An update on HIV prevention and treatment

Prof Francois VenterWits Reproductive Health and HIV Institute (WRHI)

University of the WitwatersrandOct 2012

AIDS in Africa

Tensions…

• Prevention versus HIV treatment• HIV versus other illnesses• Public health versus human rights versus

the law• Government versus donor responsibility

Who is at fault?

• Politicians and voters• Public Health experts • Clinicians• Researchers• Donors

Kenya, 245,162

16%Mozambique,

156,10810%

Tanzania, 139,151

9%

Uganda, 78,769, 5%

Eritrea4,838 Madagascar

1,491Mauritius

584Comoros

28

South Africa, 473,499

31%

Zambia, 103,077

7%

Ethiopia, 94,489

6%

Malawi, 86,905, 6%

Rwanda, 9,225, 1%

Botswana, 13,518, 1%

Swaziland, 15,131, 1%

Namibia, 16,082, 1%

Angola, 21,777, 1%

Lesotho, 22,666, 1%

Zimbabwe, 45,652, 3%

Eastern & Southern Africa

1.5 million (57%

Rest of the world1.2 million (43%)

Global new infections, 2.7 million ESA new infections,

Prov. estimate 1.5m

Estimates of New Infections in Eastern and Southern Africa, 2007

0

150

300

450

600

2000 2005 2010 2015

South AfricaBrazilNamibiaChile

Measurement of Generally Accepted Indicators Reveals that the South African Healthcare System is Functioning Poorly by International Standards

16

13

31

260

300

250

230

540

6

8

16

110

210

230

300

400

450

1,9001,800Afghanistan

India

South Africa

Iraq

China

Namibia

Brazil

Chile

United Kingdom

Netherlands20002005

Note: MMR = Number of Maternal deaths per 100,000 *Public Sector deliveries estimated. Live births is used as a proxy for the number of pregnancies annually.MMR is an indicator of the quality of a health care system Source: WHO Maternal Mortality Report, 2007, StatsSA

Maternal Mortality Rates by Geography (2000 vs 2005)

MDG 2015 Target

Trend Projection for Maternal Mortality Rate until 2015

58

2

Since the SA ARV rollout started…

• 2 million people on treatment (& million worldwide)

• 5 million deaths• 5 million new infections

Implications

• HCT campaign 1st April 2010….• 15 million tests, linked to TB, other chronic

illness screening

New guidelines

CD4

Gets HIV!

Needs ARV’s

8 to 10 years

What happens if you get HIV?

Wellness – nutrition, exercise, stop smoking, safe sex, mental health, ↓ alcohol

How good are the antiretrovirals?

Before and after initiation of ARV therapy!

Thapelo

Before and after initiation of ARV therapy!Before and after initiation of ARV therapy!

ART outcomes - good news• National programmes

reporting good outcomes

• 1 year survival estimated as 93-95%

• 2 year survival 91%

• SA life expectancy up

How long will people live for?• ? 20 years or more on the

treatment package !! – CROI 2005

• Danish study – 39 years!• American – lose 12 years• French – NORMAL after

6 years• Uganda – normal!• Geriatrics, fertility

In summary, what has changed:• CD4 350, for all• Initiation of infants immediately• New maternal health/ PMTCT• New 1st line drugs for adults, kids• Altered second line• Expedited referral with timelines• Decreased monitoring• TB• Nurse initiation focus

Therapy for Early HIV Infection

200

500< 200

350CD4 Count (cell/mm3)

Symptomatic

(Stages 3 & 4)Asymptomatic

(Stages 1 & 2)

Clinical Symptoms

164187

102

181

200192

87 239

163

97

134

179

97100125

12386

122103 53

157 20695

72

Review of data from 2003-2005 from 176 sites in 42 countries (N = 33,008)

When Is Antiretroviral Therapy Started?

Egger M, et al. CROI 2007. Abstract 62.

