•
Option B+ (Malawi)
Implementing Option B+: Malawi
•
Tenofovir phase in 1 st line( Zambia)
Accelerated global phasing out of d4T • d4T phase out in HIV programmes
•
Raising CD4 threshold to 350 cells (Ethiopia)
The ART programme in Ethiopia
No of ART sites (2006-2012) •
Viral Load roll out
(MSF and Kenya)
MSF UNITAID Funded Viral Load Project
(2013-2015)

OVER 50 NEW
RECOMMENDATIONS
TABLES, CHECKLISTS & ALGORITHMS
• Clinical
• Operational and Service
Delivery
• HIV testing & counselling
6 CHAPTERS: ALONG THE CONTINUUM OF CARE

Clinically relevant
•
Earlier initiation of ART (CD4 ≤ 500)
•
Immediate ART for children below 5 years
•
ART initiation for all pregnant and breastfeeding women (Option B/B+) and lifelong ART (Option B+)
•
Harmonization of ART across populations
(e.g., adults and pregnant women,
Option B/B+) and age groups
•
Simplified, fewer, and less toxic 1 st -line regimens (TDF/XTC/EFV)
Operationally relevant
•
Use of Fixed Dose Combinations as a preferred approach
•
Improved patient monitoring to support better adherence and detect earlier treatment failure ( increased use of VL )
•
Recommend task shifting, decentralization, and integration
•
Community based testing to complement broader HTC

Design an inclusive and transparent process
Discuss key data needed for evidencebased decisions
Examine key parameters for decision making
Review tools for costing and planning
Discuss implementation considerations

TARGET
POPULATION
(ARV-NAIVE)
HIV+ ASYMPTOMATIC
2010 ART GUIDELINES
CD4 ≤350 cells/mm 3
2013 ART GUIDELINES
CD4 ≤500 cells/mm 3 (CD4
≤ 350 cells/mm 3 as a priority)
STRENGTH OF
RECOMMENDATION &
QUALITY OF EVIDENCE
Strong, moderate-quality evidence
HIV+ SYMPTOMATIC
WHO clinical stage 3 or 4 regardless of CD4 cell count
No change
Strong, moderate-quality evidence
PREGNANT AND
BREASTFEEDING
WOMEN WITH HIV
CD4 ≤350 cells/mm 3 or
WHO clinical stage 3 or 4
Regardless of CD4 cell count or WHO clinical stage
Strong, moderate-quality evidence
HIV/TB CO-INFECTION
HIV/HBV CO-
INFECTION
HIV+ PARTNERS IN
SERODISCORDANT
COUPLE
RELATIONSHIP(S)
Presence of active TB disease, regardless of CD4 cell count
Evidence of chronic active HBV disease, regardless of CD4 cell count
No change
Strong, low-quality evidence
Evidence of severe chronic
HBV liver disease, regardless of CD4 cell count
Strong, low-quality evidence
No recommendation established
Regardless of CD4 cell count or WHO clinical stage
Strong, high-quality evidence

o
Systematic Review of 24 studies (3 RCTs, 21 observational ) o
Multiple countries throughout Europe, North America, Central &
South America, sub-Saharan Africa and Asia-Pacific o
Outcomes reported:
 mortality  C D4 increase
 progression to AIDS  viral suppression, failure, rebound
 progression to AIDS or death
 SAE and grade 3 or 4 lab
 non-AIDS defining cancer abnormalities
 serious non-AIDS events

Observational data RCTs – SMART / HPTN 052
Risk of Death or Progression to AIDS
Risk of Death
Clinical Trials (RCTs)
Low quality evidence for lower risk of progression to AIDS or death with early ART (2 RCTs)
Observational studies
Moderate quality evidence for lower risk of death
(13 studies) or progression to AIDS (9 studies) with early ART
Risk of
Progression to AIDS

Observational data Clinical Trial - HPTN 052
10
8
6
Unknown (n=3)
4
2
Not from partner
(n=7)
From partner
(n=29)
0
Early ART Late ART o
RCT to examine efficacy of ART in preventing
HIV transmission between discordant couples o
HIV+ partner had CD4 ≥ 350-550 cells/µL and was randomized to early vs. delayed ART o
Significant HIV prevention benefit – a 96% reduction in transmission.
o
1 genetically linked infection in early ART arm versus 29 infections in delayed arm.
Early ART Late ART
RCT and Observational data o
High to moderate quality evidence that treatment prevents sexual transmission of
HIV (1 RCT and observational data)

INITIATE ART REGARDLESS OF CD4 COUNT OR CLINICAL STAGE RECOMMENDATION
ADULTS WITH HIV…
CHILDREN < 5
YEARS OLD WITH
HIV
…and active TB disease
…and HBV co-infection with severe liver disease
…who are pregnant or breastfeeding
Strong, low-quality evidence
Strong, low-quality evidence
Strong, moderate-quality of evidence
…in a HIV serodiscordant partnership Strong, high-quality evidence
Infants diagnosed in the first year of life Strong, moderate-quality of evidence
Children infected with HIV between one and below five years of age
Conditional, very-lowquality evidence

