV RNA retrotranscription, i.e. does not terminate HIV DNA chain formation by blocking proviral HIV DNA synthesis from HIV RNA;
17.2.2.2 so does not prevent HIV replication; and,
17.2.2.3 has no antiviral action against HIV accordingly.
EFFECT OF AZT ON HIV RNA (VIRAL LOAD)
18.
18.1 According to leading American HIV experts Saag, Shaw and Coombs and their associates (Nature Medicine 1996; 2 (6): 625-9): "A three-fold or greater sustained reduction (>0.5 log) of the plasma HIV RNA levels is the minimal response indicative of an antiviral effect... [R]eturn of HIV RNA levels to pre-treatment values (or to within 0.3 - 0.5 log of the pre-treatment value), confirmed by at least two measurements, is indicative of drug failure."
18.2 According to the 1997 British HIV Association guidelines for antiretroviral treatment (Lancet 1997; 349:1086-1092): "If the viral load has not fallen by about 1 log 8-12 weeks after treatment initiation, consideration should be given to modify therapy."
18.3 All studies reported in the scientific literature in which the effect of AZT on HIV viral load in patients has been investigated have consistently established that AZT taken alone or in combination with other reverse transcriptase inhibitors is not able to induce a sustained decrease in the plasma HIV RNA level of >0.5 log (the American criterion for anti-HIV drug efficacy), much less 1 log (the British criterion).
18.4 By both the American and British criteria mentioned above, AZT fails to achieve "the minimal response indicative of an antiviral effect" and is therefore a "drug failure" i.e. ineffective as an antiviral medicine against HIV.
EFFECT OF AZT ON HIV ISOLATION (DETECTION OF REVERSE TRANSCRIPTASE AND/OR HIV P24 PROTEIN IN CELL CULTURES) AND ON P24 ANTIGENAEMIA
19.
19.1 All studies reported in the scientific literature which have investigated the effect of AZT on reverse transcriptase and/or p24 levels in cell cultures from HIV-positive individuals, and on p24 antigen levels in the sera of HIV-positive individuals, have established that AZT does not reduce these parameters.
19.2 The findings in these studies indicate that AZT has no effect on HIV infection levels in vivo and refute Defendant’s express, alternatively, implied claim that taken as a medicine, AZT is an antiviral agent active against HIV.
AZT’S CLINICAL EFFECTS
20.
20.1 Defendant’s claim about the efficacy of AZT for asymptomatic HIV-positive individuals set out in subparagraph 11.1.2 is based primarily upon ACTG 019, a clinical study of the effects of AZT administration on asymptomatic HIV-positive patients with CD4+ cell counts of below 500/mm3 (New England Journal of Medicine 1990; 322:941-949).
20.2 The only proper manner in which the efficacy of a test drug can be determined epidemiologically is by conducting and completing a randomised, double-blind, placebo-controlled clinical trial.
20.3 The ACTG 019 study satisfied none of the requirements set out in subparagraph 20.2.
20.4 The results of the ACTG 019 study were disconfirmed by the only long term, large scale, prospective, randomised, double-blind, placebo-controlled investigation of the clinical effects of AZT for asymptomatic HIV-positive individuals yet conducted, the Concorde trial (Lancet 1994; 343:871-81), which found that:
20.4.1 CD4+ cell counts are unreliable as a surrogate marker for, and do not correlate with, clinical health;
20.4.2 AZT administration has no therapeutic benefits when administered to asymptomatic HIV-positive patients, and;
20.4.3 the extended results of the study showed "a significant increased risk of death among the patients treated early" i.e. among asymptomatic HIV-positive patients (New England Journal of Medicine 1997; 336:958-9).
20.5 The results of the Concorde trial refute Defendant’s express, alternatively implied claim in the package insert set out in subparagraph 11.1.2, that AZT is efficacious for asymptomatic HIV-positive individuals with CD4+ counts below 500 per mm3.
AZT TOXICITY
21.
21.1 Defendant claims in the package insert under the heading "PHARMACOLOGICAL ACTION" that "Competition by zidovudine-TP for HIV reverse transcriptase is approximately 100-fold greater than for cellular DNA polymerase alpha."
21.2.1 Defendant intended persons reading its claim set out in subparagraph 21.1 to understand that at recommended doses, AZT is not dangerously poisonous to human cells, and does not significantly disrupt human cell division and replication.
21.2.2 Alternatively, the reasonable meaning or implication of Defendant’s claim set out in subparagraph 21.1 is that pleaded in subparagraph 21.2.1.
21.3 Defendant states without elaboration in the package insert under the sub-heading "Haematological side-effects", i.e. AZT blood cell toxicity, that:
"The following events have been reported in patients treated with RETROVIR. […] myopathy […]", i.e. muscle disease characterised by weakness and wasting.
