Higher CNS Penetration-Effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid

OBJECTIVE:: To determine HIV-1 RNA in cerebrospinal fluid (CSF) of successfully treated patients and to evaluate if combination antiretroviral treatments (cART) with higher CNS penetration effectiveness (CPE) achieve better CSF viral suppression. METHODS:: Viral loads and drug concentrations of lopinavir, atazanavir and efavirenz, were measured in plasma and CSF. The CPE was calculated using two different methods. RESULTS:: We analysed 87 CSF samples of 60 patients. In 4 CSF samples HIV-1 RNA was detectable with 43 to 82 copies/mL. Median CPE in patients with detectable CSF viral load was significantly lower compared to individuals with undetectable viral load: CPE of 1.0 (range 1.0-1.5) versus 2.3 (range 1.0-3.5) using the method of 2008 (p=0.011), and CPE of 6 (range 6-8) versus 8 (range 5-12) with the method of 2010 (p= 0.022). The extrapolated CSF trough levels for atazanavir (n=12) were clearly above the IC50 in only 25% of samples; both patients on atazanavir/r with detectable CSF HIV-1 RNA had trough levels in the range of the presumed IC50. The extrapolated CSF trough level for lopinavir (n=42) and efavirenz (n=18) were above the IC50 in 98% respectively 78% of samples, including the patients with detectable CSF HIV-1 RNA. CONCLUSIONS:: This study suggests that treatment regimens with high intracerebral efficacy reflected by a high CPE score are essential to achieve CSF HIV-1 RNA suppression. The CPE score including all drug components was a better predictor for treatment failure in the CSF than the sole concentrations of PI or NNRTI in plasma or CSF