10.00 DiGibb RCOG 27Nov2015 · The Conduct of Placebo-Controlled Trials Raised New Controversies Despite controversy, several critical placebo-controlled trials of shorter AZT regimens

HIV in the Next Generation:

the Rocky Road to Elimination

(focus on Africa)

Medical Research Council Clinical Trials Unit at University College London

Di Gibb

[email protected]

REALITY

Outline

• Millennium Development Goals

• Prevention of Mother-To-Child Transmission (pMTCT)

• Where have we come from?

• Strategies for pMTCT– From Option A to Option B plus

• Paediatric diagnosis & linkage to care• Where are all the children?

• Prevention of HIV in adolescents

Where are We in 2015?

Millennium

Development

Goals 4, 5 & 6

Integration of MDGs*

Reduce HIV/AIDS

Increase Child Survival

*Double Dividend:

An initiative between UNICEF, WHO and ElGPAF, launched 2013.

Sources: 1. UNAIDS. The gap report 2014

2. Prendergast A et al. Arch Dis Child 2015

3. Chopra M et al. Arch Dis Child 2015

Where are We in 2015?

eMTCT

(Virtual) Elimination

of Mother to Child

Transmission

Millennium

Development

Goals 4, 5 & 6

Integration of MDGs*

Reduce HIV/AIDS

Increase Child Survival

� MTCT <5% in

breastfed infants

� <40,000 new

infections/year

(UNAIDS Global Plan

2011-2015)

*Double Dividend:

An initiative between UNICEF, WHO and ElGPAF, launched 2013.

Sources: 1. UNAIDS. The gap report 2014

2. Prendergast A et al. Arch Dis Child 2015

3. Chopra M et al. Arch Dis Child 2015

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0

100,000

200,000

300,000

400,000

500,000

600,000

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

PM

TC

T c

overa

ge

New

HIV

in

fecti

on

s (

#)

Trends in new HIV infections among children (aged 0-14) and coverage of maternal ARVs form PMTCT in all

low- and middle-income countries, 2001-2012Maternal ARVs for PMTCT

New HIV infections in children (0-4)

Source: UNAIDS 2013 HIV and AIDS estimates, 2014, and UNAIDS/WHO/UNICEF Global AIDS Response Progress Reporting (GARPR)/Universal Access

Elimination (virtual) of Paediatric HIV:

Sources: 1. UNAIDS. 2013 HIV and AIDS estimates, 2014

2. UNAIDS/WHO/UNICEF. Global AIDS Response Progress Report /Universal Access data, 2006-14

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0

100,000

200,000

300,000

400,000

500,000

600,000

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

PM

TC

T c

overa

ge

New

HIV

in

fecti

on

s (

#)





In 2013:

*240,000 children acquired HIV

~660 new infections/day

*3.2 million children <15 years

living with HIV

91% in SubSaharan Africa


not there yet!



“Virtual elimination” of

MTCT in Europe

Jasseron et al 2011, von Linstow et al 2010, Naver et

al 2006, Chiappini et al 2011, Prieto et al 2012, ECS

unpublished data, Personal comm. Inga Latysheva

MTCT rates 2000-2011

� 33 infected infants among 5788

singleton live births

UK and Ireland

Country MTCT Time period

France 1.0% 2005-2009

Italy 1.0% 2005-2010

Denmark 0.5% 2000-2008

Sweden 0.6% 1999-2003

Spain 1.6% 2000-2007

Ukraine 4.1% 2008-2010

Russia 3-4% 2010

UK 0.57% 2007-2011

1987:

HIV Treatment Era Begins

� AZT (ZDV) approved by FDA in

March 1987 for treatment of adults

� Despite concerns about AZT toxicity, given high mortality of

paediatric AIDS, paediatric and obstetric researchers proposed

giving AZT to infected pregnant women to reduce MTCT.

“Treatment as Prevention”: PMTCT With AZT in 1991

� Giving a potentially toxic drug to

pregnant women and exposing their

fetuses was highly controversial.

� Before approving the 076 trial, the FDA held a

special public meeting to discuss the ethics of

giving AZT to pregnant women.

