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

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 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.

The Presence of Resistance-associated Mutations in Reverse Transcriptase Gene is Associated with Cerebrospinal Fluid HIV-1 Escape: a multicentric retrospective analysis

“…]51 copies/mL; b) detectable plasma VL with concurrent CSF VL of at least 0.5 Log10 cp/mL higher than plasma 10 . PWH with any active inflammatory and/or infectious CNS disorder that could transiently increase CSF HIV RNA (such as CNS infections, autoimmune diseases or conditions increasing cells trafficking across the blood-brain barrier, as previously associated with secondary CVE [23][24][25][26] ) were excluded to focus on etiologic mechanisms underlying primary CVE. In case of availability of multiple CSF/plasma pairs per participant, the first pair only was included unless collected on different ART regimens at least one year apart.…”

Determining Potential Link between Environmental and Clinical Isolates of Cryptococcus neoformans/Cryptococcus gattii Species Complexes Using Phenotypic and Genotypic Characterisation

“…Cryptococcosis is an opportunistic infection in HIV/AIDS patients in sub-Saharan Africa with reported annual deaths of 75% in infected people [ 1 ]. Despite achievements of the UNAIDS 95-95-95 targets, cryptococcosis remains a significant challenge for HIV positive individuals in Botswana [ 24 ]. Thus, continued surveillance of the CnCg species complexes and rapid treatment of cryptococcosis is necessary.…”

“…Thus, continued surveillance of the CnCg species complexes and rapid treatment of cryptococcosis is necessary. In fact, recent findings suggest that effective HIV associated cryptococcosis antifungal treatment even without antiretroviral therapy can reverse CSF HIV escape [ 24 ].…”

The presence of resistance‐associated mutations in reverse transcriptase gene is associated with cerebrospinal fluid HIV‐1 escape: A multicentric retrospective analysis

“…CVE was defined as (a) plasma VL undetectable by clinical diagnostic assay (100% with lower limit of quantification of 50 copies/mL) and CSF VL ≥ 51 copies/mL; (b) detectable plasma VL with concurrent CSF VL of at least 0.5 Log10 cp/mL higher than plasma. 10 PWH with any active inflammatory and/or infectious CNS disorder that could transiently increase CSF HIV RNA (such as CNS infections, autoimmune diseases or conditions increasing cells trafficking across the blood-brain barrier, as previously associated with secondary CVE [23][24][25][26] ) were excluded to focus on etiologic mechanisms underlying primary CVE. In case of availability of multiple CSF/plasma pairs per participant, the first pair only was included unless collected on different ART regimens at least 1 year apart.…”