A Multicultural Caribbean United Against HIVAIDS Mother to Infant HIV Transmission: State of the Art

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A Multicultural Caribbean United Against
HIV/AIDSMother to Infant HIV Transmission
State of the Art

• Carmen D. Zorrilla, MD
• Professor OB-GYN
• UPR School of Medicine
• PI Maternal Infant Studies Center

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• We make a living by what we get. We make a life
  by what we give.Winston Churchill

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Possible Routes of Transmission
In-utero
At Birth
During Breastfeeding
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Incidence of Perinatally-Acquired AIDS United
States, 1985-2000
81
PACTG 076
decline
500
USPHS ZDV
recs
400
300
No. of Cases
200
100
0
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
00
Half Year of Diagnosis
(Reported through December 2000)
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Perinatal HIV TransmissionPuerto Rico (1990
2002)
Sources Ryan White Title IV Program, OCASET,
2002 Gamma Project CEMI
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Antiretroviral Therapy During Pregnancy
Indications

• Maternal
• Management of HIV Infection
• Fetal
• Prevention of Perinatal HIV
  Transmission

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Initial Perinatal Trials Focused on Prevention of
In Utero and Intrapartum Transmission
IP
AP
PP (baby, mother or both)
3d to 1 wk
36 wks
14 wks
6 wks
28 wks
076
NonBF
NonBF
Thai (Harvard)
NonBF
Thai (Harvard)
NonBF
Thai (Harvard), BMS
IvC (ANRS), PETRA, Thai (Harvard)
BF/NonBF
Thai (CDC), IvC (CDC)
NonBF/BF
PETRA, 012, SAINT
BF
PETRA
BF

PP Minimal duration? Is it needed?
AP Minimum duration? Is it needed?
IP Work alone?
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Initial Perinatal HIV Clinical TrialsEfficacy of
Regimens
Breast-fed
Formula-fed
AZT AZT/ AZT AZT NVP AZT/ NVP
AZT AZT/ AZT 3TC
3TC 3TC
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Effect of Breastfeeding on PMTCT Prophylaxis
37 No ARV, BF
22.5 AZT AP-IP
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18.1 AZT/3TC IP-PP
16.5
15.7 NVP IP-PP
14.9 AZT/3TC AP-IP-PP
11.8
8.9
8.6 076 AZT-no BF
5.7
1.6 316 comb-no BF
Infant Age
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Mother To Child Transmission (MTCT) Treatment
Options

• ZDV long course (076)
• ZDV short course (Thai 28 wks)
• ZDV shorter course (36wks)
• ZDV/3TC
• NVP single dose (SD)
• NVP plus infant ZDV
• ZDV short course /NVP SD
• HAART

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Single-dose NVP added to standard AZT regimen for
prevention of MTCT in Thailand Lallemant M et al.
11th Retrovirus Conf, Feb 2004 Abs 40LB
Women ZDV prophylaxis in 3rd trimester Infants
1 wk ZDV formula feeding
Mother-infant pairs n 1844

• Delivery before
• interim analysis
• Final as-treated

6.3
P .00026
1.1
2.8
2.0
NS
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Addition of Single-Dose Maternal/Infant NVP
toAZT is Most Effective at Higher Maternal RNA
Levels and lower CD4 counts (not shown)Lallemant
et al. 11th Retrovirus Conf, Feb 2004 (abs 40LB)
HIV RNA
Comparing Difference in Transmission Rates
AZT/Placebo-Placebo and AZT/NVP-NVP
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Short-Course AZT Single-Dose Maternal/Infant
NVPThailand Studies (Formula-Fed
Infants)Longer Maternal Therapy Lower
Transmission
Lallemant M et al. 11th Retrovirus Conf, Feb 2004
Abs 40LB
AZT Backbone
If mom lt4 wk AZT, infant gets 4 wks AZT
28 wk
1 wk
oral
NVP
NVP
Transmission 2.0 (95 CI 1.2-3.4) N693
Chalermchokcharoenkit et al. 11th Retrovirus
Conf, Feb 2004 (abs 96)
AZT Backbone
34-36 wk
oral
4 wk
NVP
NVP
Transmission 4.6 (95 CI 2.5-8.5) N220

