CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

in HIV- adolescents (from 5% to 18% and 54%; p<0.001). Self-reported use of tobacco increased with age but did not differ by HIV status (from 0.9% to 2% and 11% in PHIV+; 0% to 3% and 10% in HIV-). Self-report performed poorly in detecting use of the most common substances (Figure B). At enrolment and after 36 and 48 months, approximately 22% of PHIV+ had VL>50 copies/mL; 13% had VL>1000 copies/mL. Adjusting for age and gender, positive toxicology screen was not associated with VL at any time point. Conclusion: Among male PHIV+, the prevalence of substance use increased dramatically with older age but was lower than that of same-age, HIV- peers. Further efforts are needed to refine self-report measures and to explore the clinical and behavioral effects of substance use.

RAP2B, PIK3C2A and PIK3CB, were enriched in almost all pathways perturbed in viral suppressors, potentially serving as networking hubs. Among virally suppressed YWH, marijuana normalized all pathways and genes except for Protein Ubiquitination Pathway. Conclusion: HIV replication and long-term viral suppression display unique blood transcriptome bioprofiles. Surprisingly recreational use of marijuana normalized many pathways and genes dysregulated by HIV. Dorothy E. Dow 1 , Blandina T.Mmbaga 2 , John A.Gallis 3 , Elizabeth L.Turner 3 , Monica Gandhi 4 , Coleen K. Cunningham 1 , Karen O'Donnell 5 1 Duke University School of Medicine, Durham, NC, USA, 2 Kilimanjaro Christian Medical Centre, Moshi, Tanzania, 3 Duke Global Health Institute, Durham, NC, USA, 4 University of California San Francisco, San Francisco, CA, USA, 5 Duke University, Durham, NC, USA Background: There are increasing numbers of youth living with HIV (YLWH) with unaddressed mental health challenges. Mental health challenges are associated with poor antiretroviral therapy (ART) adherence which lead to unacceptably high mortality. Few evidence-based mental health interventions exist to address mental health challenges and improve HIV outcomes specifically for YLWH. Methods: This pilot group treatment trial, which individually randomized YLWH from two clinical sites in Tanzania, evaluated a mental health intervention, Sauti ya Vijana (SYV), compared to standard-of-care (SOC) for improving ART adherence and virologic suppression. SYV consisted of ten group and two individual sessions held weekly, delivered by lay counselors. Participants were living with HIV and 12-24 years of age. Demographics, mental health questionnaires (PHQ-9, SDQ, UCLA Trauma), stigma, self-report and objective measures of adherence (ART concentration in hair), and HIV RNA were obtained at baseline and 6-months (post-intervention). Potential effectiveness was assessed by comparing outcomes between arms in exploratory analyses using mixed effects modeling. Results: Between June 2016 and July 2017, 128 YLWH enrolled, of whom 105 were randomized and 93 (55 in SYV) followed-up at 6 months and were included in this analysis. Mean age of participants was 18.1 years with 51% female; 84% were infected perinatally. Exploratory analyses of effectiveness outcomes demonstrated change in mental health symptoms and internal stigma improved in both arms baseline to 6-months, but were not significantly different between arms. Self-reported adherence improved by 7.3 percentage points (95% CI: 2.2, 12.3) more in SYV compared to SOC; standardized levels of ART concentration increased by 0.17 ng/mg (95% CI: -0.52, 0.85) more in SYV compared to SOC. Virologic suppression (HIV RNA <400 copies/mL) at baseline was 65% in both arms, but increased to 75% in the SYV arm and stayed the same in the SOC arm (RR 1.13; 95% CI: 0.94, 1.36). Conclusion: YLWH worldwide are an important population, but often have poor HIV outcomes due to stigma and mental health difficulties. Very few interventions exist to improve outcomes in this critical population. This pilot trial of SYV demonstrated trends towards improvement in ART adherence, measured objectively, and virologic outcomes among YLWH in Tanzania supporting efforts to scale the intervention into a fully powered effectiveness trial.

836 PROMISING RESULTS FROM A PILOT RCT MENTAL HEALTH INTERVENTION FOR HIV-INFECTED YOUTH

Poster Abstracts

835 VIRAL SUPPRESSION AND MARIJUANA MODULATE TRANSCRIPTOME BIOPROFILE IN YOUTH WITH HIV Li Yin 1 , Ashok R. Dinasarapu 1 , Kai-Fen Chang 1 , John W. Sleasman 2 , Maureen Goodenow 1 1 NIAID, Bethesda, MD, USA, 2 Duke University, Durham, NC, USA Background: Viral suppression by antiretroviral therapy (ART) modulates many inflammatory pathways perturbed by HIV, but does not completely normalize inflammation. Substance use, particularly marijuana, affects pro-inflammatory pathways. A systems biology approach was used to define the transcriptome profiles associated with viral suppression and marijuana use in youth with HIV (YWH). Methods: The study included 20 YWH with long-term (3 years) viral suppression on ART (viral load < 50 copies), 8 virally suppressed YWH who regularly used recreational marijuana based on toxicology and self-report, 7 age-balanced YWH who failed the same 3-year ART regimen (median viral load 2,379 copies/ml), and 25 healthy, HIV-uninfected youth balanced for age, gender and race. Peripheral blood cell mRNA was profiled using Affymetrix HG-U133 Plus 2.0 Arrays. Differentially expressed genes (DEGs) were identified by Significance Analysis for Microarrays (FC > 1.3). Pathway enrichment analysis was performed using Ingenuity Pathways Analysis to identify enriched pathways (p < 0.001). Results: Active HIV-1 replication in 7 viral failures perturbed 127 pathways including 602 DEGs. Sustained long-term viral suppression by ART significantly reduced the perturbed pathways to 25 with 70 DEGs. Although 22 pathways remained perturbed in viral suppressors, ~70% genes dysregulated in viral failures were normalized, while DEGs identified in viral suppressors, including up-regulation of RAP2B, ITGB1, KLRD1 and KLRC3, and down-regulation of SLC8A1, E2F3 and COL4A3BP, were not observed in viral failures. Three pathways, including IL-6 signaling, macropinocytosis signaling and GDNF family ligand- receptor interactions, were unique to viral suppressors. Four genes, RAP2A,

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