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Valacyclovir suppression reduces breast milk and plasma HIV-1 RNA postpartum: results of a randomized clinical trial. Alison Drake International AIDS Society Conference July 18, 2011. Abstracts at IAS 2011. Oral Abstract Session Maternal Health and Paediatric Outcomes

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Valacyclovir suppression reduces breast milk and plasma HIV-1 RNA postpartum: results of a randomized clinical trial

Alison Drake

International AIDS Society Conference

July 18, 2011


Abstracts at ias 2011
Abstracts at IAS 2011 HIV-1 RNA postpartum:

  • Oral Abstract Session

    Maternal Health and Paediatric Outcomes

    • TUAB0202: Tuesday 2:30 – 4:00, MR 4

  • Poster Exhibitions

    • MOPE174: Monday 12:30 – 2:30

    • TUPE268: Tuesday 12:30 – 2:30


Mtct in non breastfeeding populations
MTCT in HIV-1 RNA postpartum: non-breastfeeding populations

Postnatal Tx rate

(6 mo)

Maternal HAART

Maternal HAART

1 - 2%

sdNVP

Maternal ZDV + 3TC (1 wk)

ZDV

1 - 2%

Pregnancy

Delivery

Postpartum


Mtct in breastfeeding populations
MTCT in HIV-1 RNA postpartum: breastfeeding populations

Cessation of BF

Postnatal Tx rate

(6 mo)

Maternal HAART

Maternal HAART or Infant NVP

3 - 5%

sdNVP

Maternal ZDV + 3TC (1 wk)

ZDV

8 - 10%

Pregnancy

Delivery

Postpartum


Mtct in breastfeeding populations1
MTCT in HIV-1 RNA postpartum: breastfeeding populations

  • Access to ARVs for PMTCT not universal

    • 53% coverage in low- and middle- income countries (WHO 2010)

  • Alternative strategies needed to reduce postnatal transmission

Cessation of BF

Postnatal Tx rate

(6 mo)

Maternal HAART

Maternal HAART or Infant NVP

3 - 5%

sdNVP

Maternal ZDV + 3TC (1 wk)

ZDV

8 - 10%

Pregnancy

Delivery

Postpartum


Hsv 2 infection in hiv 1 infected women
HSV-2 infection in HIV-1 infected women HIV-1 RNA postpartum:

  • Prevalence 75% to > 95%

  • Suppressive therapy

    • Reduces plasma HIV-1 RNA 0.25 - 0.5 log

    • 0.18 log greater reduction with valacyclovir (Ludema 2011)

    • Effect on breast milk HIV-1 RNA or MTCT unknown


Aims HIV-1 RNA postpartum:

  • To evaluate the effect of valacyclovir suppressive therapy administered during late pregnancy and for 12 months postpartum on:

    • Plasma HIV-1 RNA levels

    • Breast milk HIV-1 RNA detection and levels


Study design
Study design HIV-1 RNA postpartum:

  • Inclusion criteria

  • Procedures

  • Double blind RCT

    • 500 mg valacyclovir

    • or placebo bid

  • PMTCT ARVs

    • ZDV + sdNVP

  • HIV-1/HSV-2 seropositive

  • ≥ 18 years of age

  • HAART ineligible

    • CD4 > 250 cells/mm3

  • Seeking ANC in Nairobi, Kenya

  • Deliver and remain in Nairobi 12 months postpartum


Study design1
Study design HIV-1 RNA postpartum:

  • Inclusion criteria

  • Procedures

  • Double blind RCT

    • 500 mg valacyclovir

    • or placebo bid

  • PMTCT ARVs

    • ZDV + sdNVP

  • HIV-1/HSV-2 seropositive

  • ≥ 18 years of age

  • HAART ineligible

    • CD4 > 250 cells/mm3

  • Seeking ANC in Nairobi, Kenya

  • Deliver and remain in Nairobi 12 months postpartum

Screen

Enroll &

Randomize

Blood & breast milk

Delivery

Pregnancy

Postpartum

28-32wk

38wk

34wk

6wk

2wk

14wk

6mo

12mo


Screening, enrollment HIV-1 RNA postpartum: , and follow-up

April 2008 – June 2009

359 screened

Ineligible *

85 HSV-2

67 CD4

70 HAART

24 Residence

211 eligible

148 enrolled

74 placebo

74 valacyclovir

1 LTFU

73 included in analysis

1 LTFU

73 included in analysis

* not mutually exclusive



Postpartum plasma hiv 1 rna levels
Postpartum plasma HIV-1 RNA levels HIV-1 RNA postpartum:

