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Acute HIV CSF/Plasma RNA Ratios Are Variable and Greater Than in Chronic HIV
Joanna Hellmuth1, Serena Spudich2, Eugene Kroon3, Naponpon Sailasuta4, Somprartthana Rattanamanee3, Sukalaya Lerdlum5, Linda L. Jagodzinski6, Shelly J. Krebs7, Jintanat Ananworanich8, Victor G. Valcour1
1 Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States. 2 Department of Neurology, Yale University School of Medicine, New Haven, CT, United States. 3 SEARCH-Thailand, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 4 Department of Tropical Medicine, University of Hawaii, Honolulu, HI, United States. 5 Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 6 US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States. 7 US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Silver Spring, MD, United States. 8 US Military HIV Research Program, Bethesda, MD, United States.
Background: Clarifying the early dynamics of HIV invasion into the central nervous system (CNS) will inform understanding of the neurologic complications of HIV, and may facilitate cure interventions that rely on preventing establishment of viral reservoirs.
Methods: Forty-two Thai subjects identified in the acute phase of HIV infection (Fiebig I-V) had plasma and cerebrospinal fluid (CSF) samples for viral load and cytokine analysis, and magnetic resonance spectroscopy (MRS) an average of 16 days after self-reported estimated date of infection and all with measurable HIV RNA in plasma. We examined factors associated with ultra-low CSF HIV RNA (unquantifiable or undetected) compared to those with measurable CSF HIV RNA and examined the mean difference between log10 plasma and CSF HIV RNA during acute HIV infection (AHI). Pre-cART plasma and CSF viral loads were compared to that of 42 Thai cases evaluated just prior to cART initiation during chronic HIV.
Results: AHI subjects (n=42) were mean age of 29.8 (+/-7.8) and 9.5% female, whereas the 42 chronic cases were mean age of 34 (+/-6.6) and 54.8% female. 50% of chronic cases had a diagnosis of HIV-associated neurocognitive disorder (HAND). The mean difference between log10 plasma and CSF HIV RNA was 2.7 +/-1.4 for AHI compared to 0.8 +/-1.0 for chronic cases (p<0.0001). Ten of 42 AHI subjects had unquantifiable CSF HIV RNA and these cases tended towards the earliest stages of infection: Fiebig I (n=8); II (n=1); III (n=1). Individuals with undetectable CNS HIV RNA were then one-to-one matched by Fiebig stage to a random selection of cases with quantifiable CSF HIV RNA. Cases with unquantifiable CNS HIV RNA showed lower serum neopterin (p<0.05) and trended toward lower log10 CSF IP-10 (p<0.08).
Conclusions: The difference between log10 plasma and CSF HIV RNA (ratio of plasma/CSF) is significantly higher in acute compared to chronic HIV infection, with some individuals in the earliest stages of AHI manifesting ultra-low levels of HIV RNA in CSF. Subjects with initially ultra-low CSF HIV RNA trend towards lower markers of monocyte activation.