Study design and participants
This retrospective cross-sectional study included data from adult PWH
with available plasma historical genotype resistance testing (HGRT) in
RT and PT genes performed prior LP, attending five Italian Clinics
(Amedeo di Savoia Hospital, Turin; L. Spallanzani IRCCS, Rome; Spedali
Civili General Hospital, Brescia; Santi Paolo e Carlo Hospital, Milan;
Umberto I Hospital, Rome) and one Clinic in the UK (University Hospital
Sussex NHS Foundation Trust, Brighton) between January 2001 to December
2021.
Eligible participants were age ≥18 years with at least one paired plasma
and CSF VL and on ART since at least one year. The temporal criterion of
ART duration was chosen to reduce the contribution of CSF slow
suppressor (higher CSF VL compared to plasma VL due to slower
suppression in CNS after the beginning of ART) to CVE. 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 plasma10. 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 CVE23–26)
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. In case of multiple episodes of CVE
per participant only the first one was included to avoid selection and
sampling bias. The institutional review board at each involved site
approved the research.