1 / 16

HSV-2 is associated with HIV acquisition among both placebo & vaccine recipients in the Step Study

HSV-2 is associated with HIV acquisition among both placebo & vaccine recipients in the Step Study. Ruanne V Barnabas, MBChB DPhil HIV Vaccine Trials Network, Seattle. 5 th IAS Conference on HIV Pathogensis, Treatment & Prevention 19-22 July 2009, Cape Town. Background: HSV-2-HIV synergy.

haley
Download Presentation

HSV-2 is associated with HIV acquisition among both placebo & vaccine recipients in the Step Study

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. HSV-2 is associated with HIV acquisition among both placebo & vaccine recipients in the Step Study Ruanne V Barnabas, MBChB DPhil HIV Vaccine Trials Network, Seattle 5th IAS Conference on HIV Pathogensis, Treatment & Prevention 19-22 July 2009, Cape Town

  2. Background: HSV-2-HIV synergy • HSV-2: most frequent cause of GUD, majority subclinical • HSV-2 and HIV • HSV-2 associated with increased risk of HIV acquisition1 • Men: RR=2.8 (95% CI: 2.1-3.7) • Women: RR=3.4 (95% CI: 2.4-4.8) • MSM: RR=1.6 (95% CI: 1.2-2.0) • HSV-2 increases HIV VL (0.3-0.55log10)2,3 1Glynnn JR, et al. (2009) Aids 2Duffus W, et al (2005) IJ STDs & AIDS 3Schacker T, et al (2002) JID

  3. Background: Step study • Step study • MRKAd5 HIV vaccine • 3000 high-risk HIV uninfected men & women in 34 sites • Primary outcome among 1,836 men1 • No difference in HIV acquisition • No difference in viral load setpoint • Subgroup analyses: increased risk of HIV acquisition among vaccinated, uncircumcised men & vaccinated Ad5 exposed men 1Buchbinder SP et al. (2008) Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet

  4. Research questions • What is the impact of HSV-2 seropositivity on HIV acquisition? (Analysis in placebo recipients; N=922) • What is the impact of HSV-2 seropositivity on the effect of the vaccine on HIV acquisition? (Analysis in placebo and vaccine recipients) • What is the effect of HSV-2 seropositivity on HIV VL? (Analysis in HIV seroconverters; N=87) • What is the effect of HSV-2 seropositivity on time to ART initiation? (Analysis in HIV seroconverters; N=87)

  5. Methods • Laboratory methods • HSV: Western blot (UWDVL)1 • Statistical analysis • 1,836 men, 88 HIV cases, infected prior to Oct 17th, 2007 • Kaplan Meier curves: HSV-2 as a risk factor for HIV acquisition & time to ART initiation • Cox proportional hazards regression: HSV-2 as a risk factor for HIV acquisition & time to ART initiation (stepwise selection of risk behavior variables) • Linear regression models: HSV-2 as a predictor of early pre-ART VL 1Ashley RL, et al (1988) Comparison of Western blot (immunoblot) and glycoprotein G-specific immunodot assay for detecting antibodies to HSV types 1 and 2 in human sera. J Clin Microbiol 26: 662-667.

  6. Q1: Impact of baseline HSV-2 seropositivity on HIV acquisition among placebo recipients; Kaplan Meier curves: Baseline HSV-2 seropositivity increased acquisition of HIV among placebo recipients Events observed HSV-2 negative: 18 HSV-2 positive: 17 *Log-rank test: p= 0.019

  7. Q1: Impact of baseline HSV-2 seropositivity on HIV acquisitionCox multivariate analysis results: HSV-2 seropositivity & age<30 increased risk of HIV acquisition among placebo recipients

  8. Q2: Impact of baseline HSV-2 seropositivity on HIV acquisition among placebo and vaccine recipients Kaplan Meier curves: HSV-2 increases risk of HIV acquisition among placebo & vaccine recipients Events observed HSV-2 negative: 50 HSV-2 positive: 36 *Log-rank test: p= 0.009

  9. Q2: Impact of baseline HSV-2 seropositivity on effect of vaccine on HIV acquisitionCox Proportional Hazards Model • Strong HSV-2 effect in univariate analysis: HR=1.7 (95% CI: 1.1- 2.7) • Adjusted for demographic, pre-specified & risk behavior variables (significant when added in a stepwise manner) • No significant interaction between HSV-2 & vaccine • Strong interaction between circumcision & vaccine (p=0.013)

  10. Q2: Impact of baseline HSV-2 seropositivity on HIV acquisition Cox results: HSV-2 positivity, N.America & Australia region, age<30, URAS£, UIAS£, Speed use in last 6 mnth^ & vaccine if uncirc’ed increased risk of HIV £UI/RAS: Unprotected insertive/receptive anal sex; ^prior to infection or last visit; * Vaccine x Circumcision Interaction significant (p=0.013)

  11. Q3: Impact of baseline HSV-2 seropositivity on HIV VL (all volunteers)Non-significant increase in HIV VL among HSV-2 seropositive compared to HSV-2 seronegative volunteers Linear regression Adjusted for vaccine, circumcision status, age, race, Ad5 immunity, & region: 0.3 log10 higher mean set point in HSV-2 seropositives (95% CI, 0.1 lower to 0.7 higher)

  12. Q4: Impact of baseline HSV-2 seropositivity on time to ART initiation; Kaplan-Meier Curves: No significant association between HSV-2 & time to ART initiation among placebo cases Cox HR for ART initiation by HSV-2 status stratified for region and circumcision status: HR=1.4 (0.5-4.5) unadjusted HR=1.5 (0.4-5.5) adjusted for age, race & Ad5 Months since infection diagnosis Num. at risk (HSV-2 negative) 18 14 (1) 12 (1) 8 (1) 1 (1) 1 0 Num. at risk (HSV-2 positive) 16 11 (3) 11 4 (3) 2 0 0

  13. Limitations • Risk behavior data • Self-reported risk behavior potentially subject to social desirability bias &/or recall bias • HSV-2 may be marker for increased behavioral (as well as biological) risk for HIV acquisition • VL, CD4 and ART initiation data are post-unblinding. • Current analysis among men only – future analyses will look at HSV-2 & HIV among women, but power will be limited

  14. Conclusions • HSV-2 infection increased HIV acquisition more than 2 fold • No significant interaction detected between HSV-2 & vaccine or circumcision • HIV viral load was not higher among HSV-2 seropositive compared to HSV-2 seronegative seroconverters • No significant association between HSV-2 serpositivity & HIV progression

  15. Thank you! Step study sites • STEP Volunteers • STEP Trial Sites Staff and Community Members • University of Washington Diagnostic Virology Laboratory • Rhoda Ashley Morrow, Stacy Selke & Anne Cent • SCHARP • Yunda Huang, Holly Janes, Maggie Wang, Alicia Sato, Liza Noonan, Peter Gilbert & Steve Self • HVTN+ • Susan Buchbinder, Jonathan Fuchs, Karen Mark, Martin Casapia, Jorge Sanchez, Ann Duerr & Larry Corey • Merck • Mike Robertson & Devan Mehrotra • University of Washington • Judy Wasserheit • HSV-2 manuscript team

  16. Q1: Risk factors for HSV-2 seropositivity at baseline Logistic regression (multivariate analysis): HSV-2 seropositivity associated with race/ethnicity, age>30, partners>4, UIAS & URAS

More Related