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Background

Effect of High-Dose HSV-2 Suppressive Therapy on Plasma HIV-1 RNA levels: a randomized, cross over trial 6 th IAS conference, Rome, Italy 17-20 th July, 2011 Kenneth K. Mugwanya Co-Investigators: Jared Baeten , MD , PhD Nelly Mugo , MBChB , M.Med ., MPH Elizabeth Irungu , MBChB

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  1. Effect of High-Dose HSV-2 Suppressive Therapy on Plasma HIV-1 RNA levels: a randomized, cross over trial • 6th IAS conference, Rome, Italy • 17-20th July, 2011 • Kenneth K. Mugwanya • Co-Investigators: • Jared Baeten, MD, PhD • Nelly Mugo, MBChB, M.Med., MPH • Elizabeth Irungu, MBChB • Kenneth Ngure, BSN, MPH • Connie Celum, MD, MPH

  2. Background • Standard-dose HSV-2 suppressive therapy (acyclovir 400 mg twice daily) reduces plasma HIV-1 levels by 0.25-0.50 log10 copies/mL. • If greater HIV suppression can be achieved with higher dose HSV-2 suppression, there may be a role for HSV-2 suppression to delay HIV disease progression and/or reduce HIV transmission. • Methods • Randomized, open label, crossover trial, 32 HIV-1/HSV-2 dually-infected • Not on ART, CD4 >250, detectable PVL: Kenya • HSV-2 suppression regimens: valacyclovir 1.5 gm Vs. acyclovir 400 mg both twice daily for 12 wks, then a 2 wk wash-out, and then the alternative for 12 wks. • PVL were measured weekly, with additional time points at day 1,2,& 3 post-drug initiation, and at day 3 post-drug termination. • Safety: AST, ALT, Creatinine, CBC, CD4 at screening and end of each drug period • Participants provided written informed consent. (ClinicalTrials.gov number NCT01026454)

  3. Results • At Enrollment: • 17 (53%) were women • Median age was 37 years (range 23-60) • Median CD4 count: 441 cells/ µL(range 283-977) • Mean plasma HIV levels: 4.10 log10 copies/mL (SD: 0.75). • Follow-up: mean plasma HIV-1 levels • Valacyclovir arm: 2.94 log10 copies/mL, (95% CI: 2.65, 3.24) • Acyclovir arm: 3.56 log10 copies/mL, (95% CI: 3.26, 3.85) • Mean difference between the study arms: • 0.62 log10 copies/mL lower in VAL. arm (95% CI -0.68, -0.55; p<0.001) • Valacyclovir Vs. Baseline PVL levels prior to HSV-2 suppression: • 1.23 log10 copies/mL decrease (95% CI, -1.38, -1.07; p <0.001) • Drug adherence and safety: • Participants took a median of 99.4% of tablets dispensed • lab. safety profiles were similar in both arms

  4. Plasma HIV-1 levels by treatment arm

  5. Conclusions • High dose valacyclovir was safe and significantly reduced plasma HIV-1 levels by an average of 0.6 log10 copies/mL compared to standard dose acyclovir, and a net >1 log10 copies/mL decrease compared to baseline HIV-1 levels prior to HSV-2 suppression. • Given the constraints on ART programs and preference of some HIV-1 infected individuals to delay ART initiation, the potential for high dose HSV-2 suppression to delay ART initiation warrants further evaluation.

  6. Acknowledgements • Study participants • The Bill and Melinda Gates Foundation (grant 26469) • US National Institutes of Health (grant R01 AI083034) • GlaxoSmithKline for study drug donation • Dr Ruth Wamae, and the staff at the Thika Partners Clinic • The Immunology Lab. at the University of Nairobi for HIV-1 PCR testing • The Clinical Trials Lab. University of Nairobi for additional lab. Testing • Dr. Larry Corey, University of Washington • Dr. Anna Wald, University of Washington • Dr. Meredith Potochnic, University of Washington

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