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In the matter between

TREATMENT ACTION CAMPAIGN AND OTHERS                          Applicants

MINISTER OF HEALTH AND OTHERS                             Respondents


I, the undersigned

                            ROBIN WOOD

hereby make oath and state as follows:

1. I previously deposed to an affidavit in this matter.

2. The facts deposed to in this affidavit are again within my personal
   knowledge except where I indicate otherwise. To the extent that I
   rely on information supplied by others, I believe that such
   information is true and correct.

3. I have read the affidavits of Dr Ayanda Ntsaluba, Dr Princess
   Nothemba Simelela, Dr Jonathan Levin and Dr Philip Chukwuka
   Onyebujoh and respond to these affidavits to the extent that they
   deal with scientific and clinical matters pertaining to the reduction
   and prevention of mother-to-child transmission of HIV.


4. Dr Ntsaluba (ad paras 19 and 45) and Dr Simelela (ad para 76)
   admit that HIV constitutes “a major public health problem” but they
   apparently dispute the relevance of the evidence in the antenatal-
   survey. This survey (also attached by the Respondents) illustrates
   that at least 2.5 million women aged 15-49 have HIV. The majority
   of the women are of reproductive age and will benefit from
   counseling, testing, advice on HIV and reproductive health,
   nutritional supplements, the provision of antiretroviral medicines
   such as Nevirapine to reduce mother-to-child HIV transmission,
   advice on breastfeeding and formula feed where appropriate.

5. As a clinician specialist working in the public sector, it is my
   opinion the facts contained in paragraph 11 of my original affidavit
   are relevant because an MTCT prevention programme including
   the use of Nevirapine is a health intervention needed by millions of
   women with HIV and their future offspring.

6. I disagree with the negative constructions of certain of the
   deponents for the Respondents regarding the safety, efficacy and

  resistance of a single dose Nevirapine for the reduction of mother-
  to-child HIV transmission, for the reasons set out below.


7. There is no medicine which does not have possible adverse
  effects. For example, I attach (RW 18) a package insert for
  Panado, a well-known medicine which can be bought over the
  counter in supermarkets, without prescription, to deal with fevers
  and pains. The list of possible adverse effects speaks for itself.

8. In deciding whether a medicine is safe, the question is therefore
  not whether a medicine has possible adverse side-effects. The
  question is the likelihood and severity of those side-effects.
  Regard must obviously also be had to the seriousness of the
  condition which it treats.

9. The World Health Organisation (WHO) unequivocally states in its
  recommendations that antiretrovirals such as Nevirapine are safe
  to use in mothers and infants to reduce intrapartum mother-to-child
  HIV transmission. On the “Safety of ARV prophylactic regimens” it
  says: “Conclusion: The WHO Technical Consultation concluded
  that benefit of these drugs in reducing mother-to-child HIV
  transmission greatly outweighs any potential adverse effects of
  drug exposure. “ This is contained at page 215 (RW17) of my
  orginal affidavit.

10.   Dr Simelela was a party to this consensus statement. Neither
  she nor Dr Ntsaluba has produced any evidence to the contrary.

11.   In her comment on the WHO Consensus statement, Dr
  Simelela misrepresents the position in her affidavit at paragraph
  113.5. She denies that the WHO Cunsultation considered the
  safety of Nevirapine for MTCT prevention. “The WHO was
  concerned with antiretroviral drugs in general and not only with
  Nevirapine. None of the clinical trials referred to by WHO in the
  paragraphs addressing safety of antiretroviral prophylactic
  regimens include trials where Nevirapine was used. The
  conclusion by the WHO Technical Consultation on safety does not
  apply, and cannot be applied, to Nevirapine. …” (emphasis added)
  This is not a mistake by Dr Simelela because she also refers to it
  in paragraphs 113.1 to 113.4.

