AFFIDAVIT

I, the undersigned

ROBIN WOOD

do hereby make oath and state as follows:

1.	The facts deposed to in this affidavit are 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. 

2.	In 1986, I registered with the then South African Medical and Dental Council (now the Health Professions Council) as a medical practitioner and again during 1990 as a Specialist of Internal Medicine. My registration number is MP 282162 

3.	Between 1967 and 1990, I obtained the following degrees and diplomas: Bachelor of Science in Biophysics (1st Class Hons), London University; Bachelor of Medicine and Bachelor of Surgery, Oxford University; Masters in Medicine, University of Cape Town; Diploma of Tropical Medicine & Hygiene, Liverpool University; Diploma of Royal College of Obstetrics and Gynaecology, London and I am a Fellow of the College of Physicians (SA).  In addition, I spent two years (1990-1992) at Stanford University Medical School, CA. USA engaged in an “Infectious Diseases Fellowship”.  

4.	Currently, I hold the position of Principal Medical Specialist for the Provincial Administration of the Western Cape.  I also hold the following additional positions: I am an Associate Professor of Medicine, University of Cape Town; the Head of Department of Medicine, Somerset Hospital and the Director of HIV Research Unit, at Somerset Hospital. In addition, I was also the Director of the Infectious Diseases Research Unit at the UCT Lung Institute.      

5.	Since 1993, I have developed extensive and specialist HIV/AIDS-related research and clinical experience in South Africa.  I have been involved as the principal investigator for 25 HIV-related studies.   I have researched and co-authored more than 57 peer-reviewed articles and I have presented more than 80 abstracts at national and international science conferences on HIV/AIDS treatments.  I have served and continue to serve on local, provincial, national and international committees on treatment for HIV/AIDS and other infectious diseases.  (Annexure:RW1 CV – Robin Wood)

6.	I respectfully submit that I am by training and experience, duly qualified to express the views and opinions that I shall express in this affidavit and to assess the repute, opinions and reliability of other experts that I may refer to.  

7.	Based on scientific evidence, clinical trials and international consensus, this affidavit will conclusively demonstrate that prevention of mother-to-child HIV transmission should be part of the minimum standard package of care for women who are known to be HIV infected.  This will also enhance the choices available to all women of reproductive age. Further, it will show that the use of Nevirapine, an antiretroviral drug registered in South Africa for this indication is simple, cheap and consistent with the latest recommendations of international health authorities.

INTRODUCTION
8.	HIV/AIDS is a progressive disease of the immune system that is caused by the Human Immunodefiency Virus (HIV). When left untreated, HIV profoundly depletes the immune system and may prove fatal because of the inability of the body to fight opportunistic infections such as tuberculosis, pneumonia and meningitis. (Annexure: RW2 Durban Declaration)   

9.	A recent Ugandan study shows that the majority of people with HIV/AIDS in Africa have a median survival rate from HIV seroconversion to an AIDS-related death that ranges from 8.3 to 12.1 years. This is comparable with survival rates in Europe and North America prior to the introduction of combination ARV therapy.  Evidence indicates that without antiretroviral therapy, the majority of people with HIV/AIDS die prematurely of illnesses that destroy their immune systems, quality of life and dignity.  Early diagnosis, clinical management, medical treatment of opportunistic infections and the appropriate use of anti-retroviral therapy prolongs and improves the quality of life of people with HIV/AIDS. In its HIV/AIDS Policy Guideline the Department of Health recognises the efficacy of anti-retroviral treatment: “Current research strongly indicates that suppressing HIV viral activity and replication with anti-retroviral therapy combinations prolongs life and prevents opportunistic infections.” (Annexure: RW3 – Guidelines on the management of opportunistic infections)

