Transcript Women_Fri_Puga_Update DHHS - Florida/Caribbean AIDS

Pediatric HIV Treatment
Guidelines Update
Ana M. Puga, MD
Comprehensive Family AIDS Program
Children’s Diagnostic & Treatment Center
Fort Lauderdale, FL
Faculty, Florida/Caribbean AETC
Disclosures of Financial Relationships
This speaker has the following significant
financial relationships with commercial entities
to disclose:
•
Speaker’s Bureau: Abbott, Boehringer-Ingelheim, Gilead
This speaker will discuss off-label use or
investigational product during the program:
• Unlabeled use of drugs in pediatrics if pertinent to
discussion for all ARVs
This slide set has been peer-reviewed to ensure that there are no conflicts
of interest represented in the presentation.
Guidelines for the Use of Antiretroviral
Agents in Pediatric HIV Infection
• August 16, 2010 guidelines updated
August 11, 2011
• For full set of guidelines, visit the
AIDSinfo website at
http://aidsinfo.nih.gov/guidelines
What’s New in the Pediatric Guidelines?
• When to Start Antiretroviral Therapy
(ART)
– Recommendations for naïve infants
< 12 months and those older than 1 year
• What to Start; pediatric trial updates
• Monitoring updates for blips and lab
evaluations
• Toxicity management table updated
What’s New in the Pediatric Guidelines?
• Treatment Failure with focus on
adherence assessment/management
• Resistance Testing section expanded
• Pediatric Antiretroviral Drug Information
section reorganized and updated
At what ages should an exposed infant
be tested for HIV?
A. Birth, 1m, 2m, 3m
B. 2m, 4m, 6m, 18m
C. 14 days, 1m, 4m
D. Birth, 1m 4m, 6m
E. Birth, 14 days,
3m, 6m
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.
ART Initiation: Infants <12 Months
• Youngest children are at high risk of rapid
disease progression.
• Clinical and laboratory markers are poor
indicators of risk of rapid progression in infants.
• RCT and observational data suggest early ART
reduces risk of HIV progression and death.
• Limited information on appropriate ARV dosing.
August 2011
AETC National Resource Center, www.aidsetc.org
Indications for Initiation of ART
in Children <12 Months of Age
Criteria
Recommendation
Treat all, regardless of
clinical symptoms, immune
status, or viral load
Treat (AII)
Assess and discuss issues
associated with adherence
before therapy is initiated
(AIII)
August 2011
AETC National Resource Center, www.aidsetc.org
ART: Age ≥12 Months
• Children with AIDS or significant symptoms are at
high risk of disease progression and death; in
them, treatment should be initiated regardless of
immunologic or virologic status (AI)
August 2011
AETC National Resource Center, www.aidsetc.org
ART: Age ≥12 Months (2)
• Asymptomatic or mildly symptomatic children are at
lower risk of disease progression; CD4 count and
VL may be useful in determining need for ART.
• Younger age at initiation of therapy has been
associated with improved immune response and
rapid growth reconstitution.
• Higher CD4 count or % is associated with
better immune response to ART.
August 2011
AETC National Resource Center, www.aidsetc.org
ART: Age ≥12 Months (3)
• For asymptomatic children, ART now recommended
at higher CD4 count or %, though few data
available to define optimal CD4 threshold for
starting ART.
• At lower CD4 levels, recommendation to treat is
stronger (and supporting data are more substantial)
August 2011
AETC National Resource Center, www.aidsetc.org
ART: Age ≥12 Months (4)
• Factors to consider in deciding when to initiate
therapy in asymptomatic children >12 mos
– Increasing HIV RNA levels (e.g., approaching
100,000 copies/mL)
– CD4 count or percentage values approaching agerelated threshold for treatment
– Development of clinical symptoms
– Ability of caregiver and child to adhere to regimen
August 2011
AETC National Resource Center, www.aidsetc.org
At what age can you use the CD4 cut off
used for adults to start HAART in
asymptomatic children?
A. 6
B. 5
C. 12
D. 4
E. 13
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.
What is the CD4 cut off used in adults?
A. 350
B. 200
C. 500
D. 450
E. 600
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.