12.   Where the WHO statement concludes: “Short-term safety and
  tolerance of the effective antiretroviral prophylactic regimens has
  been demonstrated in all the controlled clinical trials,1-4,6-8,10-12
  while collection of long-term safety data is ongoing”, it does in fact
  include Nevirapine. The following studies that address the use
  and safety of Nevirapine in clinical trials are referred to and
  prominently footnoted in the WHO statement:

  12.1.    Endnote 10: Owor M et al “The one year safety and

          efficacy data of the HIVNET 012 trial” 13th AIDS
          Conference, Durban South Africa 9-14 July 2000.
          Abstract LbOr1

  12.2.   Endnote 11: McIntyre J. et al “Evaluation of the safety of
          two simple regimens for prevention of mother-to-child
          transmission (MTCT) of HIV infection: Nevirapine (NVP)
          versus zidovudine (ZVD) + lamivudine (3TC) in prevention
          of peripartum HIV transmission, Abstract LbOr2, 13th
          International AIDS Conference, Durban, South Africa, 9-
          14 July 2000.

  12.3.   Endnote 8: Moodley, D et al The SAINT Trial: Nevirapine
          (NVP) versus zidovudine (ZVD) + lamivudine (3TC) in
          prevention of peripartum HIV transmission, Abstract
          LbOr2, 13th International AIDS Conference, Durban,
          South Africa, 9-14 July 20

  12.4.   Endnote 7: Guay L et al “Intrapartum and neonatal single
          dose nevirapine compared with zidovudine for prevention
          of mother to child transmission of HIV-1 in Kampala,
          Uganda: HIVNET 012 randomized trial” Lancet 1999;

13.   The HIVNET results by Owor et al concluded that the “Study
  results continue to indicate that a single dose of NVP given to
  HIV+ women in labor and to the newborn within 72 h of birth was

  safe and significantly reduced mother-to-child HIV transmission
  rate compared with a short course AZT regimen in a breast
  feeding population.”

14.   Even although the Respondents (through Dr Levin) have
  disputed the efficacy of Nevirapine in the SAINT Study, they have
  not questioned the safety data of that study.

15.   In a report on the SAINT study, Dr. Glenda Gray concluded
  that: “Both NVP and ZDV+3TC regimens were safe and well-
  tolerated and equally effective. She reports that “all potentially
  drug-related adverse events were rashes”. Of the 661 women
  enrolled for the study, only 7 or 1.2% had rashes. Only one
  woman had a rash that lasted 25 days. Of 649 infants 13 or 2.1%
  had rashes. Of these only “two infants had rash after NVP, one
  day after the dose.” (RW19)

16.   Dr Simelela herself acknowledges the efficacy and safety of
  Nevirapine at paragraph 29 of her affidavit, where she states:
  “Although the WHO technical consultation concluded that “the
  implementation of the ARV drug regimens (including Nevirapine)
  could be recommended for general implementation; the WHO
  recommendations only relate to the efficacy and safety issues of
  the drugs, but do not relate to the operational and implementation

17.   Background papers for the WHO Consultation were prepared
  by experts, and were presented in plenary sessions and discussed
  in groups at the Consultation. They included a paper by Dr. Lynne
  Mofenson (National Institute of Health, USA) and Dr. Paula
  Munderi (UN AIDS, Geneva) on “Safety of Antiretroviral
  Prophylaxis of Perinatal Transmission on HIV-Infected Pregnant
  Women and Their Infants” (RW20)

18.   This paper shows that Nevirapine safety was discussed, and it
  contains the following conclusion: “The Data and Safety
  Monitoring Board interim review of 869 mother/infant pairs in the
  study conducted earlier this year [2000] identified no safety
  concerns, with no significant difference identified between
  nevirapine and placebo groups in terms of rash, clinical,
  hematologic or liver toxicity in either women or infants.” Safety in
  women in the SAINT and HIVNET 012 was confirmed: “No woman
  receiving nevirapine had hepatic toxicity in either study; rash
  occurred in less than 2% of women in both studies and was non-
  serious in all cases. (Mofenson and Munderi page 17).

19.   In fact, the evidence presented by Dr Ntsaluba and Dr Simelela
  indicates that NVP is safe to use as long-term treatment in infants
  and children.