The AZT Regimen in PACTG 076 Was Designed to

Target Multiple Potential Time Points of Transmission

Pregnancy

AZT 100 mg

5 times daily

TARGET:

In Utero(after 1st trimester)

enrollment

CD4 >200

DSMB Stopped PACTG 076 Trial at

First Interim Efficacy Analysis in February 1994

Placebo 25.5%

Zidovudine 8.3%

First demonstration of treatment as prevention!

67% Reduction Transmission

Feb

1994

Dec

1994

076: Moving Rapidly from Evidence to Policy and

Implementation in Less than One Year

Feb 18

DSMB

stops

study Feb 21

First

press

report

March

NIH-

led

Public

Health

Service

Task

Force

set up

Jun 6

Public

hearing to

debate

guideline

s

Apr 29

Interim

guidance

for use of

AZT in

pregnant

women

Aug 4

PHS Task Force

issues expanded

recommendations

for use of AZT for

PMTCT

Aug 8

FDA

approves

new labeling

for AZT to

include

PMTCT

Dec 5

Medicaid

coverage

for AZT

PMTCT

required

in all

states

Nov 3

Results

In

NEJM

Translation of Trial Results into Practice – US

Global HIV Epidemic in Children

� After 1994, pMTCT implemented in resource-rich countries

& attention turned to the developing world, where most HIV-

infected children live.

� By 1994, an estimated 1 million HIV-infected infants born.

No. children 0-14 years living with HIV globally

World Health Organization Response to

PACTG 076 Results

� June 23-25 1994, WHO held a meeting of scientists & MOH to

discuss implications of 076 trial for the developing world.

� Concluded that best approach was to do randomized, placebo-

controlled trials of shorter and simpler regimens of AZT.

“ZDV regimen studied in ACTG 076 not applicable [high cost; operational

requirements] in parts of the world where most MTCT of HIV occurs,

placebo-controlled trials offer the best option for obtaining rapid and

scientifically valid results#no other effective alternative #.”

The Conduct of Placebo-Controlled Trials

Raised New Controversies

� Despite controversy, several critical placebo-controlled trials of

shorter AZT regimens developed for developing countries.

� Investigators collaborated and shared trial design, endpoints,

and conducted meta-analyses.

� Trials built sequentially on each other to enable evolving and

improving PMTCT standards for developing world.

1994 2015

Building the Evidence Road for PMTCT

BF

1994 US

PACTG 076: AZT

1999 Thailand

Bangkok CDC: Short

AZT 1999 Cote d’Ivoire

Wiktor CDC: Short

AZT 1999 Uganda

HIVNET 012: sd

NVP

2002 Cote d’Ivoire

DITRAME+: Short AZT +

sd NVP 2004 Thailand

PHPT-2: Short AZT + SD

NVP

2006 Botswana

MASHI: Infant

AZT 2008 Ethiopia, India, Uganda

SWEN: Infant NVP 6

wk 2008 Malawi

PEPI-Malawi: Infant NVP or

NVP/AZT 14 wk2009 Tanzania

MITRA-plus: Maternal ARV

6 mo2010 BotswanaMma Bana: Maternal

ARV 6 mo2010 Malawi

BAN: Infant NVP vs. Maternal

ART 6 mo

2014 Africa

HPTN 046: Infant NVP 6

mo

2000 Thailand

PHPT: Short vs Long

AZT

Modified from James McIntyre MD

2011 Africa

Kesho Bora: Maternal ART

6 mo

FF

2015 Africa

PROMISE: Maternal ART 2015 Africa

ANRS 12714: Infant 3TC or LPV/r 12 mos

CD4 < 350

PregnancyLabor &

DeliveryBreastfeeding

New

Pregnancy

Attend

Antenatal

care

HIV

test

CD4,

WHO

stage

CD4

result

STOP

Maternal triple ART prophylaxis STOP

Maternal lifelong ART (CD4 <350, WHO 3,4)

CD4 > 350

AZT Daily Infant NVPSD NVP and

AZT/3TC for 7 daysOption A

Option B

Re-

identify

at ANC

CD4,

WHO

stage

Re-

identify

at ANC

CD4,

WHO

stage

WHO Guidelines 2010: Option A or Option B

0

0.5

1

1.5

2

Transmission Risk by Study Arm

0.5%0.6%

Maternal ZDV

etc & infant

NVP – Option A

TDF/FTC +

LPV/RTV

1.8% Difference (CI)

