CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

VL. Moreover, in those treated immediately, F I/II had markedly faster rates of seminal VL decay compared to F III/IV/V and F VI (p=0.072 and p=0.022, respectively) (Figure). There was no difference in rate of VL decay in plasma by Fiebig stage. Immediate ART was associated with significantly greater decline over 24 weeks in plasma IL-16, IP-10, TNFα, IL-1α, IL-2, IL-6,IL-10 and MIP1α, and IL-23p40 (p<0.05) but not TNFβ, SDF1α, MIP1β, MCP1, IL-8, IL-4, IL-1β, IFNα2a, IL-7, IL-12p70, or IFNγ. Change in cytokine levels was not strongly predicted by Fiebig stage, except for IL-23p40 and IL-16. Conclusion: ART initiation at the very earliest time point (in F I/II) has the greatest potential to impact HIV transmission through rapid reduction in seminal viral shedding. Semen VL decays slowly especially when ART is initiated in F VI, and is imperfectly predicted by plasma VL. The effects on plasma VL and inflammatory cytokines highlight the potential benefit of early ART initiation for individuals. These results underscore the need for frequent HIV testing with algorithms that detect acute infection in high-risk populations as part of treatment and treatment-as-prevention efforts.

Poster and Themed Discussion Abstracts

447 VALACYCLOVIR DOES NOT ATTENUATE CD4 COUNT DECLINE IN CART-UNTREATED HIV INFECTION

Darrell H. Tan 1 , Janet M. Raboud 2 , Leah Szadkowski 3 , Beatriz Grinsztejn 4 , Jose Valdez Madruga 5 , Pedro Cahn 6 , Simon Barton 7 , Amanda Clarke 8 , Wendy Zubyk 9 , Sharon Walmsley 10 1 St. Michael’s Hosp, Toronto, Ontario, Canada, 2 Univ of Toronto, Toronto, Ontario, Canada, 3 Toronto General Rsr Inst, Toronto, Ontario, Canada, 4 Inst Nacional de Infectologia (INI-Fiocruz), Rio de Janeiro, Brazil, 5 Centro de Referência e Treinamento em DST/AIDS-SP, Sao Paulo, Brazil, 6 Fundación Huesped, Buenos Aires, Argentina, 7 St. Stephen’s AIDS Trust, London, UK, 8 Brighton & Sussex Univ Hosps NHS Trust, Brighton, UK, 9 Canadian HIV Trials Network, Vancouver, British Columbia, Canada, 10 Univ of Toronto, Toronto, Ontario, Canada Background: Valacyclovir, a nucleoside analogue used for herpes simplex virus type 2 (HSV-2) infection, has been shown to decrease plasma HIV viral load (VL) regardless of HSV-2 serostatus. We studied the impact of valacyclovir on HIV disease progression in treatment-naïve HIV-infected adults. Methods: VALIDATE (VALacyclovir In Delaying Antiretroviral Treatment Entry, CTN-240) was a fully blind, multicenter, international 1:1 randomized controlled trial among treatment-naïve HIV-1-infected adults with CD4 counts of 400-900 cells/mm3 and not meeting contemporaneous recommendations for antiretroviral treatment (ART). Participants received valacyclovir 500 mg twice daily or placebo and were followed quarterly until there was documentation of either two consecutive CD4 counts ≤350 cells/mm3 or ART initiation for any reason. The primary analysis was a random effects model comparing the annual rate of CD4 count decline by study arm after adjusting for baseline CD4 count. Secondary analyses compared the rate of CD4 count percentage decline, HIV VL, HSV reactivations and drug-related adverse events. Upon recommendation by the DSMC, the trial was closed after release of the START trial results in August 2015. Results: We randomized 198 participants at 23 sites in Canada, Brazil, Argentina and the United Kingdom, including 72%MSM and 20%women. Median (IQR) age was 35 (30, 43) years. Baseline CD4 count was 592 (491, 694) cells/mm3 or 28% (23%, 33%), and VL was 4.04 (3.5, 4.5) log10 copies/mL. Over 276 person-years of follow-up, the CD4 count declined by 50 cells/mm3/year in the valacyclovir arm vs 59 cells/mm3/year in the placebo arm (p=0.65). Annual rates of decline in CD4 percentage were 1.2% and 1.69% for valacyclovir and placebo respectively (p=0.34). Valacyclovir decreased HIV VL by -0.22 log10 copies/ml overall (p=.01), but annual rates of change in plasma HIV VL were not different at 0.08 and 0.15 log10 copies/mL/year respectively (p=0.23). The proportions of patients with microbiologically confirmed HSV reactivations were not significantly different between study arms (1% vs 2%, p=.58). Grade 2 or higher drug-related adverse events occurred in 6% of valacyclovir and 7% of placebo participants (p=0.83). Conclusion: Valacyclovir did not slow HIV disease progression in ART-untreated adults, in contrast to trials using acyclovir in Sub-Saharan Africa, but did lower HIV VL by a small amount. These results provide further justification for early ART initiation in treatment naïve patients.

CROI 2017 186