20.   The Medicines Control Council approved package insert states
  the following: “Paediatric Patients: Safety has been assessed in
  361 HIV-1 infected paediatric patients between the ages of 3 days

  to 19 years. … The most frequently reported adverse events
  related to Viramune [NVP] were similar to those observed in

21.   Dr Ntsaluba misrepresents facts presented in my original
  affidavit at paragraphs 24-26 and in the founding affidavit by
  Siphokazi Mthathi at paragraph 72-74. There I drew attention to
  serious potentially life-threatening adverse effects seen in a
  minority of patients who use NVP as long-term chronic medication
  in association with other antiretroviral agents. Together with the
  MCC, the WHO and other agencies nationally and internationally, I
  differentiate between long-term treatment and a single once-off
  dose with NVP.

22.   However, Dr Ntsaluba confuses the adverse effects of long-
  term treatment with prevention by a single-dose of NVP. At
  paragraph 56.3 of his affidavit he says: “Furthermore, even though
  the risk/benefit ratio of Nevirapine as an anti-retroviral agent has
  been found to be in favour of continued use of Nevirapine, serious
  safety issues have been picked up after registration of Nevirapine
  not only in South Africa but all over the world. … Although these
  undesirable effects are worse with prolonged use of Nevirapine,
  some of them especially skin reactions have the potential to occur
  with the first exposure to and the short-term use of Nevirapine in
  MTCT of the HIV.” (emphasis added)

23.   Later, Dr Ntsaluba repeats this allegation and says: “Thus far,
  serious safety issues pertaining to the use of Nevirapine have
  emerged, for example serious localised and systematic skin
  reactions, for example the Steven Johnson Syndrome,
  Anaphylaxis and Hepatitis. Although these problems are more of
  a risk with the continued use of Nevirapine, they are also likely to
  occur with short-term use of that medicine, for example in order to
  treat MTCT of HIV.” (excerpted from para 110.1.1)

24.   From the letter of the manufacturer of Nevirapine, Boehringer
  Ingelheim attached to Dr Ntsaluba’s affidavit (“AN8” pages 923-4),
  it is evident that the MCC and the manufacturer understand the
  severe adverse reaction to refer to treatment with Nevirapine as a
  chronic medication. For instance, it refers to the “first 8 weeks of
  therapy” with Nevirapine as the “critical period”. It is of course
  common cause that NVP used to reduce mother-to-child HIV
  transmission relies on a single dose to the mother and a single
  dose to the infant.

25.   Scientific logic would suggest that if a medicine is considered
  safe for long-term daily use, a single once-off dose would be much
  safer. That must be one of the reasons why the MCC endorsed
  the claim on the package insert that: “Pregnancy and lactation:
  The safety of Viramune [NVP] in pregnant or lactating women
  except when used as a single dose during labour has not been

26.   A similarly pragmatic and cautious approach is followed by the
  Respondents in their pilot research and training sites. At page
  1397-1398 and elsewhere in the affidavit of Dr Simelela, an
  informed consent form is attached. This form is used to counsel
  patients who participate in the government “research sites”. It
  reads: “There are side effects that can be expected from taking
  many tablets of Nevirapine. These are skin rash, fever, nausea,
  headache and abnormal liver functions tests. In this programme,
  you will receive only one tablet, and these side-effects have not
  been commonly reported for one dose.” (1397)

27.   In fact, as Mofenson and Munderi show, apart from non-serious
  rash, Nevirapine did not cause any adverse reactions when used
  to reduce mother-to-child HIV transmission.

28.   There can be no other scientific conclusion than to say that the
  MCC registered Nevirapine because on all the available evidence,
  it is safe to use for the reduction in risk of intrapartum transmission
  of HIV-1 from mother to child in patients who have been tested for
  HIV and appropriately counseled.


29.   In my previous affidavit, I expressed the opinion that the
  efficacy of Nevirapine to reduce mother-to-child HIV transmission
  during labour and at birth was established by two clinical trials,
  HIVNET 012 in Uganda and the SAINT trial in South Africa. I

  endorsed the statements of Ms Mthathi at paragraphs 57-71 of the
  her affidavit in this matter.