MOTHER-TO-CHILD-TRANSMISSION AND PREVENTION
10.	The Human Immunodefiency Virus (HIV) is transmitted in four basic ways – through unprotected sexual intercourse, infected blood and blood products, from a pregnant woman-to-child, and from breastfeeding from an infected mother.  HIV transmission from an infected mother to her infant is the subject of this affidavit.  The annual HIV sero-prevalence study at clinics across the country in October 2000 demonstrates that approximately 24.5% (1999 = 22.4%) of women attending antenatal clinics in the public health services in South Africa had HIV. Information from this survey projects that there are approximately 4.68 million (1999 = 4.2 million) people in South Africa living with HIV/AIDS. (Annexure: RW4  Ante-Natal Surveys 1999 and 2000)

11.	Approximately one third of women with HIV will transmit the virus to their offspring.  In South Africa, it is estimated that more than 60 000 new infections each year are as a result of mother-to-child transmission of HIV.  This is the most common way that HIV is transmitted to children (Annexure: RW5 AIDS Bulletin March/April 1999)  

12.	In 1994, the findings of the Paediatric AIDS Clinical Trials Group (PACTG) trial PACTG076 were published.  These findings established beyond doubt that the provision of AZT (zidovudine) after the first fourteen weeks in pregnancy significantly reduced the rate of mother-to-child HIV transmission.  (Annexure:RW6 PACTG076)  This gave hope to women with HIV/AIDS, health professionals and governments.  PACTG076 has become the standard of care in many developed countries.  However, the cost of the drug at 100mg five times daily is exorbitant and beyond the reach of the vast majority of people in the developing countries. 

13.	On 19 February 1998, the results of the Bangkok Perinatal AZT Study (also known as the Thai Study) that tested the safety and efficacy of short-course AZT therapy were announced.  The Thai Study reduced mother-to-child HIV transmission by 50% and used only 300mg twice daily from the 36th week of pregnancy and 300mg every two hours during labour.  This study offered hope to people in developing countries because the shorter course AZT was much cheaper and could be incorporated into the prevention programmes of these countries.  Thailand introduced a country-wide mother-to-child HIV prevention programme in 1999.  According to the WHO, Thailand has halved HIV infection in newborn children and that country is providing technical assistance to other countries in the Mekong Region. (Annexure: RW7 Thai Study)  

14.	Whilst the Thai Study indicated that AZT reduces the rate of vertical transmission of HIV in non-breastfed populations, studies in Côte d’Ivoire and Burkina Faso showed significant reductions in breastfeeding populations. Results published in March 1999 indicated that short course AZT given before birth was well accepted and tolerated and provided a 38 percent reduction in vertical transmission despite breastfeeding. (Annexure: RW8 Côte d’Ivoire Study) 

15.	In South Africa, at Khayelitsha in the Western Cape, significant reductions of approximately 50% in mother-to-child HIV transmission have been recorded using the short-course zidovudine programme in an operational context since January 1999.  The programme illustrates the feasibility and public health benefit of a mother-to-child HIV prevention programme using a fairly complex anti-retroviral regimen. (Annexure: RW9 SAMJ)

16.	Prevention of mother-to-child HIV transmission was further assisted with studies on the drug Nevirapine in 1999, which is cheaper and easier to use.

NEVIRAPINE AND PREVENTION OF MOTHER-TO-CHILD-TRANSMISSION
17.	Nevirapine is an antiretroviral drug that is used to treat HIV/AIDS and more recently to reduce HIV transmission rates from mother-to-child.  The drug is registered by the South African Medicines Control Council (MCC) to treat HIV in adults, adolescents and children with HIV/AIDS and more recently for the prevention of mother-to-child-transmission of HIV. (Annexure: RW10 MCC)

18.	Nevirapine belongs to a class of anti-HIV drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although NNRTIs use a different mechanism to stop HIV from replicating compared to the nucleoside analogue reverse transcriptase inhibitor (NARTI) drugs such as abacavir, zidovudine (AZT), didanosine (ddI), stavudine (d4T) and lamivudine (3TC), both classes of drugs target the same step in the virus' reproduction cycle.