Indications for Initiation of ART
in Children ≥1 - <5 Years of Age
Criteria
Recommendation
AIDS or significant HIV-related symptoms (Clinical
Category C or most Clinical Category B
conditions) regardless of CD4 percentage/count
or plasma HIV RNA level
Treat (AI*)
CD4 <25% regardless of symptoms or HIV RNA
Treat (AII*)
Asymptomatic or mild symptoms plasma RNA
≥100,000 copies/mL regardless of CD4
percentage/count
Treat (BII)
Asymptomatic or have mild symptoms with a
plasma RNA <100,000 copies/mL and CD4
percentage >25%
Consider treatment
August 2011
(CIII)
AETC National Resource Center, www.aidsetc.org
Indications for Initiation of ART
in Children >5 Years of Age
Criteria
Recommendation
AIDS or significant HIV-related symptoms (Clinical
Category C or most Clinical Category B conditions)
regardless of CD4 percentage/count or plasma HIV
RNA level
Treat (AI)
CD4 ≤500, regardless of symptoms or HIV RNA
Treat
(AI forCD4 count <350 and
BII* for CD4 count 350–500)
Asymptomatic or have mild symptoms with a
plasma RNA ≥100,000 copies/mL regardless of
CD4 percentage/count
Asymptomatic or have mild symptoms with a
plasma RNA <100,000 copies/mL and CD4
percentage >25%
August 2011
Treat (BII)
Consider
treatment
(CIII)
AETC National Resource Center, www.aidsetc.org
Initial Combination Therapy
for ARV-Naïve Children
• Initial therapy should include at least 3
ARVs, from at least 2 drug classes, to
include:
– Either an NNRTI or a PI (boosted or
unboosted), plus
– A dual-NRTI backbone (AI)
August 2011
AETC National Resource Center, www.aidsetc.org
Which ARV was most recently
FDA approved for children?
A. Rilpivirine
B. Efavirenz
C. Raltegravir
D. Etravirine
E. Tenofovir
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.
Current ARV Medications
NRTI
PI
Fusion Inhibitor
 Abacavir (ABC)
 Didanosine (ddI)
 Emtricitabine (FTC)
 Lamivudine (3TC)
 Stavudine (d4T)
 Tenofovir (TDF)
 Zidovudine (AZT,
ZDV)
 Atazanavir (ATV)
 Darunavir (DRV)
 Fosamprenavir (FPV)
 Indinavir (IDV)
 Lopinavir (LPV)
 Nelfinavir (NFV)
 Ritonavir (RTV, /r)
 Saquinavir (SQV)
 Tipranavir (TPV)
 Enfuvirtide (ENF, T-20)
CCR5 Antagonist
 Maraviroc (MVC)
Integrase Inhibitor
 Raltegravir (RAL)
NNRTI
 Efavirenz (EFV)
 Etravirine (ETR)
 Nevirapine (NVP)
 Rilpivirine (RPV)
August 2011
 = FDA approved for pediatric treatment
AETC National Resource Center, www.aidsetc.org
NNRTI-Based Regimens
Advantages
Disadvantages
• Lower risk of
dyslipidemia and fat
maldistribution than
seen with PIs
• PI sparing
• More palatable
• Lower pill burden
• Risk of virologic failure if
exposed to single-dose NVP as
part of PMTCT
• Single mutation can confer highlevel resistance; cross-resistance
between EFV and NVP
• Risk of serious or life-threatening
rash and hepatitis (rare)
• Potential for multiple drug
interactions
August 2011
AETC National Resource Center, www.aidsetc.org
PI-Based Regimens
Advantages
Disadvantages
• NNRTI-sparing
• Metabolic complications
• Efficacy well
documented
• Potential for multiple drug
interactions
• Resistance requires
multiple mutations
• Higher pill burden
• Targets HIV at 2 steps
of viral replication
August 2011
• Poor palatability of liquid
formulations
AETC National Resource Center, www.aidsetc.org
Initial Treatment: Preferred Regimens
Children age >14 days
and <3 years1
2 NRTIs + LPV/r1 AI
Children age >3 years
2 NRTIs + EFV2
2 NRTIs + LPV/r
Children age >6 years
2 NRTIs + ATV (with low-dose RTV)
2 NRTIs + EFV2
2 NRTIs + LPV/r
AI
1 LPV/r
should not be given to neonates before a postmenstrual age (first day of the
mother’s last menstrual period to birth plus time elapsed after birth) of 42 weeks and a
postnatal age of at least 14 days.
