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High prevalence of HIV persistence in CSF of adolescents and young adults with perinatally-acquired HIV and cognitive impairment in the IMPAACT 2015 study

Title
High prevalence of HIV persistence in CSF of adolescents and young adults with perinatally-acquired HIV and cognitive impairment in the IMPAACT 2015 study
Presenter
Ann Chahroudi
Authors
T. Wagner (1), C. Tierney (2), S. Huang (2), S. Nichols (3), K. Malee (4), N. Montañez (5), A. Coletti (5), H. Spiegel (6), M. Wilkins (7), L. Abuogi (8), M. Purswani (9), A. Bearden (10), A. Wiznia (11), A. Agwu (12), E. Chadwick (4), D. Richman (3), M. Gandhi (13), P. Mehta (14), B. Macatangay (14), S. Spector (3), S. Spudich (15), D. Persaud (12), A. Chahroudi * (16), IMPAACT 2015 Protocol Team
Institutions
(1) Center for Global Infectious Disease Research, University of Washington, Seattle, United States, (2) Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health, Boston, United States, (3) University of California, San Diego, San Diego, United States, (4) Ann & Robert H Lurie Children''s Hospital of Chicago, Chicago, United States, (5) IMPAACT Operations Center, FHI 360, Durham, United States, (6) Kelly Government Solutions, Contractor to the National Institute of Allergy and Infectious Diseases, Rockville, United States, (7) St. Jude Children''s Research Hospital, Memphis, United States, (8) University of Colorado, Denver, United States, (9) Bronx-Lebanon Hospital Center, Bronx, United States, (10) University of Southern California, Los Angeles, United States, (11) Jacobi Medical Center, Bronx, United States, (12) Johns Hopkins University School of Medicine, Baltimore, United States, (13) University of California, San Francisco, United States, (14) University of Pittsburgh, Pittsburgh, United States, (15) Yale University, New Haven, United States, (16) Emory University School of Medicine, Atlanta, United States

BACKGROUND: HIV persistence in the central nervous system (CNS) may be an important barrier to cure/remission strategies and may impact long-term cognitive outcomes in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT 2015 systematically examined AYAPHIV with cognitive impairment and receiving effective antiretroviral therapy (ART) to quantify HIV persistence in blood and cerebrospinal fluid (CSF).
METHODS: AYAPHIV (13-30 years old) with cognitive impairment and on suppressive ART were consented and enrolled into IMPAACT 2015, an IRB-approved U.S.-based cross-sectional, multi-site, exploratory, observational study. Cognitive impairment was defined as NIH Toolbox Fluid Cognition composite standard score >1 S.D. below the normative group mean. Participants underwent lumbar puncture (LP), phlebotomy, and hair collection. CSF and blood were measured for HIV-RNA and HIVpol/gag-DNA and 11 biomarkers of inflammation and neuronal injury. Hair was used to quantify ART exposure levels. Exact binomial confidence intervals (CIs) were calculated, and 41 comparisons evaluated with Wilcoxon rank sum tests.
RESULTS: Among 24 enrolled participants, 22 underwent LP, and 20/22 (91%) had successful CSF collection. 18 participants met ART suppression criteria, and had plasma HIV-RNA <20 copies/ml from entry through the day of LP. 9/18 (50%) were cisgender females and 14/18 (78%) were Black. Median (range) age was 20 years (13-27), time on ART 18.3 years (8.0-25.5), CD4 count 701 cells/mm3 (143-1342), and Fluid Cognition T-score 68 (53-80). HIV-DNA was detected in PBMCs in all participants. In CSF, 2/18 participants had detectable HIV-RNA, one of whom was quantifiable (5.6% 95% CI (0.1%, 27.3%)) and HIVgag and/or pol-DNA was detectable in 13/18 (72% 95% CI (47%, 90%)). Detectable HIV-DNA in CSF was associated with higher levels of HIVpol-DNA copies in PBMCs (medians 227, 27 per million cells, p=0.04), and trended with lower scores on a Fluid Cognition subtest measuring Inhibitory Control and Attention (medians 49, 65 p=0.09). Measured biomarkers and ART levels were not statistically associated with presence of detectable HIV-DNA in CSF.
CONCLUSIONS: Findings from IMPAACT 2015 suggest that the CNS is a site of HIV persistence in the majority of AYAPHIV with cognitive impairment, warranting further evaluation in pediatric HIV treatment and eradication studies.

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