Placebo

Valacyclovir


Postpartum plasma hiv 1 rna levels1
Postpartum plasma HIV-1 RNA levels HIV-1 RNA postpartum:

Placebo

Valacyclovir


Postpartum plasma hiv 1 rna levels2
Postpartum plasma HIV-1 RNA levels HIV-1 RNA postpartum:

Placebo

Valacyclovir


Postpartum plasma hiv 1 rna levels3
Postpartum plasma HIV-1 RNA levels HIV-1 RNA postpartum:

Placebo

Valacyclovir

p

2wk PVL 2- 6 wk rate of ∆

3.102.08

2.83 1.48

0.11 <0.001

0.60 lower (95% CI 0.92 – 0.28)


Postpartum plasma hiv 1 rna levels4
Postpartum plasma HIV-1 RNA levels HIV-1 RNA postpartum:

Placebo

Valacyclovir

p

6 wk – 12 mo rate of ∆ Mean (95% CI) difference

0.03

0.02 0.51 lower (0.73 – 0.30)

0.3 <0.001



Breast milk hiv 1 rna levels
Breast milk HIV-1 RNA levels HIV-1 RNA postpartum:

Placebo

Valacyclovir

Breast milk

Plasma

Median (IQR)

6 wk 14 wk

2.42 (1.70 – 3.35)1.70 (1.70 – 2.96)

1.70 (1.70 – 2.57) 1.70 (1.70 – 1.70)


Breast milk and plasma hiv 1 rna levels
Breast milk and plasma HIV-1 RNA levels HIV-1 RNA postpartum:

Placebo

Valacyclovir

Breast milk

Plasma

Median (IQR)

6 wk 14 wk

2.42 (1.70 – 3.35)1.70 (1.70 – 2.96)

1.70 (1.70 – 2.57) 1.70 (1.70 – 1.70)


Risk of infant hiv 1 transmission
Risk of infant HIV-1 transmission HIV-1 RNA postpartum:

n = 6

n = 4


Conclusions
Conclusions HIV-1 RNA postpartum:

  • Valacyclovir reduced

    • Early breast milk HIV-1 RNA detection

    • Plasma HIV-1 RNA 0.51 log

  • Plasma results consistent with other trials

  • Impact of valacyclovir on MTCT may differ from heterosexual transmission

    • Prolonged exposure to bodily fluids

    • 0.4 log lower viral load associated with reduced risk of postnatal MTCT (Neveu 2011)


Implications
Implications HIV-1 RNA postpartum:

  • Valacyclovir is an appealing intervention

  • Valacyclovir suppressive therapy, in conjunction with PMTCT ARVs, should be evaluated as an intervention to reduce postnatal MTCT and improve maternal health


Acknowledgments HIV-1 RNA postpartum:

  • Funding

  • NIH R03 5R03HD057773-02

  • NIH ARRA 5R03HD057773-02S1

  • University of Washington CFAR

  • P30 AI027757

  • CFAR STD Pre-doctoral Training Grant 5T32AI007140-33

  • Puget Sound Partners for Global Health

  • UW Royalty Research Fund

    Study participants

    Mathare staff

    DSMB

    GlaxoSmithKline

  • University of Washington

  • Carey Farquhar

  • Alison Roxby

  • Anna Wald

  • Grace John-Stewart

  • Barbra Richardson

  • Julie Overbaugh

  • Jane Hitti

  • Sandy Emery

    University of Nairobi

  • James Kiarie

  • Francisca Ongecha-Owuor


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