² EFV is currently available only in capsule and tablet form and should be used only in
children age >3 years who weigh >10 kg. Not recommended for adolescent females who
are sexually active and may become pregnant unless adequate contraception can be
ensured.
August 2011
AETC National Resource Center, www.aidsetc.org
Initial Treatment:
Alternative Regimens
Children of any
2 NRTIs + NVP3
age
Children age
>6 years
2 NRTIs + DRV (with low-dose RTV) AI
2 NRTIs + FPV (with low-dose RTV)
NVP should not be used in postpubertal girls with CD4 count >250,
unless the benefit clearly outweighs the risk
3
August 2011
AETC National Resource Center, www.aidsetc.org
Initial Treatment: Regimens for Use in
Special Circumstances
 2 NRTIs + ATV unboosted (for treatment-naïve
adolescents age >13 years and body weight >39 kg)
 2 NRTIs + FPV unboosted (for children age >2 years)
 2 NRTIs + NFV (for children age >2 years)
 ZDV + 3TC + ABC*
* Test for HLA-B*5701 before initiation of ABC; do not give ABC to children who are HLAB*5701 positive. (AII*).
August 2011
AETC National Resource Center, www.aidsetc.org
Initial Treatment: 2-NRTI Backbone Options
Preferred
 ABC* + (3TC or FTC) (age >3 mos)
 TDF + (3TC or FTC) (adolescents age >12 years
and Tanner 4 or 5 only)
 ZDV + (3TC or FTC)
Alternative
 ddI + (3TC or FTC) BI
 TDF + (3TC or FTC) (adolescents age >12 years
and Tanner 3) BI
 ZDV + ABC*
 ZDV + ddI
Use in special  d4T + (3TC or FTC)
circumstances  TDF + (3TC or FTC) (adolescents age >12 years
and Tanner 2)
* Test for HLA-B*5701 before initiation of ABC; do not give ABC to children who
are HLA-B*5701 positive. (AII*).
August 2011
AETC National Resource Center, www.aidsetc.org
Initial ARV Therapy:
Components Not Recommended
Insufficient
Data for use
in Initial
Therapy
 Triple-class regimens, including NRTI
+ NNRTI + PI
 Maraviroc
 Etravirine
 Raltegravir
 Tenofovir (Insufficient data in children<12
years or children >12 and Tanner 1)
 Enfuvirtide
 EFV for children age <3
 Rilpivirine and rilpivirine-containing
regimens
August 2011
AETC National Resource Center, www.aidsetc.org
Initial ARV Therapy:
Components Not Recommended (2)
Potential
toxicity,
inferior
potency,
or
inconvenient
dosing
 ATV (unboosted) in children<13 years
and/or <39 kg
 IDV
 PTV
 NFV in children <2 years
 SQV
 RTV (full dose)
 EFV in first trimester of pregnancy or in
girls of childbearing potential
 NVP initiation in girls with CD4 >250 or
boys >400
 Dual PI regimens (full dose)
 NLF in age <2 years
August 2011
AETC National Resource Center, www.aidsetc.org
ARV Components Never Recommended as
Part of an ARV Regimen for Children
Components
Rationale
Exception
EFV in 1st trimester
of pregnancy or if
adequate
contraception
cannot be assured
Potential for
teratogenicity
When no other ARV
option is available and
potential benefits
outweigh risks
NVP in adolescent
girls with CD4 >250
or adolescent boys
with CD4 >400
Increased incidence of Only if benefit clearly
symptomatic hepatic
outweighs the risk
events
Unboosted SQV,
DRV or TPV
Poor bioavailability
Inferior virologic
activity
August 2011
Only if benefit clearly
outweighs the risk
AETC National Resource Center, www.aidsetc.org
ARV Components Never Recommended as
Part of an ARV Regimen for Children
Components
Rationale
Exception
ATV plus IDV
Potential additive risk
of hyperbilirubunemia
No exceptions
Dual-NNRTI
combinations
Enhanced toxicity
No exceptions
Dual NRTI
combinations: d4T
plus ZDV
Antagonistic effect on
HIV
No exceptions
Dual NRTI
combinations: 3TC
plus FTC
Similar resistance
profile and no additive
benefit
No exceptions
August 2011
AETC National Resource Center, www.aidsetc.org
ARV Regimens Never Recommended
for Children
Regimen
Rationale
Exceptions
Single-drug therapy
Rapid development of
resistance
Inferior antiviral activity
Prophylaxis for HIVexposed infants
3TC or FTC “bridging
regimen”
Two NRTIs alone
Rapid development of
resistance
Inferior antiviral activity
Not recommended for
initial therapy
In a child on 2 NRTIs with
good virological response
TDF plus ABC plus
(3TC or FTC)
High rate of early viral failure
No exceptions
TDF plus ddI plus
(3TC or FTC)
High rate of early viral failure
No exceptions
August 2011
AETC National Resource Center, www.aidsetc.org
How often should you monitor labs in
HIV infected children?
