HIV and AIDS Research in South Africa Prof Anthony D MBewu BA MBBS FRCP MD FMASSAf

President The Medical Research Council

Presentation to the Parliamentary Portfolio Committee on Science and Technology

29 August, 2006 http://www.mrc.ac.za

Mandate of the MRCMRC Mandate

Statutory Council - 37 years old, Act 58 of 1991

‘the objects of the MRC are, through research, development and technology transfer, to promote the improvement of the health and quality of life of the population of the Republic, and to perform such functions as may be assigned to the MRC by or under this Act’.

MRC Vision :

‘building a healthy nation through research’

MRC Mission : ‘to improve the nation’s health and quality of life through promoting and conducting relevant and responsive health research’

Figure 1 : Prevalence of HIV among antenatal clinic care attendees in South Africa, 1990-2005

0.71.7 2.2

4

7.6

10.4

14.2

17

22.8 22.4

24.5 24.826.5

27.929.5

0

5

10

15

20

25

30

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Year

HIV

Pre

vale

nce

(%

)

HIV prevalence levels by sex and

age group in 2005

0%

5%

10%

15%

20%

25%

30%

35%

0-4

5-9

10-1

4

15-1

9

20-2

4

25-2

9

30-3

4

35-3

9

40-4

4

45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80-8

4

85+

Age group

Per

cen

tag

e

Males

Females

Cause Deaths Percentage1. Tuberculosis

2. Influenza and pneumonia

3. Ill defined and unknown causes

4. Violence and trauma

5. Other forms of heart disease

6. Events of undetermined intent

7. Stroke

8. Hypertensive diseases

9. Diarrhoeal diseases

10. Immune mechanisms

11. General Symptoms and Signs

12. Chronic lower respiratory disease

13. Resp and cardiac in perinatal period

15. Diabetes mellitus

16. Other diseases of the respiratory system

17. Ischaemic Heart Disease

22. HIV disease

TOTAL

77 406

72 663

58 333

52 491

49 472

38 691

35 927

31 558

27 364

26 517

24 954

20 883

19 220

18 524

18 000

17 513

11 926

567 488

13.6

12.8

10.3

9.2

6.8

6.8

6.3

5.6

4.8

4.7

4.4

3.7

3.4

3.3

3.2

3.1

2.1

100

Causes of Death in 2004 in South Africa

Statistics South Africa 2005

Cause Deaths PercentageHIV/AIDS

Ischaemic heart disease

Homicide/violence

Stroke

Tuberculosis

Lower respiratory infections

Road traffic accidents

Diarrhoeal diseases

Hypertensive heart disease

Diabetes mellitus

165 859

32 919

32 485

32 114

29 553

22 097

18 446

15 910

14 233

13 157

29.8%

5.9%

5.8%

5.8%

5.3%

4.0%

3.3%

2.9%

2.6%

2.4%

Top 10 causes of death, South Africa 2000 National Burden of Disease Study, Total deaths 556 585

Source: Bradshaw et al., 2003

HIV PREVENTIONHIV PREVENTION Behavioural – ABC (Abstinence, Be faithful,

Condomise)

Other technologiesBarrier Methods

Male and Female Condoms

Vaginal Diaphragms

Vaginal Microbicides

Male Circumcision

Other Prevention

Technologies

Vaccines

PREP

Management of STIsARV for Prevention

Objectives of the MRC HIV and AIDS Research Lead Programme

• Coordination of MRC HIV AIDS research : 80 researchers in 10 research units; R 160 million p.a.