-1.28% (-2.11 to -0.44)

ZDV/3TC+

LPV/RTV

Triple antiretroviral therapy is best for

reducing MTCT(Fowler MG, Abstract 31LB, CROI 2015)

Evolution of WHO PMTCT Guidelines Over Time - As New Evidence Becomes Available

Treatment No rec ART if

CD4 <200

ART if CD4

<200

ART if CD4

<350

ART if CD4

<500

PMTCT 4

weeks

AZT or

sdNVP

AZT from

28 wks +

sdNVP

AZT from

28 wks +

sdNVP +

AZT/3TC

7d “tail”

Option A

AZT/sdNVP +

infant NVP if BF

Option B

ART preg/BF

Option B

ART preg/BF

Option B+

Life-long ART

2001 2006 20102004 2013

Breakthrough:

prevention of

breastmilk MTCT

− Use of more

effective drugs

− Extend coverage

through BF

− ART for maternal

health

− Program

simplification

New guidelines recommend universal ART

for pregnant and breastfeeding women

IN 2015: ART should be initiated in all pregnant and breastfeeding

women living with HIV regardless of WHO clinical stage and at any

CD4 cell count and continued lifelong

Strong recommendation, moderate-quality evidence

• In 2010 we had Option A and B

• In 2013 Option A no longer recommended; instead Option B and B+

• Now lifelong ART for ALL people diagnosed with HIV Therefore, the

new guidelines do not speak of “options” but “universal ART”

• But the rationale behind this isn’t from PMTCT literature….

• Europe 33%, S. America 25%, Africa 21%, N. America 11%, Asia 10%

• Median age 36 years; 25% women

• Med CD4: 651 (range 503 to 2296) and Med VL: 12,000

• Patients randomized to early start or waiting till CD4 fall <350

• Trial was closed early by the DSMB because of higher than

expected benefit of ART

The START trial enrolled over 4000 people

with CD4>500 at 211 sites in 35 countries

Source: N Engl J Med 2015; 373:795-807

Overall there were 42 “events” in the immediate arm and 96 in the deferred arm p=<0.001

No difference in drug toxicities between arms and no evidence of harm caused by ART even

in clients with HIV CD4

When looking at the primary outcome of

death or severe disease, immediate ART was protective

July 2015

START

Strong recommendations for all

BHIVA 2015

US 2015

WHO 2015

EACS 2015

New ART initiations among pregnant and breastfeeding women, percentage of all new ART initiations

attributed to this population, Malawi 2008-2012 (CDC, MMWR 2013)

B Plus in Malawi – starting in 2011

In1st year of B+ implementation, the

number of pregnant and

breastfeeding women initiating ART

increased 748%

(CDC, MMWR 2013)

2004-2008, only 9% of

HIV+ pregnant women

started on ART (Braun et al, JAIDS, 2010)

BENEFITS HARMS

Prevent transmission in future pregnancies Additional risk of toxicity because of additional

time on ART

Reduced transmission to uninfected

partners

Programmes are seeing high rates of LTFU; may

have implications for resistance

Avoid stopping and restarting ART for future

pregnancies

Potential risk of loss in transition from MCH

delivered ART services to routine ART services

No need to establish eligibility prior to

initiating ART regimen

Increased net immediate cost (although maybe

cost effective in the long term)

Improved maternal mortality & slower

disease progression with continuous vs.

interrupted ART

Additional potential risk of resistance, especially if

women stop ART or are poorly compliant

Balance of Risks and Benefits for universal ART

No studies comparing Option B with B+

But…. there are data on stopping ART

• Postpartum women discontinuing ART experience CD4

decline; heterogeneity from studies:

• CD4 at BASELINE of <500, resulted in 6-20% of women

reaching treatment threshold within 6 months of stopping

(vs only 1.5% if CD4 >500)

• May present for next pregnancy with CD4 below threshold

for ART initiation (also suggested from UK data)

Policies adopted in 144 LMIC

80% - Option B+

For most countries, Universal ART for

pregnant women (B+) is already national policy

“…..reduction in the number of HIV-positive

children born by HIV positive mothers

from 6% to 2%, following the

introduction of the option B+ treatment”