Insufficient evidence and/or favorable risk-benefit profile for ART initiation at CD4 > 500 cells/mm 3 (or regardless of CD4 count) in the following situations:
 Individuals with HIV who are 50 years of age and older
 Individuals co-infected with HIV and HCV
 Individuals with HIV-2
 Key populations with a high risk of HIV transmission (e.g.: MSM, sex workers, IDU)
These populations should follow the same principles and recommendations as for other adults with HIV

FIRST-LINE REGIMENS (PREFERRED ARV REGIMENS)
TARGET
POPULATION
2010 ART GUIDELINES 2013 ART GUIDELINES
HIV+ ARV-NAIVE
ADULTS
AZT or TDF + 3TC (or
FTC) + EFV or NVP
HIV+ ARV-NAIVE
PREGNANT
WOMEN
AZT + 3TC + NVP or EFV
HIV/TB
CO-INFECTION
HIV/HBV
CO-INFECTION
AZT or TDF + 3TC (or
FTC) + EFV
TDF + 3TC (or FTC) + EFV
TDF + 3TC (or FTC) + EFV
(as fixed dose combination)
STRENGTH &
QUALITY OF
EVIDENCE
Strong, moderate-quality evidence

Preferred 1 st line regimen:
TDF + 3TC (or FTC) + EFV o
Simplicity: regimen is very effective, well tolerated and available as a single, oncedaily FDC and therefore easy to prescribe and easy to take for patients – facilitates adherence o
Harmonizes regimens across range of populations (Adults, Pregnant Women (1 st trimester), Children >3 years, TB and Hepatitis B,) o
Simplifies drug procurement and supply chain by reducing number of preferred regimens (phasing out d4T) o
Safety in pregnancy o
Efficacy against HBV o
EFV is preferred NNRTI for people with HIV and TB (pharmacological compatibility with TB drugs) and HIV and HBV coinfection (less risk of hepatic toxicity) o
Affordability (cost declined significantly since 2010)

Immunologic Response (48 weeks) o
Systematic review (10 RCTs): TDF+3TC (or
FTC)+EFV superior vs. other EFV containing regimens and vs. TDF/3TC+ PI/r on major outcomes - occurrence of SAEs, virologic and immunologic response (high to moderate quality of evidence)
Virological response (48 weeks)
Severe adverse events (48 weeks) o
Systematic review (7 RCTs, 27 observational):
NVP > 2 fold more likely to be discontinued due any adverse effect compared to EFV (moderate to low quality of evidence)
Discontinuation NVP vs. EFV o
Systematic review of preclinical data (5 studies): support pharmacological equivalence interchangeability of 3TC and FTC (low quality evidence)
Comparative efficacy 3TC and FTC

Evidence Summary: Safety of EFV and TDF in Pregnancy
EFV
No increased risk of birth defects with
EFV when compared with other ARVs o
Systematic review (including Antiretroviral
Pregnancy Registry), reported outcomes for 1502 live births to women receiving
EFV in the first trimester and found no increase in overall birth defects o
Excludes > 3 fold increased risk in overall birth defects
TDF o
Potential concerns include renal toxicity, adverse birth outcomes and effects on bone density o
Systematic review assessed the toxicity of fetal exposure to TDF in pregnancy
In Antiretroviral Pregnancy Registry, prevalence of all birth defects with
TDF exposure in 1 st trimester was
2.4% (same as background) o
Limited studies showed no difference in fetal growth between exposed/unexposed o
No studies of TDF among lactating women, who normally have bone loss during breastfeeding o
Current data reassuring o
More extensive studies ongoing
Source: Ford N et al. AIDS, 2011. Ford N et al. AIDS, 2013. Ekouevi DK et al.J AIDS, 2011. WHO, Geneva Use of EFV during pregnancy. 2012. http://www.who.int/hiv/pub/treatment2/efavirenz/en
Nightingale SL. JAMA, 1998. British HIV Association. Guidelines for the management of HIV infection in pregnant women. HIV Medicine. 2012. De Santis M et al. Arch of Int
Medicine, 2002.
Source: Antiretroviral Pregnancy Registry Steering Committee http://www.APRegistry.com Siberry GK et al. AIDS, 2012

