art regimen selection and treatment initiation for pmtct programs lara stabinski, md, mph medical...
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ART Regimen Selection and Treatment Initiation for PMTCT Programs
Lara Stabinski, MD, MPHMedical OfficerClinical Services
S/GAC
June 18, 2012
Technical Overview
1. PMTCT Options and ART Regimens Recognized in WHO PMTCT Programmatic Update 2012
2. Who needs ART?
3. Benefits of ART
4. New WHO Guidance on ART in Pregnancy
http://www.who.int/hiv/pub/mtct/programmatic_update2012/en/index.html
WHO PMTCT Update 2012
Women Eligible for ART Are At Highest Risk for Mother to Child HIV Transmission and Mortality
Eligible for ART
Not eligible for ART
MTCT by 6 wk 16.7% 5.0%
Proportion of MTCT by 6 wks
87.5% 12.5%
MTCT after 6 wks 17.0% 4.2%
Proportion of MTCT after 6 wks
87.5% 12.5%
Maternal mortality 24 mo post delivery
92% 8%
Cohort 1,025 pregnant women in Zambia prior to HAART availability
Analyzed MTCT/mortality by eligibility for ART with current WHO criteria (CD4 <350 or
WHO Stage 3 or 4)
Eligible68.1%
NotEligible31.9%
Kuhn L et al. AIDS 2010;24:1374-7
Who needs ART?
CD4 >350 (50-60% of
women)
CD4 <350 (40-50% of
women)
Eligible for Treatment40-50% of pregnant women
identified as HIV+ will be eligible for treatment for their own
health (CD4 <350)
Eligible for Prophylaxis50-60% of pregnant women identi-fied as HIV+ will have CD4> 350 and
should receive prophylaxis under Op-tions A or B
Prophlaxis GivenGenerally at ANC site
After CD4 results receivedAfter sample taken for CD4
ART GivenGenerally through referral to
treatment site
After CD4 results received:ART initiatedART (already initiated) contin-ues
Carter, RJ et al. JAIDS, 2010.
WHO Options A & BWho needs ART?
Transforming PMTCT: Option B+
“Recent developments suggest that substantial clinical and programmatic advantages can come from adopting a single, universal regimen both to treat HIV-infected pregnant women and to prevent mother-to-child transmission of HIV.”
-April 2012 WHO Programmatic Update on the use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants
10 PEPFAR countries are currently implementing, transitioning to, or considering Option B+
Who needs ART?
Option B+ provides full antiretroviral treatment for life for all HIV-positive pregnant women, regardless of CD4
Connecting PMTCT and Treatment
Pregnant Women represent an increasing proportion of all patients initiating combination antiretroviral therapy at PEPFAR sites. A recent study of PEPFAR programs in Kenya, Uganda, and Tanzania found that between 2002 and 2008 the prevalence of pregnancy at cART start increased from 2.6% to 16.0%.
0.0
5.1
.15
.22002 2004 2006 2008
Year of ART initiationEstimated proportion Observed proportion
Pro
por
tion
preg
nant
at
AR
T s
tart
Who needs ART?
Holmes, et al, CROI 2012
National ARV Coverage for PMTCT, 2010
BotswanaSouth Africa
NamibiaSwaziland
ARV Coverage 80%+Kenya
MozambiqueTanzania
ZambiaLesothoMalawi
ZimbabweCote d'Ivoire
UgandaARV Coverage 50-79%
GhanaCameroon
IndiaNigeria
EthiopiaAngola
BurundiChadDRC
ARV Coverage 0-49%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Source: Universal Access Report, 2011 % National ARV Coverage for PMTCT
Who needs ART?
Linking Eligible Women with ART
Malawi
Guyana
Cambodia
Haiti
Rwanda
South Afri
ca
Nigeria
Ethiopia
Uganda
Kenya
Tanzan
ia
Namibia
Swazi
land
Lesotho
Cote d'Iv
oire
Democra
tic Rep
ublic of C
ongo
Vietnam
Zimbab
we
Zambia
Angola
Burundi
Camero
onChina
Dominican Rep
ublic
Mozambique
South Su
dan
Botswan
aGhan
aIndia
IndonesiaRussi
a
Thail
and
Ukraine
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Percent of Total Women on ARVs Targeted to receive ART in FY 12
Who needs ART?