A. Every 2 months
B. Every 4-6 months
C. Every 1-2 months
D. Every 3-4 months
E. Every 6-12 months
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.
Monitoring of Children on ART
• Baseline (before ART)
– Clinical history, CBC and diff, chemistries
(incl. electrolytes, creatinine, calcium,
phosphorus, hepatic transaminases),
glucose, lipid panel and u/a.
– Urinalysis- NEW at baseline and reevaluate
every 6-12 months
– Genotype
August 2011
AETC National Resource Center, www.aidsetc.org
Monitoring of Children on ART(2)
• Within 1-2 weeks of starting new ARV regimen
– Screen for side effects, assess adherence (AIII)
• Within 4-8 weeks (AIII)
– Screen for side effects, evaluate virologic response (AIII)
– CD4/%, HIV RNA, CBC, chemistries (incl. renal panel
and liver function tests)
• For stable patients, follow up at least every 3-4
months (AII*)
– Monitor adherence, toxicity, efficacy (AII*)
• More frequent evaluation may be needed following
initiation or change in therapy (AIII)
* For children receiving nevirapine, serum transaminase levels should be measured every 2
weeks for the first 4 weeks of therapy, then monthly for 3 months, followed by every 3 to 4
months.
August 2011
AETC National Resource Center, www.aidsetc.org
Monitoring Viral Loads
– Panel noted that temporary viral load elevations
between the level of detection and 1,000 copies/ml
are often detected in children and are blips.
– “Blips”: Isolated episode of viremia <1000
copies/mL followed by return to viral suppression.
Common and not generally reflective of virologic
failure.
Toxicities and their management
• New sections added to table 17 on CNS
toxicity, gastrointestinal effects,
nephrotoxicity and peripheral nervous
system toxicity
• CNS: LPV/r EFV, RAL, TPV
• GI: Nausea/vomiting, diarrhea,
pancreatitis
• Renal: IDV, ATV, TDF
• Peripheral Nervous System : d4T, ddI
Overview of Treatment Failure (2)
– Evaluate the cause of treatment failure,
especially adherence (the #1 cause of
treatment failure)
– Not all ART failures require immediate change
in therapy (AII)
– Manage treatment failure in collaboration with
pediatric HIV specialist (AI*)
•
Bridging regimens
August 2011
AETC National Resource Center, www.aidsetc.org
Virologic Failure
– Incomplete virologic response to therapy or
viral rebound after achieving virologic
suppression
• Incomplete response to therapy:
– <1.0 log10 decline in HIV RNA from baseline after 812 weeks of ART; or
– HIV RNA >200 copies/mL after 6 months of ART; or
– Repeated HIV RNA above the level of detection
after 12 months of therapy using most sensitive
assay
August 2011
AETC National Resource Center, www.aidsetc.org
13 yr. old in clinic has viral load of 1975 copies/ml after 5
years of undetectable viral loads.
What would you do next?
A. Discuss adherence and
follow up in 1 month.
B. Discuss adherence,
adjust doses, test for
resistance and follow up
in 2-4 weeks.
