CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

414 Psychiatric Symptoms Are Common in Acute HIV and CorrelateWith Disease Biomarkers Joanna M. Hellmuth 1 ; Chun-Zi Peng 2 ;VictorValcour 1 ; Donn Colby 3 ; PonpenTantivayakul 3 ; Shelly Krebs 4 ; Praphan Phanuphak 5 ; Serena S. Spudich 6 ; Robert Paul 2 ; for the RV254/ SEARCH 010 Study Group 1 Univ of California San Francisco, San Francisco, CA, USA; 2 Missouri Inst of Mental Hlth, St. Louis, MO, USA; 3 SEARCH, Bangkok, Thailand; 4 Military HIV Rsr Prog, Bethesda, MD, USA; 5 Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand; 6 Yale Univ Sch of Med, New Haven, CT, USA Background: To assess the trajectory of anxiety and depression in acute HIV infection over six months following HIV diagnosis, and assess correlations between affective symptoms and blood and cerebrosinal fluid (CSF) disease biomarkers prior to treatment. Methods: A total of 123 participants were enrolled during acute HIV infection (Fiebig I-V) through the SEARCH010/RV254 cohort in Bangkok, Thailand. Participants completed the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire (PHQ-9) at baseline prior to combination antiretroviral therapy (cART) and again at weeks 4, 12, and 24 following diagnosis. Depression was defined as a score ≥ 8/21 on HADS-D or ≥10/27 on PHQ-9, with anxiety defined as a score ≥8/21 on HADS-A. Disease biomarkers of plasma and CSF HIV RNA levels, CD4 count, and plasma and CSF neopterin were obtained at entry, as was magnetic resonance spectroscopy (MRS). Res ults: At diagnosis, 46% of subjects met the clinical cutoff for depression on the PHQ-9 and 41% on the HADS-D, with 66%meeting the threshold for anxiety on the HADS-A. Affective symptoms decreased from baseline to week 12 without significant change fromweek 12 to week 24 (8% frequency on HADS-D, 18% frequency on PHQ-9, 17% frequency on HADS-A at the final visit). At baseline, higher average log 10 plasma HIV RNA was observed in participants experiencing depression on the HADS-D (5.9 vs. 5.7; p=0.006), or on the PHQ-9 (6.0 vs. 5.6; p=0.010) compared to those not experiencing significant depression. Similarly, those with baseline depression on the PHQ-9 had a lower CD4 count (330 vs. 414 cells/mm 3 ; p=0.024) and higher plasma neopterin, a marker of macrophage activation (3150 vs. 2118 pg/mL; p=0.026). CSF neopterin was higher on average in those experiencing baseline anxiety on the HADS-A (3218 vs. 1545 pg/mL; p=0.011; n=19). Examined as continuous variables, CSF neopterin correlated with PHQ-9 depression scores (r=0.47; p=0.044) and plasma neopterin correlated with HADS-A anxiety scores (r=0.304; p=0.037). No differences between groups were seen on MRS indices. Conclusions: In acute HIV infection, anxiety and depression are tightly linked to disease biomarkers, including indicators of plasma and intrathecal immune activation. These results confirm high rates of anxiety and depression in acute HIV that decrease with time in the setting of early cART, stabilizing at weeks 12 and 24. 415 Neurologic Signs and Symptoms Frequently Manifest in Acute HIV Infection Joanna M. Hellmuth 1 ; James L. Fletcher 2 ;VictorValcour 1 ; Eugène Kroon 2 ; Jintanat Ananworanich 3 ; Linda Jagodzinski 3 ; Duanghathai Suttichom 2 ; Nittaya Phanuphak 2 ; Serena S. Spudich 4 ; for the SEARCH 010/RV254 Study Group 1 Univ of California San Francisco, San Francisco, CA, USA; 2 SEARCH, Bangkok, Thailand; 3 Military HIV Rsr Prog, Bethesda, MD, USA; 4 Yale Univ Sch of Med, New Haven, CT, USA Background: To determine the incidence, timing, and severity of neurologic findings in pre-antibody seroconversion acute HIV infection, as well as persistence after early combination antiretroviral therapy (cART). Methods: A prospective cohort of participants identified through laboratory screening at an HIV/STD testing center in Bangkok, Thailand with Fiebig I-V acute HIV underwent structured neurologic evaluations, immediately initiated cART, and were followed with neurologic evaluations at 4 and 12 weeks after diagnosis. Concurrent viral and inflammatory markers in the blood and cerebrospinal fluid (CSF) were obtained, as was magnetic resonance imaging (MRI). Results: For the 139 participants, median estimated HIV infection duration at baseline evaluation was 19 days (range: 3-56). Seventy-three participants (53%) experienced one or more neurologic finding in the 12 weeks after diagnosis, with one developing a fulminant neurologic manifestation (Guillain-Barre syndrome). A total of 245 neurologic findings were noted, reflecting cognitive symptoms (33%), motor findings (34%), and neuropathy (11%). Nearly half of the neurologic findings (n=121, 49%) occurred at