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One Week of AZT Added to Single-Dose Infant NVP
Improves Efficacy When No Maternal IP NVP Dose
Taha T et al. Lancet 20033621171-7 -- NVAZ
Study Taha T. 2002 AIDS Conf, Barcelona Abs
ThPpD2146
Mother Infant
p0.03
20.9 15.3
Stratified Late Presenter vs Early
Presenter (got maternal NVP)
NB NVP
NB NVP
AZT 1 wk

15.4 15.3
NB NVP
IP NVP
NB NVP
AZT 1 wk
IP NVP
When maternal intrapartum NVP dose is received,
addition of AZT doesnt offer benefit
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PHPT-2 Single-Dose NVP Short-Course
AZTResponse to Treatment Sub-studyJourdain et
al. 11th Retrovirus Conf, Feb 2004 (Abs 41LB)

• After the PHPT-2 clinical trial, women were
  placed on NNRTI-based HAART (most d4T/3TC/NVP)
  for clinical and/or CD4 indications. There were
  213 women with prior SD NVP exposure and 42
  without.
• There were no differences in immunologic or
  virologic responses to lt400 RNA at 3 and 6 mo.
• Women with prior NVP exposure had lower response
  to lt50 at 6 months (only 27 women)
• Women with NVP resistance mutations had lower
  response overall

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Summary Virologic Response (lt400 lt50) to
NNRTI-Based Therapy by Prior History SD NVP
Jourdain et al. 11th Retrovirus Conf, Feb 2004
(Abs 41LB)
lt400 copies/mL
lt50 copies/mL
Baseline 3 Months 6 Months
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WHO Statement ARV and MTCT in resource-limited
settingsExpert consultation, Geneva, 5-6
February 2004

• Women who need ARV for their own health should
  receive it
• Women who do not need treatment should be offered
  ARV prophylaxis to prevent MTCT
• The most efficacious regimen is ZDV from 28 wks
  with single dose NVP at the onset of labor and
  single dose NVP plus one week ZDV for the infant

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WHO Statement ARV and MTCT in resource-limited
settingsExpert consultation, Geneva, 5-6
February 2004

• Alternative (but less efficacious) regimens
  include
• ZDV alone (28 wks) and 1 week for the infant,
• ZDV/3TC from 36wks, and 1 week for mother and
  infant, and
• Single NVP for mother and infant
• The selection should be based at national level
  based on efficacy, safety, drug resistance,
  feasibility and acceptability

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Mode of Delivery and Perinatal HIV Transmission
Meta-Analysis from 15 Prospective Cohort
StudiesThe International Perinatal HIV Grp. N
Engl J Med 1999340977-87
8,533 Mother-Infant Pairs from 15 Studies
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Effect of C/S on MTCT Transmission(PACTG 367
Chart Abstraction Study)

• Transmission rate compared for elective C-section
  vs all other modes of delivery (n3,081)
• HIV-1 RNA lt or gt 1000 copies/mL
• 1 drug vs multidrug therapy
• No difference between delivery modes in women
  with HIV-1 RNA lt 1000 copies/mL receiving HAART

Shapiro D, et al. 99
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Pregnancy in Perinatally HIV-Infected adolescents
and Young Adults PR 2002 (n 8 adolescents and
10 pregnancies) MMWR February 28, 2003/52(08)
149-151
All infants were HIV-uninfected
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Number of perinatally HIV-infected adolescents
and young adults reporting selected behavioral
and social characteristics (PR 2002)
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• Before making any important decision-declaring a
  war, moving with his companions to another plain,
  choosing a field in which to sow seed- the
  warrior asks himself How will this affect the
  fifth generation of my descendants?
• A warrior knows that everything a person does has
  enduring consequences and he needs to understand
  what kind of world he is leaving behind for that
  fifth generation.
• Paulo Coelho