C. Discuss adherence,
adjust doses and follow
up in 3 months.
D. Change medications and
discuss adherence.
0%
A.
0%
B.
0%
C.
0%
D.
Resistance Testing
• Recommended :
– Before initiation of ART for all treatment-naive
children (AII) (genotype preferred) (AIII)
– Before changing ART in patients with treatment
failure (AI*)
• In setting of viral failure, ensure patient is on
current regimen or within 4 weeks of
discontinuation (AII*)
August 2011
AETC National Resource Center, www.aidsetc.org
Resistance Testing
– Use phenotype (usually in addition to
genotype) for known or suspected complex
drug resistance (BIII)
• Absence of detectable resistance to a drug does
not insure its success
– Current assays are not sensitive enough to exclude
the presence of resistant virus
– ARVs history and previous resistance tests should be
reviewed when choosing new ART after virologic
failure (AII)
August 2011
AETC National Resource Center, www.aidsetc.org
Tropism (Viral Coreceptor) Assays
• Detects presence of CCR5 and CXCR4
coreceptors
• Standard test is phenotypic assay, requires
HIV RNA >1,000 copies/mL
– Genotypic assay available; few clinical data
• Should be performed before starting patient on
CCR5 antagonist (CCR5 antagonists not
effective in patients with CXCR4 virus) (AI*)
• Consider for patients who have virologic failure
on a CCR5 inhibitor (AI*)
August 2011
AETC National Resource Center, www.aidsetc.org
Pediatric Antiretroviral Drug Information
• Abacavir: Once daily dosing
16mg/kg/day max 600mg; in clinically
stable undetectable children
• Lamivudine: Once daily (300mg daily) for
youth ≥16 yrs who weigh ≥ 50kg
• Stavudine: Use only 30mg dose in
adolescents
• Tenofovir: Bone Mineral Density effects
and renal function effects updated in
children
Pediatric Antiretroviral Drug Information
• Efavirenz: Interpatient variabiltiy due to
CYP450 genes, TDM discussed.
• Nevirapine: Extended release not approved for
<18 yr.
• Rilpivirine: No pediatric data.
Pediatric Antiretroviral Drug Information
• Darunavir: Once daily only for naïve 1218 yrs if >40kg Dose at (800/100 mg).
• Lopinavir/ritonavir: Cardiovascular
toxicity in preterm infants- use only after
postmenstrual age of 42 weeks and a
postnatal age of at least 14 days.
• Saquinavir: Pretherapy ECG
recommended due to prolonged PR and
QT; do not use if has prolonged QT or on
meds that effect QT.
References
• Most slides in this presentation were
prepared by Mary Jo Hoyt, MSN; Carolyn
K Burr, EdD, RN; and Susa Coffey, MD for
the AETC National Resource Center in
August 2011.
• Panel on Antiretroviral Therapy and
Medical Management of HIV-Infected
Children. Guidelines for the Use of
Antiretroviral Agents in Pediatric HIV
Infection, August 11, 2011; Available at
http://aidsinfo.nih.gov/contentfiles/lvguideli
nes/PediatricGuidelines.pdf (Accessed
10-14-2012).
Perinatal HIV Treatment
Guidelines Update
Ana M. Puga, MD
Comprehensive Family AIDS Program
Children’s Diagnostic & Treatment Center
Fort Lauderdale, FL
DHHS Guidelines
• September 2011 guidelines updated July
31, 2012, including supplement update
on Safety & Toxicity of Individual
Antiretroviral Agents in Pregnancy
• For full set of guidelines, visit the
AIDSinfo website at
http://aidsinfo.nih.gov/guidelines
When do you test a pregnant
woman for HIV?
A. When she starts prenatal
care.
B. When she has an STI.
C. When she gets sick.
D. At entry into Prenatal
Care and at 28-32 weeks
or at delivery if not done
in third trimester
E. Every trimester.
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.
What’s New in the Perinatal Guidelines?
• New Clinical Trial results
• More info on Preconception Counseling,
including drug interactions and contraceptives
• Antepartum care expanded, including
management of naïve pregnant women and
those already on ARVs
• New ARVs recommended in preferred
category and category changes for other ARVs
What’s New in the Perinatal Guidelines?
