Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Reversal of CSF HIV-1 Escape During Treatment of HIV-Associated Cryptococcal Meningitis in Botswana

Version 1 : Received: 22 May 2022 / Approved: 24 May 2022 / Online: 24 May 2022 (04:20:08 CEST)

A peer-reviewed article of this Preprint also exists.

Kelentse, N.; Moyo, S.; Molebatsi, K.; Morerinyane, O.; Bitsang, S.; Bareng, O.T.; Lechiile, K.; Leeme, T.B.; Lawrence, D.S.; Kasvosve, I.; Musonda, R.; Mosepele, M.; Harrison, T.S.; Jarvis, J.N.; Gaseitsiwe, S. Reversal of CSF HIV-1 Escape during Treatment of HIV-Associated Cryptococcal Meningitis in Botswana. Biomedicines 2022, 10, 1399. Kelentse, N.; Moyo, S.; Molebatsi, K.; Morerinyane, O.; Bitsang, S.; Bareng, O.T.; Lechiile, K.; Leeme, T.B.; Lawrence, D.S.; Kasvosve, I.; Musonda, R.; Mosepele, M.; Harrison, T.S.; Jarvis, J.N.; Gaseitsiwe, S. Reversal of CSF HIV-1 Escape during Treatment of HIV-Associated Cryptococcal Meningitis in Botswana. Biomedicines 2022, 10, 1399.

Abstract

Cerebrospinal fluid (CSF) viral escape has been poorly described among people with HIV-associated cryptococcal meningitis. We determined the prevalence of CSF viral escape and HIV-1 viral load (VL) trajectories in individuals treated for HIV-associated cryptococcal meningitis. A retrospective longitudinal study was performed using paired CSF and plasma collected prior to and during the antifungal treatment of 83 participants recruited at the Botswana site of the phase-3 AMBITION-cm trial (2018-2021). HIV-1 RNA levels were quantified then CSF viral escape (CSF HIV-1 RNA ≥ 0.5 log10 higher than plasma) and HIV-1 VL trajectories were assessed. CSF viral escape occurred in 20/62 (32.3%; 95% confidence interval [CI]: 21.9%-44.6%), 13/52 (25.0%; 95% CI: 15.2%-38.2%) and 1/33 (3.0%; 95% CI: 0.16%-15.3%) participants at days 1, 7 and 14 respectively. CSF viral escape was significantly lower on day 14 compared to days 1 and 7, p=0.003 and p=0.02, respectively. HIV-1 VL de-creased significantly from day 1 to day 14 post antifungal therapy in the CSF but not in the plasma (OR, 0.56; 95% CI: 0.41-0.77; p<0.001). CSF viral escape is high among individuals presenting with HIV-associated cryptococcal meningitis; however, antifungal therapy may reverse this, highlighting the importance of rapid initiation of antifungal therapy in these patients.

Keywords

HIV; cryptococcal meningitis; HIV-1 viral load; cerebrospinal fluid (CSF) viral escape; Botswana

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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