19.	Nevirapine is a fast-acting and potent antiretroviral with a long half-life, i.e. it takes long to be eliminated from the body. Accordingly it was deemed to be a valuable option to reduce the risk of mother-to-child transmission of HIV, since it was absorbed quickly in the body, passed readily through the placenta, a limited dose was needed and it would remain active in the body of both mother and infant for a period which could limit HIV infection.  

Safety of Nevirapine
20.	Various studies were accordingly performed to test the safety of Nevirapine for use in the prevention of mother-to-child transmission of HIV.

21.	The ACTG 250 study performed in seven hospitals in USA and Puerto Rico had as its aim to define the dosage regimen that maintains a serum concentration of Nevirapine above 100ng/mL through the first week of the life of the infant. The dosing schedule arrived at was a single maternal dose during labour followed by a single dose to the infant between 48-72 hours after birth. No toxicity was noted in infants or their mothers. (Annexure: RW11 ACTG 250)

22.	The HIVNET 006 trial conducted in Uganda compared also tested safety of Nevirapine in women who received a single 200mg dose of Nevirapine during labour. Half of the infants received a single dose of Nevirapine (2mg/Kg) 72 hours after birth, and half did not receive Nevirapine. Drug levels in breast milk remained low in most mothers throughout the first week after delivery. No serious adverse events related to Nevirapine was observed. (Annexure: RW12 HIVNET 006)  

23.	After ten years of use, there have been reports of serious adverse effects including reports of five deaths in women in Europe, the US and South Africa who have used Nevirapine on a daily basis as chronic medication together with other antiretrovirals.  The European Medicines Evaluation Agency issued a public statement in April 2000 drawing attention to the risk of liver disease from the use of Nevirapine. These adverse effects have always related to a very small percentage of people who use the medication as treatment not as a once-off dose to prevent mother-to-child transmission. (RW13 Treatment Issues January 2001)

24.	I submit that there is no doubt as to the safety of Nevirapine for use in the prevention of mother-to-child transmission of HIV.

Efficacy of Nevirapine
25.	These positive results of pharmacokinetic and safety studies of Nevirapine have prompted more larger clinical trials to evaluate the efficacy of Nevirapine for mother-to-child transmission prevention.

26.	The HIVNET 012 study is a randomized controlled trial conducted in Uganda which compared the use of a maternal single 200mg oral dose of Nevirapine during labour and an infant 2mg/kg dose of Nevirapine within 72 hours of birth, with a maternal 600mg oral dose of AZT at onset of labour and 300mg orally every 3 hours during labour, with an infant 4mg/kg twice daily dose of AZT for 7 days after birth.  This study was conducted in a breastfeeding population. At 6-8 weeks of age 11,9% of infants in the Nevirapine group were HIV infected, compared with 21,3% in the AZT group, similarly at 14-16 weeks of age, 13% of infants in the Nevirapine group were infected, compared with 25% of infants in the AZT group. At 14 weeks of age 95% of all infants were still breastfeeding. Data from 618 women and infants were looked at. HIVNET 012 researchers cite as advantages of Nevirapine, its simplicity, low cost and potential for widespread use. Compared with other antiretroviral treatment it achieves a similar reduction of transmission in a single dose. Mother-infant pairs continue to confirm that Nevirapine was safe and significantly reduced the mother-to-child transmission rate compared to AZT. (Annexure: RW14 HIVNET 012) The PETRA study on the efficacy of short-course AZT in combination with lamivudine (3TC) demonstrated a reduction in mother-to-child transmission of between 52% and 37% depending on the dosage and combination used. In comparison, the HIVNET 012 trial demonstrated a 47% reduction in mother-to-child transmission of HIV with the use of Nevirapine.