• Intrapartum care changes- no IV ZDV
needed if woman is undetectable (BII)
• Postpartum care updates for infant
prophylaxis and monitoring
• Discussion of premastication
Strength of Recommendations
A: Strong
recommendation for
the statement
B: Moderate
recommendation for
the statement
C: Optional
recommendation for
the statement
I: One or more
randomized trials with
clinical outcomes and/or
validated
laboratory endpoints
II: One or more welldesigned, nonrandomized
trials or observational
cohort studies with longterm clinical outcomes
III: Expert opinion
Lesson Learned from Clinical Trials
• Breastfeeding and Nutrition (BAN) study
– Postpartum maternal triple drug prophylaxis vs. infant
NVP in women with CD4-cell counts ≥ 250 cells/mm3
– Arm 1 (control):
• Maternal ZDV/3TC for 1 week; infant single dose NVP +
ZDV/3TC for 1 week
– Arm 2: Control as above, then
• Maternal ZDV/3TC/LPV/r for 6 months
– Arm 3: Control as above, then
• Infant NVP for 6 months
– Results
• No significant difference between maternal triple-drug
prophylaxis (Arm 2) and infant NVP (Arm 3) at 28 and 48
weeks
August 2012
AETC National Resource Center, www.aidsetc.org
You have a 26 year old female who wants to start ARVs with
a “one pill a day” regimen. What do you discuss with her?
A. Proper dosing, side effects,
adherence, resistance and
cost
B. Proper dosing, side effects,
adherence, and resistance
C. Proper dosing, side effects,
adherence, resistance, and
preconception counseling,
including contraception
D. Proper dosing, side effects,
adherence and birth control
0%
A.
0%
B.
0%
C.
0%
D.
Preconception Counseling
• Contraception
– Updated information on hormonal contraceptive
interactions with ARVs
• Reproductive options for serodiscordant
couples
– Use of ART is recommended for the HIV-infected
partner, with maximal viral suppression achieved
prior to attempting conception
• For CD4-cell counts ≤550 cells/mm3 (AI)
• For CD4-cell counts >550 cells/mm3 (BIII)
August 2012
AETC National Resource Center, www.aidsetc.org
Preconception Counseling (2)
• Pre-exposure prophylaxis (PrEP)
– Recommendations
• Periconception administration of ARV PrEP may
offer an additional tool to reduce the risk of
sexual transmission (CIII).
• The utility of PrEP of the uninfected partner
when the infected partner is receiving ART has
not been studied.
– Discussion on PrEP includes information on
•
•
•
•
Studies
Counseling
Laboratory testing
Monitoring individuals on PrEP
August 2012
AETC National Resource Center, www.aidsetc.org
Antepartum Care
• Initial assessment of HIV-infected
pregnant women should include
– Screening for Hepatitis C and tuberculosis
infection
– A history of side effects or toxicities from
prior ARV regimens
• Use of effective ART to reduce
transmission to uninfected partners
– Discussion of HPTN 052 trial
August 2012
AETC National Resource Center, www.aidsetc.org
Antiretroviral Drugs During Pregnancy
• Modified drug categories: Preferred,
Alternative, Use in special circumstances
• Drugs that have changed categorization
– Didanosine and stavudine
• Use in special circumstances due to toxicity concerns
– Atazanavir
• Preferred due to increased information on safety
– Darunavir
• Alternative PI for use in ARV-naïve pregnant women
– Raltegravir
• Use in special circumstances when preferred or
alternative agents cannot be used
August 2012
AETC National Resource Center, www.aidsetc.org
ARV-Naïve HIV-Infected
Pregnant Women
• The decision to initiate an ARV drug
regimen in the 1st trimester or after 12
weeks gestation depends on (AIII)
– CD4-cell count
– HIV RNA levels
– Maternal conditions
• Earlier initiation of ARV combination
therapy may be more effective in
reducing transmission but risks and
benefits must be weighed
August 2012
AETC National Resource Center, www.aidsetc.org
HIV-Infected Pregnant Women Receiving
ARV Therapy
• Women receiving efavirenz as part of an
effective ART regimen may continue it
during pregnancy (CIII)
– The risk of neural tube defects is limited to
the first 5 or 6 weeks of pregnancy
• Most pregnancies are not recognized before 4 to
6 weeks
– ARV changes can lead to loss of viral
control and increased risk of perinatal
transmission
August 2012
AETC National Resource Center, www.aidsetc.org
Failure of Viral Suppression
• Discussion of the use of raltegravir in
late pregnancy for women with high viral
loads
– Efficacy and safety of this approach has not
been evaluated
– Concerns that the addition of a single agent
to a failing regimen may
• Increase resistance
• Decrease future effectiveness
August 2012
AETC National Resource Center, www.aidsetc.org
ARVs and Pregnancy Outcome
• Guidelines include a table of studies assessing
the association between ART and preterm
delivery (Table 7)
• 17 studies reviewed from sites throughout the
globe
• 10 associated with Preterm Delivery
• 7 Not associated with Preterm Delivery
• Association not yet confirmed given variability of
study data and results
• All but one US study (patients with advanced
disease) did not show an association
What is the recommended delivery option for a 30 y/o HIV+
G3P2 on ARVs with a viral load of 1800c/ml?