21.4 Numerous research investigations reported in the medical and scientific literature have established that:
21.4.1 AZT is a potent oxidising agent;
21.4.2 although insignificantly triphosphorylated intracellularly, AZT is readily monophosphorylated by cellular enzymes in vivo, to levels approximately 100-fold greater than AZT triphosphate levels, and with an efficiency and at a rate comparable with that of its natural analogue, thymidine;
21.4.3 the intracellular monophosphorylation of AZT inhibits the phosphorylation of cellular nucleotides;
21.4.4 the global reduction of natural triphosphorylated nucleotides available during cell mitosis, and the consequent perturbation of nucleoside triphosphate pools within cells, inhibits human DNA formation and thereby reduces the generation of new cells, and;
21.4.5 at concentrations in vivo resulting from oral doses of AZT recommended by Defendant, AZT, its phosphorylates, and other metabolites and catabolites are:
21.4.5.1 profoundly cytotoxic and inhibit human cell proliferation;
21.4.5.2 acutely toxic to human cell mitochondria, and cumulatively so during even short periods of AZT administration, cause them oxidative damage, inhibit their replication, and functionally impair their ability to carry out oxidative phosphorylation and to synthesise ATP within hours of administration, resulting in mitochondrial myopathy which leads to muscle atrophy and wasting;
21.4.5.3 acutely toxic to muscle tissue within days of AZT exposure;
21.4.5.4 particularly toxic to cells with a high turnover rate such as epithelial cells lining the gut, and lethal to intestinal flora, thereby inhibiting nutrient absorption and causing diarrhoea and nausea;
21.4.5.5 potentially irreversibly toxic to human cells, in that the destructive toxicity of AZT is not necessarily alleviated by the cessation of AZT treatment;
21.4.5.6 potentially fatally poisonous to the patient on account of the toxicity of AZT to all human cells.
21.4.6 daily doses of 500mg of AZT cause serious toxic ill effects that are life threatening in some cases;
21.4.7 myopathy and wasting among HIV-positive individuals have occurred almost exclusively among those treated with AZT.
PARTICULARS OF DEFENDANT’S NEGLIGENCE
22.
22.1 The death of the deceased was brought about by Defendant’s wrongful and negligent act in supplying him with an unreasonably dangerous and defective drug, and doing so on the basis of false and misleading representations contained in the package insert, set out in paragraph 11 and subparagraph 21.1, in that AZT:
22.1.1 cannot be and is not metabolised by human cells in vivo into its active triphosphorylated form to the minimum intracellular concentration necessary for the drug to exert its putative pharmacological action as a nucleoside analogue terminator of proviral HIV DNA chain synthesis, irrespective of the oral dose at which it is taken;
22.1.2 is therefore unable to inhibit the reverse transcription of HIV RNA to HIV DNA and thereby prevent viral replication in vivo, and does not in fact do so according to all direct markers for this pharmacological activity;
22.1.3 has no antiretroviral action against HIV in vivo accordingly;
22.1.4 is extremely poisonous to all human cells;
22.1.5 has no proven anti-HIV effects in vivo countervailing against its proven profound cellular toxicity for patients taking it;
22.1.6 increases the risk of early death when taken by asymptomatic HIV-positive individuals, i.e. does not extend life but potentially shortens it.
22.2 Alternatively, the death of the deceased was occasioned by Defendant’s wrongful and negligent omission to properly and adequately warn the deceased in the package insert about AZT’s ill effects and hazards enumerated in subparagraph 21.4, and to warn the deceased prominently in the package insert that within the range of doses recommended by Defendant, AZT’s toxicities are potentially fatal.
PLAINTIFFS’ DAMAGES
LOSS OF SUPPORT
23.
As a result of Defendant’s negligence resulting in the death of the deceased, Plaintiffs lost their right of support from the deceased and have suffered damages, calculated in the actuarial report annexed hereto marked ‘C’, as follows:
First Plaintiff: R824 170-00;
Second Plaintiff: R430 982-00.
PSYCHIATRIC INJURY
24.
24.1 As the deceased’s myopathy and the general systemic effects of his intoxication by AZT worsened, he progressively declined physically to the point where he became bedridden, unable to retain food in his gut, incontinent, prone to bouts of extended uncontrollable vomiting, and unable to feed himself, bathe himself, walk without assistance, pick himself up when he fell, and speak without slurring.
24.2 With the support of other caregivers, First Plaintiff nursed the deceased on her return from work each day throughout his illness until his death.
24.3 First Plaintiff’s experience of observing the toxic effects of AZT on the deceased, and the reduced physical condition in which the drug caused him to die, resulted in her suffering traumatic psychiatric emotional shock.
24.4 The psychiatric injury that First Plaintiff suffered resulted in her lapsing into deep depression for about two years after his death.
24.5 First Plaintiff’s depression periodically caused her to become psychologically indisposed, rendering her professionally incapacitated.
24.6 First Plaintiff was medically treated throughout her depression with antidepressant medication, and she was booked off work several times for weeks at a time due to her indisposition and to enable her to psychologically recuperate.
24.7 The psychiatric injury and consequent indisposition suffered by First Plaintiff, alternatively, the general nature of her psychiatric injury and indisposition, was a direct and reasonably foreseeable consequence of Defendant’s wrongful and negligent supply of AZT to the deceased.
