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

Nametso Kelentse ORCID logo; Sikhulile Moyo ORCID logo; Kesaobaka Molebatsi; Olorato Morerinyane; Shatho Bitsang; Ontlametse T Bareng; Kwana Lechiile; Tshepo B Leeme; David S Lawrence ORCID logo; Ishmael Kasvosve ORCID logo; +5 more... Rosemary Musonda; Mosepele Mosepele; Thomas S Harrison; Joseph N Jarvis ORCID logo; Simani Gaseitsiwe; (2022) Reversal of CSF HIV-1 Escape during Treatment of HIV-Associated Cryptococcal Meningitis in Botswana. Biomedicines, 10 (6). p. 1399. ISSN 2227-9059 DOI: 10.3390/biomedicines10061399
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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 decreased significantly from day 1 to day 14 post antifungal therapy in the CSF but not in the plasma (β = −0.47; 95% CI: −0.69 to −0.25; 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.


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