New Vision, Uganda, January 28, 2015

0

100,000

200,000

300,000

400,000

500,000

600,000

2000 2014

Nu

mb

er o

f ch

ild

ren

Inception of Global

Plan13% decline between

2000 and 200848% decline between

2009 and 2014

Source: UNAIDS Estimates derived from GARPR 2015 data

New Paediatric HIV infections among the 21 Global

Plan countries dropped below 200,000 in 2014

1115

2126

46

66

1013

1923

2731

0

10

20

30

40

50

60

70

80

90

100

2009 2010 2011 2012 2013 2014

An

tire

tro

vir

al t

he

rap

y c

ov

era

ge

(%

)

Aggregate antiretroviral coverage for children (0-14) and pregnant women across 21 Global Plan priority Countries, 2014

Pregnant Women ART Coverage

Child ART Coverage


ART access for pregnant women has

Increased with the adoption and implementation of B+

BUT

Is the policy shift to Universal ART for

Pregnant and Breastfeeding women

the magic bullet to control MTCT?

� HIV testing still low; in 2013 only 44% of pregnant women were HIV tested,

73% of HIV+ women received any ARV in 2014, and 50% infants received

infant ARV prophylaxis.

Testing and ART for pregnant women remain inadequate

Adapted from WHO Global HIV/AIDS Updates

44%

73%

50%

94% 85%

96%

94

59

100

66 66

50

74

91

79

64

72

88

39

72

2720

11

45

12

31

0

66

5349

43 42 4138 37 37

30 29 29

22 2217 16

15

14 12 11

8

0

10

20

30

40

50

60

70

80

90

100

Nam

ibia

Botswana

South Africa

Swaziland

Zam

bia

Kenya

Zimbabw

e

Uganda

Mozambique

Malaw

i

Lesotho

Tanzania

Ghana

Ethiopia

Burundi

Côte d'Ivoire

Dem

ocratic Republic…

Angola

Nigeria

Cam

eroon

Chad

An

tire

tro

vir

al t

he

rap

y c

ov

era

ge

(%

)

Antiretroviral Coverage for children (0-14 years) and pregnant

women in 21 Global Plan priority countries, 2014

Pregnant

Women ART

CoverageChild ART

Coverage


But when you look at individual countries

there is a lot of heterogeneity in terms of coverage

PMTCT Coverage: • Significant reduction in MTCT rate

from 30% in 2009 and 5.3% in 2014

• ARV prophylaxis for pregnant

women has remained high at 84% in

2010 and 2014

• HIV exposed infants receiving ARV

prophylaxis for PMTCT increased

from 74% in 2010 to 88% in 2014

• Rapid expansion of Option B+ to

1,457 health facilities

Zimbabwe MTCT Rates & eMTCT Coverage, 2002-2013/4

Main Challenges:

Late booking and home deliveries

Loss to follow for HIV exposed infants

Goal: Reducing new Pediatric infections

by 90% & a MTCT of HIV < 5% end 2015

0

5

10

15

20

25

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2013

MTC

T R

ate

(%

)

Year

Trends in MTCT Rates at 6

weeks, 2002 - 2013

02000400060008000

100001200014000

started ART during

breastfeedingstarted ART in pregnancy

on ART pre-pregnancy

pregnant women

Source: Integrated HIV Program Report MOH,

Malawi April-June 2014

97% women

come to ANC but

~15% not tested

~23% new B+

women lost <6m

~30% new B+

women lost by 24m

pMTCT Cascade (Continuum) with Option B+Malawi HIV Programme Report April-June 2014

Retention on ART in adults in rural Zimbabwe

ICASA conference, Harare 2015

Retention on ART 12 months post initiation

N Deaths Losses Retention

Men & non B+ women 1,120 17 40 93% (91%-95%)

B+ women 386 3 55 79% (69%-87%)

0.00

0.25

0.50

0.75

1.00

0 3 6 9 12Time since ART initiation

Men & non B+ women

B+ women;

retention better

If start ART during

breastfeeding

Safety of EFV and TDF in pregnancy

Systematic review (11 studies; Antiretroviral

Pregnancy Registry data):

• outcomes of 1,290 live births in women

receiving EFV in 1st trimester;

no increase in overall birth defects

Insufficient data to exclude >3 X risk in low-

incidence birth defects – e.g. neural tube

defects

Systematic review (11 studies; Antiretroviral

Pregnancy Registry data):