H I V / A I D S

2001 2004
4 weeks AZT;
AZT+ 3TC, or
SD NVP
AZT from 28 wks + SD NVP
No recommendation
CD4 <200
2006 2010
AZT from 28wks
+ sdNVP
+AZT/3TC 7days
CD4 <200
Option A
(AZT +infant NVP)
Option B
(triple ARVs)
CD4 <350
Launch
July 2013
Option B or B+
Moving to ART for all PW/BF
CD4 <500
Move towards: more effective ARV drugs, extending coverage throughout MTCT risk period, and ART for the mother’s health

o
Limited coverage and implementation of PMTCT and ART for pregnant women in many high burden countries
•
~ 1.4 million HIV+ pregnant women
•
65% PMTCT ARV coverage
•
Limited ART in those eligible for treatment
•
High loss to follow-up along PMTCT cascade
•
Low ARV coverage during breastfeeding o
Complexity of Option A
•
Different treatment and prophylaxis regimens through pregnancy and breastfeeding
•
Difficulty of long-term NVP dosing for infants
•
Requirement for CD4 to determine eligibility
•
Follow up along the PMTCT cascade is very low
Steady progress reducing infant infections
600
500
400
300
200
100
0
2000
New child HIV infections, low and middle income countries (thousands)
2005 2010
• 2009: ~430,000 infant infections
• 2012: ~290,000 infant infections
• 2015: Global Plan target <40,000
2015 o
Current approach needs to be optimized to achieve universal access and elimination

“Option B+” “Option B”
All pregnant and breastfeeding women infected with HIV should initiate triple ARVs (ART), which should be maintained at least for the duration of mother-to-child transmission risk.
Women meeting treatment eligibility criteria should continue lifelong ART .
(strong recommendation, moderate-quality evidence)
For programmatic and operational reasons, particularly in generalized epidemics, all pregnant and breastfeeding women infected with
HIV should initiate ART as lifelong treatment.
(conditional recommendation, lowquality evidence)
In some countries, for women who are not eligible for ART for their own health, consideration can be given to stopping the ARV regimen after the period of mother-to-child transmission risk has ceased.
(conditional recommendation, lowquality evidence)

Rationale: Shift from Option A to B+ or B
BENEFITS FOR MOTHER AND CHILD
Ensures all ART eligible women initiate treatment
Prevents MTCT in future pregnancies
Potential health benefits of early ART for non-eligible women
Reduces potential risks from treatment interruption
Improves adherence with once daily, single pill regimen
BENEFITS FOR PROGRAM DELIVERY &
PUBLIC HEALTH
Reduction in number of steps along PMTCT cascade
Same regimen for all adults (including pregnant women)
Simplification of services for all adults
Simplification of messaging
Protects against transmission in discordant couples
Reduces sexual transmission of HIV Cost effective
Major issue now is not “when to start” or “what to start” but “whether to stop”

• Initiate all HIV+ pregnant and breastfeeding women on ART
• Operational and programmatic advantages to lifelong ART for pregnant and breastfeeding women (“B+”), particularly in settings with:
– Generalized epidemics
– High fertility (though need to strengthen FP)
– Long duration of breastfeeding
– Limited access to CD4 to determine ART eligibility
– High partner serodiscordance rates
• National programmes need to decide B or B+

2013 (no change from 2010)
National agencies should decide between promoting mothers with HIV to either breastfeed and receive ARV interventions or to avoid all breastfeeding
Where the national choice is to promote BF , mothers whose infants are HIV uninfected or of unknown HIV status should:
• exclusively breastfeed their infants for the first six months of life
• introduce appropriate complementary foods thereafter, and continue breastfeeding for the first 12 months of life
• breastfeeding should then only stop once a nutritionally adequate and safe diet without breast-milk can be provided
(strong recommendation, high-quality evidence for the first 6 months;
low-quality evidence for the recommendation of 12 months)

•
•
— Supply chain for ARVs (avoidance of stock-outs)
— Task-shifting for ART initiation
— Adherence, retention, follow up, linkages with chronic ART
— All MNCH sites become ART sites
•
Major challenge for PMTCT and MNCH settings:
• How to expand access to VL monitoring?
• How to utilize CD4 data, especially for women with high baseline CD4?

Summary of changes to recommendations:
What ART to Switch to
TARGET
POPULATION
HIV+ ADULTS
AND
ADOLESCENTS
HIV+
PREGNANT
WOMEN
2010 ART GUIDELINES
If d4T or AZT used in first-line
WHAT TO SWITCH IN ADULTS (PREFERRED REGIMENS)
TDF + 3TC (or FTC) +
ATV/r or LPV/r
2013 ART
GUIDELINES
STRENGTH & QUALITY
OF EVIDENCE
No change strong, moderatequality evidence
If TDF used in first-line
AZT + 3TC +
ATV/r or LPV/r
No change strong, moderatequality evidence
Same regimens recommended for adults
No change strong, moderatequality evidence
If rifabutin available
No change strong, moderatequality evidence
HIV/TB
CO-INFECTION
If rifabutin not available
Same regimens as recommended for adults
Same NRTI backbones recommended for adults plus
LPV/r or SQV/r with adjusted dose of RTV (i.e., LPV/r
400mg/400mg BID or SQV/r
400mg/400mg BID)
No change strong, moderatequality evidence
HIV/HBV
CO-INFECTION
AZT + TDF + 3TC (or FTC) + (ATV/r or LPV/r)
No change strong, moderatequality evidence