Children

• All children less than 1 year of age

• Children 1 – 5 years with clinical stage 3 or 4 or CD4 ≤ 25 % or absolute CD4 count < 750 cells/µl

• Children ≥ 6 years to 15yrs with clinical stage

3 or 4 or CD4 < 350 cells/µl. Huge implications for PCR screening!

MDR and XDR?

Treatment as prevention

• Prevention programmes results very disappointing

• Can reducing the viral load earlier have a public health impact?

• Convenient convergence!

• Essentially, treatment IS prevention

1st line adults

• All new patients needing treatment, including pregnant women

- TDF + 3TC/FTC +EFV/NVP • Contraindication to TDF: renal disease

AZT+ 3TC +EFV/NVP• For those on existing d4T, remain, but

vigilance urged

ddI

d4T

AZT

3TC

2 Nukes Non-nuke

Efavirenz/ nevirapine

Protease

Kaletra

Failure – VL>5000Toxic!

Who is still taking d4T?

28.4

78.6

47.6

77.8

45.8

62.7

7.3

24.0

4.7

8.98.6

25.9

5.26.1

11.2

3.5

11.10

6.01.8 1.3

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

Cote d'Ivoire Mozambique South Africa Tanzania Zambia

d4T-3TC-NVP d4T-3TC-EFV d4T-FTC-EFVd4T-FTC-NVPAZT-3TC-NVPAZT-3TC-EFVTDF-FTC-EFVTDF-FTC-NVPd4T-3TC-LPV/rOther

1.30.14.6

0.0020.1 0.22.1

9.1

4.6

0.1

Marlink R et al , IAC 2008 (WEAXO106)

Westreich DJ, et al, Tuberculosis treatment and risk of stavudine substitution in first-line antiretroviral therapy, Clin Infect Dis. 2009 Jun 1;48(11):1617-23

Side effects potentiated by TB Rx

Major issue: PMTCT

• Complex regimens – being updated

What can stop us?

• Human resources• Budget and treasury• Beaurocracy and legislation

Context of care

Challenges

The difference?What we want• INH• CTX• Regular monitoring• Pap smears, fertility

planning • ‘Wellness’ – ‘prevention

for positives’• (no weekend work,

patient in clinic when suits us, keep their appointments)

What patients want• Being valued• No queues• Same health care worker• Tablets that work• Confidentiality• Files and blood tests that

don’t go missing• Information that is

appropriate• Grants!• Appointments, hours that

don’t impact on work

• The biggest challenge to our programmes is NOT safe or effective drugs or HIV testing – it is retention in care after HIV diagnosis

1st prize is a bulletproof 1st line ARV regimen

• Tolerability > forgiveness (NNRTI vs PI)• BUT – presupposes good support and

adherence• 2-3% migration to 2nd line – accumulating

body of patients• Long haul – probably 50% of patients

need minimal support

FDCs

• More for pharmacists than patients!• Packaging and colours would be great

Issues around paediatrics

• The least “system proofed” group• Try to harmonise with adults• Weight of liquid formulations – score

tablets, pay attention to ‘crushability’

OI drug needs

• Amphotericin B• Macrolides - MAC• Gancyclovir – CMV, possibly for other

illnesses• MDR treatment • (Rifabutin)

PoC technologies?

• Proliferation of technologies with parallel lab system - ?justified in an HIV silo ?toxicity monitoring required

• Gene Xpert• Viral load• ?CD, ?Resistance• ?POC rapid HIV test re-evaluation• Sober reflection on the tech requirements

Summary of big ‘short term’ treatment and systems gaps?

• Earlier diagnosis and retention • Bigger emphasis on more sophisticated adherence,

esp toxicity management – preserve 1st line• Better packaging of drugs, FDCs• New drugs for toxicity • OI drugs• Better and faster diagnosis of TB, VL; Reassess rapid

HIV• Simpler guidelines, align paeds and adult guidelines• Expansion of who gives ART

HIV has showed what we can do

• Opportunity to fix the whole health care system now

• Heed our marching orders for 2012!

The End