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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. Oral Abstract Session Maternal Health and Paediatric Outcomes

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Alison Drake International AIDS Society Conference July 18, 2011

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  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Baseline and infant characteristics

  12. Postpartum plasma HIV-1 RNA levels Placebo Valacyclovir

  13. Postpartum plasma HIV-1 RNA levels Placebo Valacyclovir

  14. Postpartum plasma HIV-1 RNA levels Placebo Valacyclovir

  15. Postpartum plasma HIV-1 RNA levels 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)

  16. 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

  17. HIV-1 RNA detection in breast milk

  18. 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)

  19. 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)

  20. Risk of infant HIV-1 transmission n = 6 n = 4

  21. 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)

  22. 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

  23. 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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