30.   Dr Ntsaluba agrees that Nevirapine is effective. He says: “It is
  further noteworthy that Nevirapine has been proven to be effective
  in intrapartum transmission of HIV-1. It has only been approved
  and licenced for this reason. Thus, Nevirapine does not address
  the other aspects of a comprehensive programme of prevention of
  MTCT of HIV.” (para 56.4)

31.   I agree with Dr Ntsaluba’s conclusion that Nevirapine is
  effective in reducing mtct HIV transmission intrapartum. However,
  I add that Nevirapine is also approved for the chronic treatment of
  HIV-1 in adults and children by the MCC.

32.   Dr Levin is of the same opinion. He states: “The efficacy of
  intrapartum and neonatal single dose Nevirapine (NVP) in the
  prevention of mother-to-child transmission (PMTCT) of the HIV
  was established by the HIVNET 012 randomised trial in Uganda.”
  He repeats this and states that: “HIVNET 012 provides conclusive
  evidence of the efficacy of Nevirapine.” (para 7)

33.   In November 2000, the National Steering Committee of the
  South African Programme for PMTCT, chaired by Dr Simelela,
  prepared its protocol for the research and training sites.   That
  document states: “The use of antiretroviral therapy to reduce
  mother to child transmission of HIV has become the standard

  treatment in developed countries. Recent results showing that the
  use of both short course AZT and single dose Nevirapine
  administered in labor to the mother and a dose to the infant can
  reduce transmission has led to recommendations for the
  widespread introduction of antiretroviral interventions for this
  strategy in developing countries, in parallel with the provision of
  replacement feeds. “ It continues further: “There is enough
  evidence to support the efficacy of antiretroviral drugs in the
  reduction of HIV transmission from mothers to infants.” (pages
  1265 and 1266 Simelela annexures)

34.   “General efficacy of Nevirapine not in doubt. Clinical
  effectiveness not the key objective of the pilot programme. “ This
  statement is made in a Department of Health presentation entitled
  “Developing a research framework for the National Pilot
  Programme for Prevention of Mother to Child Transmission of HIV”
  on 4th June 2001. It appears at page 1181 as an annexure to Dr
  Simelela’s affidavit.

35.   Dr Levin agrees that HIVNET012 showed that Nevirapine
  reduces intrapartum transmission by 47%, but only after a 6 to 8
  week period. He further states "it could be argued from a public
  health point of view that the month 20 result is more relevant than
  the 14-16 result."(para 7) Dr Levin ultimately concludes that: "NVP
  does reduce MTCT, but probably considerably less than the
  relative reduction of 50% as claimed by the Applicants." Dr Levin
  has conflated separate two interventions as I will explain below:

  35.1.    Nevirapine is effective for intrapartum transmission
           prevention and does reduce mother-to-child transmission
           by almost 50% with alternative feeding during the first
           weeks of life; and

  35.2.    Transmissions that occur post-partum are almost entirely
           due to breastmilk transmission. This can lead to
           significant reversals. The reversal can be reduced with
           the parallel provision of alternative feeds.

36.   Dr Ntsaluba acknowledges the WHO Consultation Consensus
  “that the long-term efficacy of short-term Nevirapine regimens has
  been demonstrated by infant status through 12-24 months.” (para

37.   Dr Levin (either in his capacity as a member of the MCC or
  some other capacity) has had access to SAINT data that is not in
  the public domain, and that he has not attached to his affidavit.
  He analyses the SAINT data and concludes that this trial cannot
  provide any “statistically” relevant evidence that Nevirapine is
  effective. Without access to this data, I cannot comment
  intelligently on his analysis. If the data is made available, I will be
  able to express a professional opinion on it.

38.   However, regardless of whether the SAINT study provides this
  evidence, I believe that it is indisputable (and apparently common

  cause) the HIVNET 012 study has prove the evidence of efficacy
  for reducing or preventing intrapartum transmission of HIV..