diagnosis, prior to cART initiation, and most of these (n=110, 90%) remitted concurrent with one month on treatment. Only 9% of neurologic findings (n=22) persisted at 24 weeks on cART. Nearly all neurologic findings (n=236, 96%) were categorized as mild in severity. Participants with neurologic findings had a higher mean plasma log 10 HIV RNA at diagnosis compared to those without neurologic findings (5.9 vs. 5.4; p=0.006), but no differences in markers of immune activation in blood or CSF. Four subjects with neurologic findings referable to the central nervous system (CNS) had undetectable CSF HIV RNA at diagnosis. No structural neuroimaging abnormalities were observed. Conclusions: Acute HIV infection is commonly associated with mild neurologic findings that largely remit while on treatment, and may be mediated by direct viral factors. Severe neurologic manifestations are infrequent in acute and early HIV in the setting of immediate treatment. 416 Male/Female Differences in Cognitive Function in HIV+ Individuals Pauline Maki 1 ; Leah Rubin 1 ; Gayle Springer 2 ; Ned Sacktor 3 ; Eric N. Miller 4 ;VictorValcour 5 ; MaryYoung 6 ; JamesT. Becker 7 ; Eric C. Seaberg 2 ; Eileen Martin 8 ; for the Neurocognitive Working Groups of theWomen’s Interagency HIV Study and the Multicenter AIDS Cohort Study 1 Univ of Illinois at Chicago, Chicago, IL, USA; 2 Johns Hopkins Bloomberg Sch of PH, Baltimore, MD, USA; 3 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA; 4 Univ of California Los Angeles, Los Angeles, CA, USA; 5 Univ of California San Francisco, San Francisco, CA, USA; 6 Georgetown Univ Med Cntr, Washington, DC, USA; 7 Univ of Pittsburgh, Pittsburgh, PA, USA; 8 Rush Univ Med Cntr, Chicago, IL, USA Background: Converging evidence suggests that HIV+ women are more vulnerable to cognitive impairment compared to HIV+men. Historically, comparisons of neurocognitive function between men and women living with HIV/AIDS have been difficult to interpret because of limited sample sizes and confounding by education, ethnicity, and socioeconomic status. Methods: We completed a longitudinal investigation of the independent and interactive effects of sex and HIV serostatus on neurocognitive measures including speed of information processing, executive function, and fine motor skills in HIV-infected and HIV-uninfected women from the Women’s Interagency HIV Study (WIHS) and men from the Multicenter AIDS Cohort Study (MACS) who were individually matched on race/ethnicity, HIV status, education, and age. The average number of visits for WIHS participants was 6.2 and for MACS was 9.2. Results were adjusted for other potential confounding factors including income, depression, and substance use. Results: The cohort consisted of 710 (429 HIV+) female and 710 male (429 HIV+) (67% NonHispanic-Black; 53% high school or less). In the multivariable analyses, we detected significant Sex by HIV Serostatus interactions on the Symbol Digit Modalities Test (SDMT) and both of the Trail Making Tests (TMT). Among HIV-uninfected individuals, women showed enhanced SDMT performance compared to men; however, among HIV-infected individuals that difference was eliminated (P = .007). On TMT Parts A and B, HIV-infected women performed significantly worse than HIV-infected men; however, among HIV-uninfected individuals the difference between women and men was smaller (Part A) or did not exist (Part B). Conclusions: These results suggest that HIV-infected women have greater cognitive vulnerabilities than HIV-infected men in the domains of processing speed and executive function. Our study also demonstrates that direct comparisons of neurocognitive outcomes among large cohorts of HIV+men and women are feasible and important to identify possible sex-specific profiles of neurocognitive impairments in HIV. 417 CNS Safety of Simplification to ATV/r+3TC in Virologically Suppressed HIV+ Patients Nicoletta Ciccarelli 1 ; Massimiliano Fabbiani 2 ; Eugenia Quiros Roldan 3 ; Manuela Colafigli 4 ; Antonella Castagna 5 ; Roberta Gagliardini 2 ; Andrea De Luca 6 ; Simona Di Giambenedetto 2 ; Roberto Cauda 2 ; for the ATLAS-M Study Group 1 Catholic Univ, Rome, Italy; 2 Inst of Clinical Infectious Diseases, Catholic Univ of Sacred Heart, Rome, Italy; 3 Univ of Brescia, Brescia, Italy; 4 San Gallicano Dermatological Inst, IRCCS, Rome, Italy; 5 San Raffaele Scientific Inst, Milan, Italy; 6 Univ of Siena, Siena, Italy Background: A concern of simplification to dual therapies is their low CNS penetrance. We explored the evolution of neurocognitive performance (NP) at week 48(w48) after treatment simplification to ATV/r+3TC versus maintaining 3-drugs ATV/r-based cART.

Poster Abstracts

158

CROI 2016