27.	Subsequent to the publication of the HIVNET 012 results, the World Health Organisation included Nevirapine for mother-to-child transmission prevention on its Essential Drug List in December 1999. (Annexure: RW15 EDL2000)

28.	1306 HIV-infected women participated in the South African Intrapartum Nevirapine Trial (SAINT) and were assigned to 2 arms comparing 200mg of Nevirapine during labour and 1 dose to mother and infant 24-48 hours after delivery, to multiple doses of AZT and 3TC during labour and for 1 week after delivery to mother and infant. No significant differences was observed between the two arms and both regimes were viewed as effective and comparable to the results of Nevirapine in the HIVNET 012 trials and AZT and 3TC in the PETRA Arm B. Preliminary results were released in July 2000. (Annexure: RW16 SAINT)

Resistance to Nevirapine
29.	 The HIV virus mutates constantly and rapidly.  It is in the nature of the virus. As a consequence some variants containing anti-retroviral resistance mutations occur naturally (ie in the absence of drug pressure) at low frequency. These variants are rapidly selected in the presence of drug selection pressure.

30.	An early study found that 3 of 15 women receiving a single-dose of Nevirapine in the HIVNET 006 study had the K103N Nevirapine resistance mutation identified at 6 weeks postpartum.   

31.	 The apparently Nevirapine-induced mutations in mothers and babies were different, indicating that they arose de novo in mothers and infants and were not transmitted.  Studies in Uganda suggest that approximately 20% of mothers and 46% of infants develop mutations after one dose of Nevirapine. 

32.	The mutations cause no harm to the mother, except that they may make her resistant to treatment with that class of ARVs for as long as they remain there.  Treatment options for the mother may need to be tailored to avoid certain classes or combinations of drugs. Triple drug therapy would be expected to be effective even in the presence of Nevirapine mutations.
 
33.	The mutations are transient and disappear, after which it can be assumed   that that class of ARVs will again be effective.

34.	It is unknown if such a low level resistance would preclude use of Nevirapine in subsequent pregnancies.  Since the resistant virus loses its selective advantage within 2-3 months after the stopping of the drug and is no longer detectable in the affected individual, it may be susceptible to a second exposure to Nevirapine.  

35.	There is no evidence that the transient appearance of these mutations in the mother causes any public health risk.  It may not be transmitted at all, and in any event it is transient.

36.	Since the majority of women do not yet have access to antiretroviral treatment, the impact of resistance is small and is outweighed by the positive results Nevirapine has in preventing mother-to-child transmission of HIV.   There is no evidence that Nevirapine accelerates progression of the HIV disease or increases transmissibility.

ALTERNATIVE FEEDING, BREASTFEEDING AND INFORMED CHOICE
37.	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.

38.	 Breastfeeding accounts for 15-44 percent of mother-to-child transmission of HIV, depending on the duration of breastfeeding after birth. Factors that may increase transmission of HIV through breast milk include recent infection in the mother during either pregnancy or the breast feeding period (this is itself a period that is associated with higher maternal viral load), poor breastfeeding techniques (which may result in fissured nipples), and damage to the child’s mucous membranes (caused by infection, such as oral thrush, or intestinal damage due to allergic reactions to cow’s milk or complementary foods). 

39.	Breastfeeding remains one of the most effective strategies to improve chances of child survival. This is because breast milk provides for the infant’s fluid and nutritional requirements, as well as growth factors and antibacterial and antiviral agents that protect the infant from disease. In the poorest developing countries and communities where hygiene and sanitation are often poor and access to health care is limited, infant mortality is primarily due to infectious diseases such as diarrhea and pneumonia. Under such conditions, artificial feeding can put infants at increased risk.  

40.	The high cost and limited access to safe drinking water are factors in deciding whether to recommend formula feed to mothers. Counseling regarding the risks and benefits of available infant feeding methods and how to make the chosen method as safe as possible is the only way to resolve the dilemma until clean water is provided to poor communities.   Over the years the World Health Organisation advised that HIV positive women in resource-poor areas be encouraged to make an informed choice about infant feeding, weighing both its relative risks and its potential benefits. Women should therefore be supported in their choice to breast-feed/formula feed, where such a decision is made. 