• ensure correct prioritisation of research

• avoid unnecessary duplication of research efforts

• guide strategic fit of international research collaborations

• facilitate translation of research results into policy

• Behavioural Interventions• Epidemiological Studies• Clinical • Health Systems; Poverty; Intersectoral Interventions• Prevention of Mother to Child Transmission• Natural products and nutrition for immunemodulation• Vaccine development : SAAVI• Prevention technologies : vaginal microbicides• Bioinformatics and telehealth education• Novel Therapies : Biotechnology• Human development and Community Involvement • Evidence-based Medicine• Research Translation

Subthemes of the MRC HIV and AIDS Research Lead Programme

1. Behavioural Intervention

Sexually-related behaviours that result in exposure to the HIV virus are the main fuel forthe epidemic in Africa : - unprotected sexual intercourse - multiple sexual partners - sexual intercourse during bouts of STI - late healthcare seeking behaviour

These sexual behaviours are moulded by :• psychosocial determinants - such as self efficacy • environmental determinants - such as condom disposal• social determinants – such as the power relations between men and women and• economic determinants – such as poverty

Consequently, any effective and sustainable programme of interventions to halt theHIV and AIDS epidemic is bound to be centred upon behavioural change

With widespread awareness of AIDS, young South Africans seem to be taking steps tolimit their exposure to the HIV (SADHS 1997; YRBS 2002; RHRU 2002; Antenatal ClinicSurvey 2005)

2.2. Epidemiological StudiesEpidemiological Studies

• Antenatal Clinic Survey 2005 : 5.54 million estimated to be HIV

positive (11.6%) in population of 47 866 984

• ASSA 2000 estimate 599 298 need treatment for AIDS according to SA

guidelines – 225 775 already on treatment (37%)

• ASSA 2000 model : estimate 354 379 AIDS-related deaths in 2006

• Incidence (new infection rate) seems to be declining (521 607 in 2006,

2% reduction over 2005 : ASSA) ; whilst deaths increasing

• Life expectancy at birth was falling (50.7 in 2006) but may have increased

in past year due to 220 000 on treatment (Stats SA)

3. Clinical Research

Antiretroviral therapy• Patients on comprehensive treatment including ARVs in Africa live for years with reduced

episodes of opportunistic infection• South Africa has the largest Comprehensive Treatment Plan in the world with hundreds of

thousands screened; and over 138 336 on treatment (total 220 000 on treatment of estimated 599 298 requiring treatment - ASSA). In 231 public health facilities. MRC chaired the Taskteam

that wrote the Plan. • Monitoring and evaluation : quality of life, lifespan, side-effects • Treatment during acute infection? SPARTAC• Initiating antituberculous therapy?• Interaction with traditional medicines? • Fixed Dose Combinations• New therapeutic agents

Cotrimoxazole• 30% reduction in death; 34% reduction in hospital admissions

Multivitamins• 29% reduction in progression to Stage IV or death

Traditional Medicines• Efficacy• Safety • Interactions with ARVs

Opportunistic Infections

4. Health Systems; Poverty; and Intersectoral Interventions

In South Africa, infant mortality of 45.4 per 1000 relates to diseasessuch as gastroenteritis, respiratory infection – many of these being HIVpositive infants - “Good Start” – PMCT Cohort and Infant Feeding “Good Start” – PMCT Cohort and Infant Feeding

Study Study

‘To prevent most of these unnecessary deaths could cost over R5 billion annually in terms of investment in housing, education, cleanwater, health clinics, healthworker training, nutritional supplements etc’(MBewu et al 2000)

Impact of AIDS on the economy : reduction of GDP growth by 0.4% in 2010 ? (Bureau for Economic Research, Univ of Stellenbosch)

5. Prevention of maternal-to-child transmission of HIV

• The chances of an HIV positive mother transmitting the virus to the child during vaginal delivery is 21 - 43%

• Nevirapine monotherapy reduces vertical transmission by 48% (95% CI 17% to 60%)

6. Natural Products and Nutrition for Immunemodulation

• 80% of South Africans use Traditional Medicines

• MRC animal toxicity studies; Phase I studies

• Fawzi NEJM 2003 : multivitamins - 29% reduction in

progression to Stage IV or death

• Comprehensive Plan includes nutritional supplementation

and multivitamins for both those with AIDS and those who

are HIV positive

7. South African AIDS Vaccine Initiative

Expected Outputs

• effective, affordable locally relevant HIV vaccine

• scientists plus the infrastructure of a sustainable vaccine biotechnology industry in South Africa.

