Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease.

NMUH Staff Publications

76

<div style="line-height: 17.999801635742188px;"><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">OBJECTIVE:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">The impact of different <span class="highlight">antiretroviral</span> agents on the risk of developing or surviving <span class="highlight">CNS disease</span> remains unknown. The aim of this study was to investigate whether using <span class="highlight">antiretroviral</span> regimens with higher <span class="highlight">CNS</span> <span class="highlight">penetration</span> effectiveness (CPE) scores was associated with reduced incidence of <span class="highlight">CNS disease</span> and improved survival in the UK Collaborative HIV Cohort (CHIC) Study.</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">METHODS:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">Adults without previous <span class="highlight">CNS disease</span>, who commenced combination <span class="highlight">antiretroviral</span> <span class="highlight">therapy</span> (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. <span class="highlight">CNS</span> <span class="highlight">diseases</span> were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations.</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">RESULTS:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a <span class="highlight">CNS disease</span> (HIVe 80; TOXO 59; CRYPTO 56; PML 54). <span class="highlight">CNS</span> <span class="highlight">diseases</span> occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death.</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">CONCLUSION:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">Clinical status at time of commencing cART influences <span class="highlight">antiretroviral</span> selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.</span></p></div>