39.   The detection of a Nevirapine-resistant strain of HIV after a
  single dose in a minority of mothers and infants concerned every
  public health expert. Evidence from the different clinical trials
  showed however that every mother and infant who had resistant
  virus reverted to wild-type virus, thus allaying the concerns of
  public health experts. Therefore, the WHO Technical Consultation
  concluded that: “the benefit of decreasing mother-to-child HIV
  transmission with these antiretroviral drug prophylaxis regimes
  greatly outweighs concerns related to development of drug

40.   The WHO Consultation agreed the following:
      “Selection of resistant viral populations
      Selection for pre-existing resistant viral populations or
      development of new mutations may occur with all antiretroviral
      drugs or drug regimens that do not fully suppress viral
      replication. However, this is more likely to rapidly occur with
      drugs in which a single mutation is associated with
      development of drug resistance; such drugs include 3TC (with
      and without concomitant ZDV treatment) and Nevirapine.22-24
      Virus containing drug resistant mutations decreases in amount
      once antiretroviral drug prophylaxis is discontinued, and wild
      type virus dominates.25 However, the mutant virus may remain
      present in an individual at very low levels.

       This could decrease antiviral effectiveness of future
         treatment with antiretroviral regimens that contain the same
         drug, or drugs within the same class, as that used for
       It is unknown if such low-level drug resistance would affect
         the efficacy of the antiretroviral prophylaxis regimen if used
         in a subsequent pregnancy.
       There is currently no evidence that drug-resistant viruses are
         more transmissible than non-resistant viruses.
       There are currently no data to indicate that drug-resistant
         viruses are more virulent than non-resistant viruses.
      Conclusion: The WHO Technical Consultation concluded that
      the benefit of decreasing mother–to-child HIV transmission with
      these antiretroviral drug prophylaxis regimens greatly
      outweighs concerns related to development of drug resistance.
      (page 215-216 of record).

41.   Dr Ntsaluba and Dr Simelela repeatedly exaggerate the
  scientific and public health impact of Nevirapine-resistant virus.
  They use descriptions such as “catastrophic consequences”,
  “devastating”, “potentially catastrophic for public health”. There is
  no evidence of such impact or potential impact. If there had been,
  the WHO would not have made the recommendations which it did.

42.   The MCC has requested that the manufacturer of Nevirapine
  monitor the emergence of resistant virus. This is sensible and a
  step I would support.

43.   Dr Simelela states that “as part of the research and training
  programme the First to the Ninth Respondents have undertaken a
  prospective study of the selection of resistant variants of HIV-1
  following the use of intrapartum and post-partum Nevirapine

  therapy.” The plan is annexed as “NS6” and can be found at page
  1131 of the Respondents’ papers. This plan is commendable.

44.   The scientists and clinicians involved in this study state the
  following in Annexure NS6 (1131-1144):

  44.1.     HIV is genetically variable. It replicates at a very high rate:
            viral turnover in an infected individual is approximately 10
            billion viral particles per day.

  44.2.     The replication process is inaccurate and even without
            drugs it results in the generation of multiple variants of the
            original (“wild type”) strain.

  44.3.     Drug pressure exposes HIV to intense selective pressure.
            Viral strains that have “reduced susceptibility” to the drug
            “have a reproductive advantage and replicate”. Drug
            sensitive strains decrease.

  44.4.     When the viral population is no longer exposed to the
            antiretroviral (e.g. if therapy is halted), “wild type” strains
            become dominant again.

  44.5.     “Virus containing drug resistant mutations decreases in
            amount once antiretroviral drug prophylaxis is
            discontinued, and wild type virus dominates”.

  44.6.     Persistent Nevirapine resistant variants of HIV were not
            found in any of the women who received the drug as part
            of a mother-to-child programme.

  44.7.     Drug resistant HIV virus was not circulating in HIV-
            infected drug naïve women attending the ante-natal clinic
            at Chris Hani Baragwanath Hospital.

  44.8.     The Respondents’ study will only involve 200 women.

45.   These expert opinions are at variance with the claims of Dr
  Ntsaluba and Dr Simelela.

46.   I reiterate that there is a much greater public health danger in
  denying pregnant women and their infants Nevirapine, than in
  mass-scale provision.