WHO 2010 Treatment Recommendations CD4<350 & for TB, ART initiation regardless of CD4 count
Starting Treatment Earlier in Resource Limited Settings Reduces Morbidity and Mortality (CD4 350 vs 200)
Severe, P et al. NEJM, 2010.
75% reduction in the rate of death 50% decrease in the incidence of tuberculosis
CIPRA HT-001
Benefits of ART
• CD4 <500 (Mostly Cohort Studies, sub-analysis of RCCT)– NA-ACCORD 6,278 patients*
• Delayed Treatment 70% increase progression to AIDS or Mortality
– ART-CC 45,691 patients, 18 cohort studies#• Delayed Treatment 30% increased progression to AIDS or Mortality
– HIV-CAUSAL 8,392 patients#• Delayed Treatment 38% increase progression to AIDS or Mortality
– CASCADE 5,527 patients• Early treatment decreased mortality by half
– SMART 249 patient subgroup• Deferred therapy were 4.6 times more likely to die or have an AIDS related event
– HPTN 052 1,763 patients• Approximately 40% reduction in events/mortality, benefits driven by
extrapulmonary TB
*Also showed mortality benefit >500# Did not show morbidity or mortality benefit >500
Decreasing Morbidity & Mortality With Earlier Treatment Benefits of ART
ART Potential Benefits to Maternal Health
• Maternal Mortality 24 months post-partum– Zambia study 2010 (n=14,110;ref group= HIV-)
HIV+ Mortality higherall CD4 Counts
• Cause specific mortality • higher TB, pneumonia, • meningitis, puerperal • sepsis, hemorrhage, PID
Benefits of ART
Hargrove JW et al. AIDS. 2010 Jan 28;24(3):F11-4.
<200200-400400-600600-800800-1K>1K
HPTN 052:Treatment Prevents HIV Transmission
Benefits of ART
HPTN052: Linked HIV-1 Transmissions: 27 vs 1
Cohen et al, NEJM 2011
Treatment as PreventionBenefits of ART
“A real game changer …”“People can say with a good deal more confidence that treatment is prevention.”
- Dr. Tony Fauci, US National Institute of Allergy and Infectious Diseases
Validation: HIV Incidence and ART Coverage
Tanser, CROI 2012
Benefits of ART
Every percentage point increase in ART coverage among all HIV+ adults in a community was associated with a 1.7% decline in the hazard of HIV acquisition (p <0.001) faced by an HIV– adult living in the same community
ART and Maternal Health Services
• Investigators assessed the effect of HIV programs on the utilization of maternal health services by HIV negative women over time: 257 PEPFAR-funded facilities in 9 countries (1907 quarters)
• There was a 1.3% increase in facility deliveries for a 10% increase in HIV patients in care per quarter.
• The number of facility deliveries was positively associated with the total number of ART patients in care in the past quarter, availability of HIV support groups, onsite CD4+ testing, and electronic HIV data systems.
• Evidence that building systems to deliver ART and other services can have beneficial effects.
Kruk et al, CROI 2012
Benefits of ART
WHO 2010 Guidance on ART Regimens for Pregnant Women
These guidelines also suggested that:Efavirenz (EFV) should not be used in the first trimester.Nevirapine (NVP) should not be used at CD4 counts >350
WHO Updated Guidance June 2012
Supports the use of EFV to Optimize and Simplify Treatment• EFV superior efficacy and tolerability compared to NVP• Substantial reduction in the price of EFV• Increasing availability as part of a once-daily FDC• Reassuring data on the risk of birth defects in pregnancy• Programmatic experience highlighting complications and
misconceptions about switching EFV to NVP in pregnancyhttp://www.who.int/hiv/pub/treatment2/efavirenz/en/index.html
http://www.who.int/hiv/pub/treatment2/efavirenz/en/index.html
http://www.who.int/hiv/pub/treatment2/efavirenz/en/index.html
Price Evolution of NVP and EFV
TDF In Pregnancy• Concern in pregnancy for fetal growth based on animal data at high
doses• PHACS Study (2012)
– N=2,000 births women TDF in Pregnancy– No greater risk of low birth weight, small head circumference or reduced
weight for gestational age– Found very small but significant difference in length for age at 1 year in
infants• Should be viewed in the context of potential increased mitochondrial
toxicity seen with infant AZT exposure and maternal anemia on AZT• May be especially useful where prevalence of HIV-HBV co-infection is
high• Can be used in once daily FDC
Acknowledgements
• S/GAC Clinical Team• PEPFAR Technical Working Groups (Adult
Treatment, PMTCT)