The most impressive HIV vaccine development programme in the developing world

Progress

• Completed two Phase I clinical trials• Phase I trial with South African designed vaccine in 2006• Phase II trial later this year• Phase III clinical trails within the next few years

8.8. Prevention Technologies : Prevention Technologies : Microbicides, CircumcisionMicrobicides, Circumcision

• High number of HIV infections among women worldwide

• Need for technologies to prevent sexual transmission of HIV

• Male condoms – women not able to negotiate use with male partners

• A women-controlled method applied before sex that could kill, neutralize, or block HIV and other sexually transmitted infections Female condoms – costly and require a certain level of skill and acceptance by male partners

• Circumcision : ?60% reduction in HIV transmission

0 1,000

kilometers

2,000

Produced by: The Health GIS Scentre, MRC, Durban, 2002Source: Africa Data Sampler

South Africa as part of Africa

South Africa

Zimbabwe

Malawi

UgandaKenya

Cameroon

Benin

Nigeria

Tanzania

Zambia

Burkina Faso

CARRAGUARD

CELLULOSE SULFATE

2% & 0.5% PRO2000

BUFFERGEL & 0.5% PRO2000

C31G (SAVVY)

India

Philadelphia, USA

PHASE IIB/III MICROBICIDE PHASE IIB/III MICROBICIDE TRIALS: GLOBALLYTRIALS: GLOBALLY

Ghana

0 200

kilometers

400

Produced by: The Health GIS Scentre, MRC, Durban, 2002Source: Statistics South Africa

KwaZulu-Natal Province as part of South Africa

Durban

Mtubatuba

Hlabisa

JohannesburgPretoria

Cape Town

Johannesburg: RHRU

Pretoria: MEDUNSA

Cape Town: UCT

Mtubatuba: Africa Centre

Durban/Hlabisa: MRC

Durban/Vulindlela: CAPRISA

PHASE IIB/III MICROBICIDE TRIALS: PHASE IIB/III MICROBICIDE TRIALS: SOUTH AFRICASOUTH AFRICA

CARRAGUARD

CELLULOSE SULFATE

2% & 0.5% PRO2000

BUFFERGEL & 0.5% PRO2000

9. Novel Therapies : Biotechnology

• Fusion inhibitors – NCEs, natural products

• ‘Bystander effect’

• Immunemodulators : African Traditional Medicines

• Adjunctive therapies

10. Human development and Community Involvement

People/Organizations – directly/indirectly affected and participating in the research process e.g:

• Individual/Partners/Family• Community Structures (NGOs/CBOs)• Service Providers• Stakeholders/Government Officials

11.11. Evidence-based MedicineEvidence-based Medicine

• Treatment & prevention of oral candidiasis in HIV-infected adults & children

• Balanced diet to reduce morbidity & mortality in HIV-infected adults

• Micro-nutrient supplementation to reduce morbidity & mortality in HIV-infected

children and adults

• Male circumcision for preventing transmission of HIV in heterosexual men

• Behavioural interventions for reducing HIV risk and infection in employees in

occupational settings

• Cotrimoxazole for prophylaxis of opportunistic infections in adults and children

• Stavudine, Lamivudine & Nevirapine for reducing morbidity and mortality in HIV-

infected adults

Successful Prevention Strategy

Enhanced by synergistic use of social, behavioural, biomedical and barrier methods

BARRIER METHODS

TREATMENT/ ARV/STI/

ANTIVIRAL

MICROBICIDES & VACCINES

MALE CIRCUMCISION

BEHAVIOURAL MODIFICATION

Lead

ers

hip

& s

calin

g u

p o

f tr

eatm

en

t/p

reven

tion

eff

ort

sC

om

mu

nity

involv

em

en

t

CONCLUSIONCONCLUSION