47.   I have read the expert affidavit of Dr. Pierre Schoeman and
  agree with its analysis and conclusions.


48.   Reversals of all mother-to-child HIV prevention interventions
  occur in a breastfeeding population.

49.   In my previous affidavit, I said: “HIV can be transmitted from
  mother-to-child through breastmilk. Alternative feeding options

  such as formula feed reduce this risk. Since 1992, it has been
  recommended that where feasible, women be counseled to
  formula feed. However, breastfeeding is the cheapest and
  nutritionally most desirable way to feed infants. In poor
  communities women often do not have access to clean water or
  high-cost formula feed. In all contexts, women should be given the
  clear information to make informed choices and provided with
  formula feed when she chooses alternative feeding. “

50.   It is a tragedy that almost a decade after these facts were
  known, no systematic programme exists to ensure that safe
  alternatives to breastfeeding exist for women with HIV/AIDS, even
  leaving aside the question of an antiretroviral intervention.

51.   Women and their infants must be given a choice on feeding
  options that will promote their rights to healthcare and life.


52.   I appreciate the operational concerns faced by the
  Respondents’. After all, I am an employee in the public sector with
  expertise in developing programmes on Infectious Diseases.

53.   Because of its low cost; its proven safety and efficacy; and its
  relative ease of use, I believe that Nevirapine provides the public
  sector with an ideal opportunity to create the requisite

  infrastructure to use more complex regimens that will eliminate
  paediatric HIV infections.

54.   There are no easy answers to operational challenges. I urge
  the Respondents to adopt a two-fold incremental approach to
  create the capacity and operational conditions for such
  comprehensive programme:

  54.1.    First, adopt an incremental approach, that allows doctors
           and other health-care professionals to prescribe and
           administer Nevirapine anywhere in the public sector
           where capacity exists to counsel and where patients have
           given informed consent. This can be promoted in a clear
           policy guideline that does not undermine the Essential
           Drug List or impact negatively on the fiscus. It is only an
           interim solution.

  54.2.    Second, I urge the Respondents to plan and implement a
           comprehensive programme that will deal with among
           others the following:

      54.2.1.    A programme and budget for the training of health
                 care professionals;

      54.2.2.    A programme and budget for the training and
                 provision of counselors for VCT;

      54.2.3.     A programme and budget for HIV testing;

      54.2.4.     A programme and budget to provide the nutritional
                  supplements needed by pregnant women with

      54.2.5.     A programme for the acquisition of the dosages of
                  Nevirapine needed for women and their new-born
                  infants (currently available for free);

      54.2.6.     A programme and budget for the formula feed
                  needed by women who choose this alternative.
                  This could also include a plan to reduce the cost of
                  formula feed;

      54.2.7.     A programme and budget for appropriate
                  infrastructural support, such as modification of
                  buildings and storage facilities; and

      54.2.8.     Appropriate managerial training, monitoring and
                  evaluation of the programme.

I do not say that all of these things can be done instantly throughout
our country. They plainly can not. But if our country is going to deal
with the HIV/AIDS crisis, we have to get on with planning and
implementing a comprehensive programme of this kind without
further delay. What distresses me most, as a clinician who deals

every day with the consequences of this epidemic, is that we still do
not even have a decision to plan and implement such a programme,
let alone the programme itself. This is leading and will continue to
lead to avoidable human suffering and death, on a vast scale.


55.   In my professional opinion antiretroviral therapy, such as
  Nevirapine or AZT, for use in the prevention of mother-to-child
  transmission of HIV, significantly reduces the risk of HIV
  transmission from mother to child; nothing which has been said on
  behalf of the Respondents have changed my opinion.

56.   The provision of Nevirapine is safe for both mother and infant;
  and it is a critical public health care measure that enhances the
  choices of all women of reproductive age.

57.   The use of Nevirapine for this indication is simple, cheap and
  consistent with the latest recommendations of international health

58.   To prevent mother-to-child transmission of HIV, the a package
  that includes voluntary counseling and testing, antiretroviral
  therapy such as Nevirapine, and the option of using formula milk is
  an essential public health measure.