CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

208 DETERMINANTS OF SUBOPTIMAL IMMUNOLOGICAL RESPONSE AFTER ART INITIATION IN ACUTE HIV Ryan C. Handoko 1 , Donn Colby 2 , Eugène Kroon 2 , Mark de Souza 2 , Suteeraporn Pinyakorn 3 , Peeriya Prueksakaew 2 , Jennifer Chiarella 1 , Shelly J. Krebs 3 , Irini Sereti 4 , Victor Valcour 5 , Nelson L. Michael 3 , Nittaya Phanuphak 2 , Jintanat Ananworanich 3 , Serena S. Spudich 1 1 Yale University, New Haven, CT, USA, 2 SEARCH, Bangkok, Thailand, 3 US Military HIV Research Program, Silver Spring, MD, USA, 4 NIAID, Bethesda, MD, USA, 5 University of California San Francisco, San Francisco, CA, USA Background: Up to 30% of antiretroviral therapy (ART) treated individuals with suppressed chronic HIV infection fail to recover CD4+ T cell counts to a normal level (>500 cells/μL). We investigated if suboptimal immunological response (SR) also occurs when ART is started during acute HIV infection (AHI), and identified factors associated with SR. Methods: Thai AHI participants (n=289) underwent blood and optional cerebrospinal fluid (CSF; n=79) sampling followed by immediate ART. Those with ≥48 weeks of documented HIV-RNA <50 copies/mL were stratified by latest CD4+ T cell count to suboptimal response (SR; CD4<350 cells/μL), intermediate response (IR; 350≤CD4<500), and complete response (CR; CD4≥500). Clinical and laboratory parameters were assessed at baseline and latest study visit (median 144 weeks, range 60-420). CSF markers of immune activation, neuropsychological (NP) testing, and mood assessments were examined at 96 weeks. Mann-Whitney test was used for cross-sectional analyses between groups. Results: ART was started at a median 19 days post-infection and 3.8% (11/289) and 15.2% (44/289) had SR or IR, respectively. The degree of immunological response occurred early after ART in AHI and appeared to persist over time (Figure 1). At baseline, CD4+ T cell count was lower in the SR group compared to the CR group (median, 265 vs. 410 cells/μL, p=0.002), while blood HIV RNA, CD8+ T cell count, and CD4/CD8 ratio did not differ. After ART, CD8+ T cell count (median, 318 vs. 618 cells/μL, p=0.001) and CD4/CD8 ratio (median, 1.05 vs. 1.18, p=0.047) were lower in the SR group compared to the CR group. Blood sCD14 was elevated in SR and IR groups combined (n=3), compared to CR (n=26), at week 96 (median, 1.68 vs. 1.13 μg/L, p=0.008). Blood IL-6 was lower in SR and IR groups combined (n=8), compared to CR (n=69), at week 96 (median, 0.13 vs. 0.61 pg/mL, p=0.032). SR and CR did not differ in performance on NP testing or psychiatric indices at baseline or 96 weeks. However, baseline CSF neopterin was elevated in SR and IR groups combined (n=10), compared to the CR group (n=69, median, 2938 vs. 1623 pg/mL, p=0.050). Conclusion: Suboptimal immunological response, associated with low CD4 count at baseline and persistent low CD8 count during treatment, occurs in a small subset of individuals despite treatment in the earliest stages of infection. Furthermore, poor response is associated with neuroinflammation at baseline and systemic inflammation during treatment, as measured by sCD14 and CD4/ CD8 ratio.

209 CD4 INCREASE <100 CELLS/MM 3 DURING 2 YEARS OF ART IS ASSOCIATED WITH WORSE OUTCOMES Sol Aldrete 1 , Kirk A. Easley 2 , Jeong H. Jang 2 , Tian Dai 2 , Yi No Chen 3 , Jason Okulicz 4 , Brian K. Agan 5 , Mirko Paiardini 6 , Vincent C. Marconi 2 1 Medical College of Wisconsin, Wauwatosa, WI, USA, 2 Emory University, Atlanta, GA, USA, 3 Atlanta VA Medical Center, Decatur, GA, USA, 4 Brooke Army Medical Center, San Antonio, TX, USA, 5 Uniformed Services University of the Health Sciences, Bethesda, MD, USA, 6 Emory Vaccine Center, Atlanta, GA, USA Background: Immune non-responders (INR) have increased morbidity and mortality despite antiretroviral therapy (ART). There is no consensus in the literature on how best to define INR and most definitions have not been associated with clinical endpoints. We aimed to identify the CD4 T-cell recovery pattern most highly predictive of a composite clinical outcome. Methods: We included treatment naïve patients who remained virologically suppressed for at least 2 years after starting ART from three large cohorts with distinct patient characteristics [HIV Atlanta VA Cohort Study (n=262), The US Military HIV Natural History Study (n=1014), and The Infectious Disease Program Cohort of the Grady Health System in Atlanta, Georgia (n=1146)]. A composite clinical outcome was created to indicate mortality, AIDS and non-AIDS events. The CD4 T cell recovery pattern most highly predictive of the composite outcome was modeled. Rates of CD4 increase were obtained using a mixed-effects model specifying that CD4 counts follow a linear model regression over time, with a random intercept and slope for each patient. Additionally, a two-stage modeling and joint modeling was used to enable both longitudinal repeated CD4 cell count and clinical endpoint data to be modeled together. Results: The total cohort included 2,422 patients, 86.9%were male, 61.6% were black, with a median age of 37 years at ART start. The average yearly linear CD4 cell count rate of increase was 102 cells/mm 3 /year during two years of continuous ART (joint modeling). The composite endpoint rate decreased 20% per 100 cells/mm 3 /year increase in CD4 count (adjusted hazard ratio [aHR] = 0.80, 95%CI: 0.65-0.99, p =0.04). The rate of CD4 increase was highly associated with the composite endpoint for any given fixed intercept value, CD4 nadir or CD4 baseline. Immune responders (CD4 cell count ≥ 100 cells/mm 3 /year) had lower clinical endpoint rates (aHR = 0.73, 95%CI: 0.56-0.94, p =0.01) compared to INR (two-stage modeling). Conclusion: CD4 T cell counts are prone to measurement error and high patient variability, which makes the modeling approaches attractive. We proposed defining INR as failure to increase ≥ 100 cells/mm 3 /year during the first two years on ART.

Poster Abstracts

210 EFFECTS OF LONG-TERM ART ON SIVAGMSAB-INFECTED PIGTAILED MACAQUES Benjamin Policicchio 1 , Paola Sette 1 , Ranjit Sivanandham 1 , Cui Ling Xu 1 , Tianyu He 1 , Egidio Brocca-Cofano 1 , Kevin D. Raehtz 1 , Ellen P. Penn 1 , Tammy Dunsmore 1 , George S. Haret-Richter 1 , Russell Tracy 2 , Cara Wilson 3 , Alan Landay 4 , Cristian Apetrei 1 , Ivona Pandrea 1 1 University of Pittsburgh, Pittsburgh, PA, USA, 2 University of Vermont, Colchester, VT, USA, 3 University of Colorado, Aurora, CO, USA, 4 Rush University Medical Center, Chicago, IL, USA

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CROI 2018