24.8 As a consequence of her traumatic psychiatric emotional shock, First Plaintiff has suffered general damages of R100 000-00.
25.
In the premises Defendant is liable to compensate Plaintiffs for their aforesaid damages, but has repudiated liability and their claims remain unpaid.
WHEREFORE Plaintiffs claim judgment against Defendant as follows:
In favour of First Plaintiff:
(a) Payment of R924 170-00;
In favour of Second Plaintiff:
(b) Payment of R430 982-00;
(c) Interest on the aforesaid amounts at the prescribed legal rate, reckoned from the date of service of summons to date of payment;
(d) Costs of suit.
Dated at Pietermaritzburg on this 1st day of June 2001.
Signed by:
C J HARTZENBURG SC
Plaintiffs’ Counsel
A R BRINK
Plaintiffs’ Counsel
R J F STRETCH
Plaintiffs’ Attorney
LISTER AND LISTER
11th Floor UBS Building
Longmarket Street
PIETERMARITZBURG
Ref: Mr Stretch
Tel: 0331-3454530;
0827761481.
Annexure ‘A’
(Photocopy AZT package insert)
Annexure ‘B’
Triphosphorylation of AZT in vivo.
|
|
Year |
Peak concentrations of AZT triphosphate reported |
Reference |
|
1991 |
0.5 pmol/106 cells |
Kuster H, et al. J Infect Dis; 164: 773 - 776 |
|
1991 |
56 pmol/107 cells
(5.6 pmol/106 cells) |
Toyoshima T, et al. Analytical Bioch; 196: 302 - 307 |
|
1992 |
0.14 pmol/106 cells |
Slusher JT, et al. Antimicrob Agents & Chemoth: 2473 - 2477 |
|
1994 |
326 fmol/106 cells
(0.326 pmol/106 cells) |
Robbins BL, et al. Antimicrob Agents Chemother: 115 -121 |
|
1994 |
0.06 pmol/106 cells |
Barry MG, et al. AIDS; 8: F1 - F5 |
|
1996 |
95 fmol/106 cells
(0.095 pmol/106 cells) |
Rodman JH, et al. J Infec Dis; 174: 490 - 499 |
|
1996 |
0.069 pmol/106 cells |
Peter K, et al. J Pharm & Biomed Anal; (14): 491 - 499 |
|
1996 |
0.042 pmol/106 cells (average) |
Peter K and Gambertoglio JC. Clin Pharmacol Ther; 60: 168 - 176 |
|
1996 |
0.07 pmol/106 cells |
Barry MG, et al. AIDS: 1361 - 1367 |
|
1998 |
0.046 pmol/106 cells, in mononuclear cells from lymph nodes.
0.085 pmol/106 cells, in PBMC |
Peter K et al. AIDS: 1729 - 1731 |
|
1998 |
160 fmol/106 cells (average)
(0.16 pmol/106 cells) |
Fletcher CV, et al. Clin Pharmacol Ther 64: 331 - 338 |
|
1998 |
0.07 pmol/106 cells |
Robbins BL, et al. Antimicrob Agents Chemother: 2656 - 2660 |
|
1998 |
0.13 pmol/106 cells |
Phiboonakit DA, et al. Br J Clin Pharmacol 46: 294P -295P |
|
1999 |
193 fmol/106 cells
(0.193 pmol/106 cells) |
Font E, et al. Antimicrob Agents Chemother: 2964 -2968 |
|
2000 |
0.14 pmol/106 cells |
Wattanagoon Y, et al. Antimicrob Agents Chemother: 1986 -1989 |
|
2001 |
0.14 pmol/106 cells |
Hoggard P, et al. Antimicrob Agents Chemother: 976-980 |
Notes:
1 mole (mol) is a quantity of 6.02 x 1023 molecules; 1 micromolar (m
M) is a concentration of 1 micromole (m
mol) per litre; 1m
mol = 10-6 moles; 1 pmol = 10-12 moles; 1 fmol = 10-15 moles; 1 pmol/106 cells =1m
M.
Much of the data on AZT triphosphorylation in vivo, inefficacy, and toxicity pleaded in this action is reviewed by Papadopulos-Eleopulos et al in A Critical Analysis of the Pharmacology of AZT and its Use in AIDS. Current Medical Research and Opinion (1999) Volume 15, Supplement 1. The paper is listed in Current Contents, MEDLINE, EMBASE/Excerpta Medica and other major databases, and is archived by Librapharm online at: www.librapharm.co.uk/cmro/vol_15/supplement/main.htm. Following submission of the paper for peer-review in 1998 and its acceptance for publication on 1 December 1998 and publication on 1 September 1999, further studies investigating AZT triphosphate levels in vivo and the effect of AZT on HIV DNA and HIV RNA reported findings consistent with those reviewed. The extensive corpus of clinical reports and research investigations concerning AZT myopathy published to date has not yet been systematically reviewed in any professional literature. However a summary of these papers is presented for a lay readership in Debating AZT: Mbeki and the AIDS drug controversy by A R Brink (ISBN 0 620 26177 3).
VIRUSMYTH HOMEPAGE