• outcomes of 1,290 live births in women

receiving EFV in 1st trimester;

no increase in overall birth defects

Insufficient data to exclude >3 X risk in low-

incidence birth defects – e.g. neural tube

defects

Efavirenz

Risk of birth defects with EFV not increased

Tenofovir

TDF in pregnancy are limited

Concerns include renal toxicity, adverse birth

outcomes, effects on bone density

Systematic review of foetal exposure to TDF:

• In Antiretroviral Pregnancy Registry,

prevalence of 2.4% with TDF 1st trimester

exposure for all birth defects (same as

background)

• No association with neuro-developmental

outcomes in infants 9-15 month

• Lower 12 month growth with TDF exposure

• Promise trial had increased early deaths with

LPV/r and TDF

Concerns include renal toxicity, adverse birth

outcomes, effects on bone density

Systematic review of foetal exposure to TDF:

• In Antiretroviral Pregnancy Registry,

prevalence of 2.4% with TDF 1st trimester

exposure for all birth defects (same as

background)

• No association with neuro-developmental

outcomes in infants 9-15 month

• Lower 12 month growth with TDF exposure

• Promise trial had increased early deaths with

LPV/r and TDF

Ford N et al. AIDS, 2011; Ford N et al. AIDS, 2013; Ekouevi DK et al. JAIDS, 2011; WHO, Geneva Use of EFV in pregnancy, 2012; Antiretroviral Pregnancy Registry Steering

Committee http://www.APRegistry.com Siberry GK et al. AIDS, 2012; Gibb DM, et al. Pregnancy and infant outcomes among HIV-infected women taking long term ART

with and without tenofovir, PLoS Med 2012; Sirois PA, et al. Safety of perinatal exposure to antiretroviral medications: developmental outcomes in infants, PIDJ 2013.

Option B+ & eMTCT?

• Triple ART is best for reducing MTCT

• Coverage increasing but eliminating MTCT has a way to go

• B+ has benefits:

– Reduce pMTCT in future pregnancies

– simplicity; ↑rollout of ART for all alongside pMTCT

– reducing partner transmission

– improving maternal health

• The BIG risk is failure to retain in care and its consequences

– Involvement of male partners is important

In 6 priority countries, less than 1 in 20 HIV-exposed children had

early infant diagnostic services, and in 2, less than 1 in 10.

PMTCT Does Not End at Delivery:Infants Are Not Being Diagnosed

0

20

40

60

80

100

Swaziland

South Africa

Botswana

Namiba

Zambia

Zimbabwe

Kenya

Uganda

Lesotho

Mozambique

Ghana

Tanzania

Cameroon

Ethiopa

Angola

Burundi

Cote d'Ivoire

DRC

Nigeria

Chad

8978

58 56 55 5042 36 36 35 30 26 24 21 17 17 15 10 4 4

Source: Global Update

on the Health Sector

Response to HIV

2014

Access to Early Infant Diagnosis in 21 Priority Countries 2013

Only 44% of HIV-Exposed Infants

Received Early Infant Diagnostic

Testing

% w

ith v

iral te

st by a

ge 2

mo

05101520253035

0

10000

20000

30000

40000

50000

NASCOP, MOH Kenya, 2014

Early Infant Diagnosis Tests & Results by Entry point: Kenya 2014

9%6% 7%8%

21%31%

11%

Nu

mb

er o

f te

sts

% p

ositiv

e

Testing all Children admitted to Malnutrition and Acute

Care Units must be High priority

Stunting Wasting

Engagement with Communities is Vital� If parents (mother) dies, child often

returns to the village

� grandmother carers cannot easily travel

� Stigma and lack of male involvement

� In 30/1351 households in a survey in

North Uganda, informants “worried

a child in the household had HIV”

but “did not know where to test”

Engagement with Communities is Vital� If parents (mother) dies, child often

returns to the village

� grandmother carers cannot easily travel

� Stigma and lack of male involvement

� In 30/1351 households in a survey in

North Uganda, informants “worried

a child in the household had HIV”

but “did not know where to test”

What is Needed:

At Primary Health Facilities

� Knowledge of paediatric HIV

� On-site

mentorship

� Health system

strengthening

� Innovative ways to engage Men:

� At ANC

� Bring in the

children

0

10

20

30

40

50

60

70

80

90

100

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

rate/1000

Year

Infant Mortality Rates 2000-2015

Deaths = 1,043, Births = 24,082, Person Years = 26,772

Rate/Exposure Rate/Live Births

Deaths in Infants and 1-4year-olds

At home and in health facilities

Africa Centre Demographic surveillance

Rural KZN

South Africa

~40% infant die at home

~60% 1-4 year-olds die at home

WHY and what of?