A. Vaginal delivery at term
B. C-section at term
C. Vaginal delivery at 38
weeks
D. C-section at 38 weeks
E. C-section at 38 weeks
with 3 hours of ZDV prior
to procedure
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.
When can IV ZDV be omitted in
the delivery process?
A. When the viral load near
delivery is <1000 copies/ml
B. When the viral load near
delivery is < 48 (<20)
copies/ml
C. When the viral load near
delivery is < 48 (<20)
copies/ml and a C-section
is planned
D. When a woman on
combination ARVs has
undetectable viral load
near delivery
0%
A.
0%
B.
0%
C.
0%
D.
Intrapartum Care
• IV zidovudine is no longer required for HIVinfected women receiving combination ARV
regimens who have HIV RNA <400
copies/ml near delivery (BII)
• HIV-infected women with HIV RNA ≥400
copies/ml (or unknown) near delivery
should be administered IV zidovudine
during labor regardless of mode of delivery
(AI)
– IV is the recommended route of zidovudine
administration
• Oral administration may be considered if IV is not
possible
August 2012
AETC National Resource Center, www.aidsetc.org
Postpartum Care
• Neonatal dosing recommendations for
– Zidovudine
– Nevirapine
• Neonatal prophylaxis regimens
– Discussion on the NICHD-HPTN 040 study
– Concerns about lopinavir/ritonavir in neonates
• Pharmacokinetic data on nevirapine in
preterm infants
August 2012
AETC National Resource Center, www.aidsetc.org
All these are ways HIV can be transmitted?
A. Blood contact, exchange of
sexual fluids, during
pregnancy and labor/delivery
B. Blood contact, exchange of
sexual fluids, during
pregnancy and
labor/delivery, and
breastfeeding
C. Blood contact, exchange of
sexual fluids, during
pregnancy and
labor/delivery, breastfeeding
and premastication
0%
A.
0%
B.
0%
C.
Postpartum Care (2)
• Management of the HIV-exposed infant
– Infants receiving zidovudine/lamivudinecontaining prophylaxis (AI)
• Higher risk for hematological toxicity (vs.
zidovudine alone)
• Recheck hemoglobin and neutrophil counts at 4
weeks after initiation of prophylaxis
– Health care providers should routinely
inquire about premastication of food fed to
infants, instruct HIV-infected caregivers to
avoid this practice, and advise on safer
feeding options (AII)
August 2012
AETC National Resource Center, www.aidsetc.org
References
• Most slides from the National AETC Resource
Center, What’s New in Perinatal Guidelines?,
August 2012, www.aidsetc.org (Accessed
10/14/2012).
• Panel on Treatment of HIV-Infected Pregnant
Women and Prevention of Perinatal
Transmission. Recommendations for Use of
Antiretroviral Drugs in Pregnant HIV-1-Infected
Women for Maternal Health and Interventions
to Reduce Perinatal HIV Transmission in the
United States. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/
PerinatalGL.pdf (Accessed 10/14/2012).