Browsing by Subject "Anti-retroviral agents"

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    Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression
    (Public Library of Science, 2021-05-13) Gisslen, Magnus; Keating, Sheila M.; Spudich, Serena; Arechiga, Victor; Stephenson, Sophie; Zetterberg, Henrik; Di Germanio, Clara; Blennow, Kaj; Fuchs, Dietmar; Hagberg, Lars; Norris, Philip J.; Peterson, Julia; Shacklett, Barbara L.; Yiannoutsos, Constantin T.; Price, Richard W.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Objective: To characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel of cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing a broad spectrum of systemic HIV-1 immune suppression, CNS injury and viral control. Methods: This is a cross-sectional analysis of archived CSF and blood samples, assessing concentrations of 10 functionally diverse soluble inflammatory biomarkers by immunoassays in 143 HIV-1-infected subjects divided into 8 groups: untreated primary HIV-1 infection (PHI); four untreated groups defined by their blood CD4+ T lymphocyte counts; untreated patients presenting with subacute HIV-associated dementia (HAD); antiretroviral-treated subjects with ≥1 years of plasma viral suppression; and untreated elite controllers. Twenty HIV-1-uninfected controls were included for comparison. Background biomarkers included blood CD4+ and CD8+ T lymphocytes, CSF and blood HIV-1 RNA, CSF white blood cell (WBC) count, CSF/blood albumin ratio, CSF neurofilament light chain (NfL), and CSF t-tau. Findings: HIV-1 infection was associated with a broad compartmentalized CSF inflammatory response that developed early in its course and changed with systemic disease progression, development of neurological injury, and viral suppression. CSF inflammation in untreated individuals without overt HAD exhibited at least two overall patterns of inflammation as blood CD4+ T lymphocytes decreased: one that peaked at 200-350 blood CD4+ T cells/μL and associated with lymphocytic CSF inflammation and HIV-1 RNA concentrations; and a second that steadily increased through the full range of CD4+ T cell decline and associated with macrophage responses and increasing CNS injury. Subacute HAD was distinguished by a third inflammatory profile with increased blood-brain barrier permeability and robust combined lymphocytic and macrophage CSF inflammation. Suppression of CSF and blood HIV-1 infections by antiretroviral treatment and elite viral control were associated with reduced CSF inflammation, though not fully to levels found in HIV-1 seronegative controls.
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    Poor retention and care-related sex disparities among youth living with HIV in rural Mozambique
    (Public Library of Science, 2021-05-21) Ahonkhai, Aima A.; Aliyu, Muktar H.; Audet, Carolyn M.; Bravo, Magdalena; Simmons, Melynda; Claquin, Gael; Memiah, Peter; Fernando, Anibal N.; Carlucci, James G.; Shepherd, Bryan E.; Van Rompaey, Sara; Yu, Zhihong; Gong, Wu; Vermund, Sten H.; Wester, C. William; Pediatrics, School of Medicine
    Background: There are few studies that characterize sex-related differences in HIV outcomes among adolescents and young adults (AYA) 15-24 years of age. Methods: We conducted a retrospective cohort study among AYA who enrolled in a comprehensive HIV program in Mozambique between 2012-2016. We assessed patients by sex and pregnancy/lactation status, comparing time to combination antiretroviral therapy (ART) initiation using Cox proportional hazard models. We employed multivariable logistic regression to investigate pre- and post-ART retention. Patients were defined as 'retained pre-ART' if they attended at least 3 of 4 required visits or started ART in the 6 months after enrollment, and 'retained post-ART' if they had any ART pickup or clinical visit during the last 90 days of the one-year follow-up period. Results: Of 47,702 patients in the cohort, 81% (n = 38,511) were female and 19% (n = 9,191) were male. Of the females, 57% (n = 21,770) were non-pregnant and non-lactating (NPNL) and 43% (n = 16,741) were pregnant or lactating (PL). PL (aHR 2.64, 95%CI:2.47-2.81) and NPNL females (aHR 1.36, 95%CI:1.30-1.42) were more likely to initiate ART than males. PL females had higher odds of pre-ART retention in care (aOR 3.56, 95%CI: 3.30-3.84), as did NPNL females (aOR 1.71, 95%CI: 1.62-1.81), compared to males. This was also true for retention post-ART initiation, with higher odds for both PL (aOR 1.78, 95%CI:1.63-1.94) and NPNL females (aOR 1.50, 95%CI:1.35-1.65) compared to males. Conclusions: PL females were most likely to initiate ART and remain in care post-ART in this AYA cohort, likely reflecting expansion of Option B+. Despite pregnancy and policy driven factors, we observed important sex-related disparities in this cohort. NPNL females were more likely to initiate ART and be retained in care before and after ART initiation than males. These data suggest that young males need targeted interventions to improve these important care continuum outcomes.