Mother to Child Transmission: Fidelia

1
Mother to Child Transmission Fidelia

• MTCT

2
Mother to Child Transmission Fidelia in her 30s

• Represents to clinic at 20/40 in 4th pregnancy
• Defaulted from care x 6/12self discontinued ART
• Asymptomatic and normal examination
• CD4 60 (5) and HIV VL gt100K
• Past medical history
• pansensitive TB (pulmonary blood CSF) fully
  treated
• ART exposed
• 3 previous full term normal deliveries
• HIV diagnosed in 3rd pregnancy and problems with
  adherence at that time and defaulted from care
• Hepatitis B negative Hepatitis C negative
  Syphilis negative

3
Mother to Child Transmission Fidelia ART
history and resistance

• Truvada and efavirenz (800mg while on TB
  medication)
• CD4 recovered from just over 250 x 106/L
• HIV viral load undetectable for gt 6/12
• Then viral load escape, reported good adherence
• Resistance
• Protease mutations L10I, I13V, K20I, M36I, I62V,
  L63P, L89M
• RT mutations A98G
• Mentioned that she wanted to get pregnant
• Switched from efavirenz to kaletra tablets
• Then defaulted from care
• Then represented pregnant and had stopped all
  medication

4
Mother to Child Transmission Fidelia What did
we do?

• PCP prophylaxis
• Co-trimoxazole prophylaxis of choice
• ?increased risk of congenital anomaly with first
  trimester exposure
• Jungmann EM et al, Sex Transm Infect. 2001
  Dec77(6)441-3
• Folic acid supplementation
• Hernandez-Diaz S et al, N Engl J Med. 2000 Nov
  30343(22)1608-14

5
Mother to Child Transmission Fidelia What about
ART?

• Recommenced her on Truvada and kaletra tablets
  (standard dose)
• CD4 count failed to improve
• HIV viral load failed to suppress
• Lots of support for adherence
• At 28/40
• HIV viral load lopinavir trough gt12000
• At 36/40
• CD4 65 (5) x 106/L HIV viral load 16K
• Reported good adherence

6
What would you do now?
7
Mother to Child Transmission Fidelia What we did!

• Urgent repeat resistance test
• Guidance on maternal and neonatal ART
• No new mutations
• Admit to hospital with child care support for
  observation of ART
• Elective c section
• Peri operative IV zidovudine as per PACTG 076
• Pre operative nevirapine 200mg stat
• Triple ART for neonate
• Keep neonate in hospital for ART

8
The role of ELCS in HAART era
Mother-to-child HIV transmission despite
antiretroviral therapy in the ANRS French
Perinatal Cohort. Warszawski J et al AIDS. 2008
Jan 1122(2)289-99
Mother-to-child transmission of HIV infection in
the era of highly active antiretroviral
therapy. European Collaborative Study Clin Infect
Dis. 2005 Feb 140(3)458-65
9
What about vaginal delivery in HAART era?
p0.150
10
The role of intrapartum prophylaxis
Mother-to-child HIV transmission despite
antiretroviral therapy in the ANRS French
Perinatal Cohort. Warszawski J et al AIDS. 2008
Jan 1122(2)289-99
intrapartum prophylaxis iv zidovudine or stat
nevirapine
11
Stat dose nevirapine - cons
Eshleman SH, et al Selection and fading of
resistance mutations in women and infants
receiving nevirapine to prevent HIV-1 vertical
transmission (HIVNET 012). AIDS 2001
Oct 1915(15)1951-7 Jackson JB, et al
Identification of the K103N resistance mutation
in Ugandan women receiving nevirapine to prevent
HIV-1 vertical transmission. AIDS 2000 Jul
2814(11)F111-5 Cunningham CK, et al Development
of resistance mutations in women receiving
standard antiretroviral therapy who received
intrapartum nevirapine to prevent perinatal human
immunodeficiency virus type 1 transmission a
substudy of pediatric AIDS clinical trials group
protocol 316. J Infect Dis 2002 Jul
15186(2)181-8 Palmer S et al. Persistence of
nevirapine-resistant HIV-1 in women after
single-dose nevirapine therapy for prevention of
maternal-to-fetal HIV-1 transmission. Proc Natl
Acad Sci USA. 2006 May 2103(18)7094-9 Jourdain
G, et al. Intrapartum exposure to nevirapine and
subsequent maternal responses to nevirapine-based
antiretroviral therapy. N Engl J Med 2004 Jul
15351(3)229-40
12
Stat dose nevirapine pros

• 41 reduction in MTCT vs oral ZDV at 18/12
• Jackson JB, et al Intrapartum and neonatal
  single-dose nevirapine compared with zidovudine
  for prevention of mother-to-child transmission of
  HIV-1 in Kampala, Uganda 18-month follow-up of
  the HIVNET 012 randomised trial. Lancet. 2003 Sep
  13362(9387)859-68
• Rapid viral decay
• Crosses the placenta
• Gingelmaier A et al, Placental transfer and
  pharmacokinetics of lopinavir and other protease
  inhibitors in combination with nevirapine at
  delivery, AIDS. 2006 Aug 2220(13)1737-43
• Pre exposure for the baby
• may be useful even if NNRTI resistance
  documented, particularly if adherence a problem
• Easier to administer than intravenous ZDV

13
Rapid viral decay
C Bell et al, Early viral load reduction in
pregnant women differs according to
antiretroviral regimen. Poster 656, 15th
Conference on opportunistic infections and
retroviruses, Boston 2008
14
What about keeping the baby in hospital for ART?

• Concern that without supervision the baby will
  not receive ART
• In Ireland the courts have supported making the
  child a ward of court in order to administer
  medication

15
Any other ideas?