CSF Escape
CVE was observed in 51 unique participants (17.0%). CVE was detected a median of 14 months (9-28) after starting current ART (which was the first regimen in 27.4% of participants), and 4 years (2-6) from the first ART. Plasma VL was undetectable in 68.6% (Tab.1). The distribution of regimens is shown in Tab.1: 38 (74.5%) were on a PI-including regimen with boosted darunavir (35.3%), lopinavir (21.6%) and atazanavir (13.7%) as the most frequent PIs; four participants were on dual regimens: two on dolutegravir plus boosted-darunavir, and two on raltegravir plus either boosted-lopinavir and fosamprenavir; one participant was on monotherapy with boosted-darunavir. As shown in Tab.1, prevalence of plasma RAMs in the RT (52.9% vs 32.1%) and, to a lower extent, in the PT gene (17.6% vs 8.8%) was higher in participants with CVE. CSF RAMs followed a similar pattern among participants with available data (n=63; Tab.1).
Univariate analysis showed two-fold greater odds of CVE in participants with HGRT positive for plasma RAMs in RT (OR 2.38, p=0.005). Furthermore, participants with CVE were more likely to be of female sex and to belong to the 2001-2005 period, and less likely to be on ART from more than 10 years (Tab.2). No other variable in Tab.1 resulted associated with CVE risk. Despite CVE was more common in PI-including regimens, according to any ART classification and comparison, no statistically significant association between CVE and PIs use was observed (Fig.1). Similarly, no difference in CVE prevalence was observed comparing ART regimens by number of ARVs or pooled groups (mono/dual regimens, 3 classes regimens, PI-2NRTIs, NNRTI-2NRTIs, INSTI-2NRTIs and 4/5 ARVs regimens), nor between standard 3 drugs NRTI-backbone-based regimens versus less conventional regimens, nor by third class among standard 3 drugs NRTI-backbone-based regimens (data not shown).
Multivariable modelling showed almost four-fold increased odds of CVE (aOR 3.93, p<0.001) in participants with plasma RAMs in RT after accounting for age, sex, calendar year, duration of current and any ART, type of regimen, CPE score, plasma VL and CD4+ nadir. Duration of ART (aOR 0.14, p=0.017 for more than 10 years versus 1-2 years) was an additional independent risk factor (Tab.2).
The association between the presence of plasma RAMs in RT and CVE was confirmed in sensitivity analyses limited to participants with plasma VL≤50 copies/mL (n=202: aOR 4.35, p=0.003); in this subgroup, duration of ART was not an independent predictor of CVE, while CD4+ nadir (aOR 0.59 per every 100 cells/µL more, p=0.021) and age (aOR 0.65 per every 10 years more, p=0.047) were independently associated with CVE (Supp.Tab.2).