How much is undiagnosed HIV

Despite good pMTCT coverage?

Summary: Early Diagnosis and Treatment

• Without early HIV diagnosis and ART, 50% children die <2 yrs

• Very early diagnosis & treatment reduces viral reservoirs and

has future potential BUT >90% infected children are to be

found outside pMTCT settings

• Provider initiated testing & linkage to care and ART needs to

be increased at multiple entry points

• …and near where children live (strengthening capacity at

lower level health centres (supply))

• Community mobilisation to understand HIV in children and

bring for testing and treatment (demand)

Outline

• Milenium Development Goals

• Prevention of Mother-To-Child Transmission (pMTCT)

• Where have we come from?

• Strategies for pMTCT

– From Option A to Option B plus

• Paediatric diagnosis & linkage to care

• Where are all the children?

• Management of HIV-infected adolescents and Prevention of HIV in adolescents

10,798 persons with perinatal HIV

living in the US in 2010CDC HIV Surveillance Report 2011

24%

76%

Perinatal HIV in the US and UK

0%

20%

40%

60%

80%

100%

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

Percent

Year

20+

15-19

10-14

5-9

1-4

<1

Age by year of follow-

up,1996-2013

…and UK/Ireland

Introduction

• Often , adolescents fall through

the cracks and prefer not to

seek care

• There is no primary health care

offered to adolescents in many

African Health care institutions

Responding to the needs of Teenagers

• Simpler and more ‘forgiving’ ART regimens:

– Once daily

– Long-acting Injectables

– ‘Weekend breaks’ (BREATHER Trial (PENTA 16))

• Non-judgemental information

• Peer support

UNICEF / UNAIDS

HIV Incidence Among Young WomenMore Than 1/3 New HIV Infections Globally Occur

Among Young Women in AfricaEstimated number of new HIV infections per week among young women

aged 15-24 years in East and Southern Africa, 2012

Source: PEPFAR and UNAIDS 2013

New Attention Being Paid to

Global Adolescent HIV Infections

Dec 2014: PEFPAR, Bill & Melinda Gates & Nike

Foundations announced $210 million initiative

to reduce new HIV infection in adolescent girls

& young women in 10 countries.

Feb 2015: UNAIDS, UNICEF, UNFPA,

WHO, PEPFAR, Global Fund, MTV Staying

Alive Foundation launched All-In:

Action against adolescent AIDS epidemic:

− Engergize, mobilize, empower youth

− Better data collection to inform programs

− Innovation to adapt services to youth

− Adolescent HIV on political agenda

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0

100,000

200,000

300,000

400,000

500,000

600,000

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

PM

TC

T c

overa

ge

New

HIV

in

fecti

on

s (

#)





In 2013: *240,000 children acquired HIV

~660 new infections/day

*3.2 million children <15 years

living with HIV

91% in SubSaharan Africa


not there yet!



Summary� PMTCT and eMTCT

� Increasing coverage is priority; some way to go to eMTCT

� Reduce new HIV infections in women & unmet family planning needs

� Infant/Child diagnosis is challenging

� Priority to increase testing and linkage to care outside pMTCT settings, near

where children live and to involve communites

� Adolescence through to adulthood

� There is an imperative to address wider needs of adolescents

� Reducing pregnancies and preventing HIV

� Long term follow up into adulthood is the responsibility of success

We have come a long way

BUT there is more work to be done!

Thanks to: Lynne Mofensen and

Shaffiq Essajee (WHO)

Documents

10.00 DiGibb RCOG 27Nov2015 · The Conduct of Placebo-Controlled Trials Raised New Controversies Despite controversy, several critical placebo-controlled trials of shorter AZT regimens