Valacyclovir suppression reduces breast milk and plasma HIV-1 RNA postpartum:
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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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Alison drake international aids society conference july 18 2011

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

  • 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 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 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 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

  • 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


Alison drake international aids society conference july 18 2011

Aims

  • 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

  • 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

  • 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


Alison drake international aids society conference july 18 2011

Screening, enrollment, 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


Baseline and infant characteristics

Baseline and infant characteristics


Postpartum plasma hiv 1 rna levels

Postpartum plasma HIV-1 RNA levels

Placebo

Valacyclovir


Postpartum plasma hiv 1 rna levels1

Postpartum plasma HIV-1 RNA levels

Placebo

Valacyclovir


Postpartum plasma hiv 1 rna levels2

Postpartum plasma HIV-1 RNA levels

Placebo

Valacyclovir


Postpartum plasma hiv 1 rna levels3

Postpartum plasma HIV-1 RNA levels

Placebo

Valacyclovir

p

2wk PVL 2- 6 wk rate of ∆

3.102.08

2.831.48

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

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


Hiv 1 rna detection in breast milk

HIV-1 RNA detection in breast milk


Breast milk hiv 1 rna levels

Breast milk HIV-1 RNA levels

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

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

n = 6

n = 4


Conclusions

Conclusions

  • 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

  • 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


Alison drake international aids society conference july 18 2011

Acknowledgments

  • 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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