41.	A studyof 401 mother-infant pairs in Kenya found that at 24 months, the cumulative probability of HIV-1 infection was 36.7% in the breastfeeding and 20.5% in the formula arm. Among the 16% more infections in the breastfeeding arm, almost half was attributable to breastfeeding. At 2 years of age the HIV-1 free survival rates were significantly lower in the breastfeeding arm than the formula arm. The avoidance of breast milk was estimated to reduce MTCT by 44%.  

42.	Formula feed has been shown to be the most effective way to reduce the risk of mtct after child birth. The high cost of formula feed could be alleviated through bulk buying by the government and providing it for free to mothers who choose to breast-feed.  However, the choice must be that of the pregnant woman.  

43.	The use of antiretroviral drugs such as AZT or Nevirapine to reduce mother-to-child HIV transmission is beneficial even in an exclusive breastfeeding or mix-feeding population.

Policy recommendations of the World Health Organisation
44.	 In a recent UNAIDS/WHO report entitled “New Data on the Prevention of Mother to child transmission of HIV and their policy implications”, released in January 2001, a Technical Consultation comprising expert scientists and programme managers from various regions, HIV-infected mothers, representatives from NGOs implementing MTCT--prevention programmes and UN agencies, made conclusions and recommendations on the use of antiretrovirals. South Africa was represented at the consultation by its Chief Director of HIV/AIDS and STDs, Dr. Nono Simelela (Annexure: RW17 WHO Technical Consultation Report)

45.	On short-term efficacy of antiretroviral prophylactic regimens: They concluded that the simplest effective regimen includes single dose intrapartum/postpartum Nevirapine. The mechanisms by which these regimens provide protection against the mother-to-child HIV transmission include decrease of viral replication in the mother and/or prophylaxis of the infant during and after exposure to the virus. 

46.	On long-term efficacy of antiretroviral prophylactic regimens: They stated that the long-term efficacy of Nevirapine regimens has been demonstrated by infant status through 12 to 24 months, which shows that the early reduction in HIV transmission persists despite continued exposure to HIV during breastfeeding. 

47.	On safety of antiretroviral prophylactic regimens: They stated that the short-term safety and tolerance of the effective antiretroviral prophylactic regimens has been demonstrated in all the controlled clinical trials: The effective antiretroviral prophylaxis regimens have not been associated with an excess of severe adverse events (including mortality).  The WHO Technical Consultation concluded that the benefit of these drugs in reducing mother-to-child HIV transmission greatly outweighs any potential adverse effects of drug exposure.

48.	On selection of resistant viral populations: 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 resistance. 

49.	On breastfeeding and alternative feeding: The WHO Technical Consultation recommend that when alternative feeding is acceptable to the woman, feasible, affordable, sustainable and safe, avoidance of all breastfeeding by HIV-infected mothers is recommended. Otherwise, exclusive breastfeeding is recommended during the first months of life. This must be based on counselling the woman.
 
CONCLUSION
50.	I submit that antiretroviral therapy, such as Nevirapine, for use in the prevention of mother-to-child transmission of HIV, significantly reduces the risk of HIV transmission from mother to child; it 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.  The use of Nevirapine for this indication is simple, cheap and consistent with the latest recommendations of international health authorities. To prevent mother-to-child transmission of HIV, the following minimum care package includes voluntary counseling and testing, antiretroviral therapy such as Nevirapine, and the option of using formula milk. 

______________________________
DEPONENT

I CERTIFY THAT THE DEPONENT HAS ACKNOWLEDGED THAT HE KNOWS AND UNDERSTANDS THE CONTENTS OF THIS AFFIDAVIT WHICH WAS SIGNED AND SWORN TO BEFORE ME AT CAPE TOWN ON THIS ----- DAY OF AGUST 2001 AND THAT HE HAS NO OBJECTION TO TAKING THE PRESCRIBED OATH AND CONSIDERS SAME TO BE BINDING ON HIS CONSCIENCE.

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COMMISSIONER OF OATHS