|Authors: Hammond ER, Crum RM, Treisman GJ, Mehta SH, Clifford DB, Ellis RJ, Gelman BB, Grant I, Letendre SL, Marra CM, Morgello S, Simpson DM, McArthur JC, for the CHARTER Group|
|Abstract:BACKGROUND: Detectable cerebrospinal (CSF) HIV ribonucleic acid (RNA) is associated with central nervous system (CNS) complications, including neurocognitive impairment and depression. Routine monitoring of CSF HIV RNA presents a valuable key to reducing HIV CNS complications. However lumbar puncture procedures pose resource utilization challenges. We developed a prediction model to estimate the risk of detectable CSF HIV RNA (threshold >50copies/ml) that will help identify patients who might benefit most from CSF monitoring.
METHODS: The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) prospective cohort is an ongoing 6-Center, US-based study. We evaluated 811 participants on combination antiretroviral therapy (cART) who underwent CSF evaluation at study entry (2004-2007). We applied points to the final multivariable logistic regression prediction model to develop a detectable CSF HIV Risk Score
RESULTS: Plasma HIV RNA, CNS Penetration Effectiveness (CPE 2.0), duration of cART, adherence, race and depression were retained predictors of CSF HIV RNA (Table 1). The CSF HIV Risk Score ranges from 0 to 42 points and displays good calibration, Hosmer-Lemeshow P-value=0·85, and discrimination, c-statistic=0·90. The distribution of risk scores in our sample ranged from 0 to 39 points, with mean [standard deviation (SD)] of 15.4 (7.3). Figure 2 displays predicted probabilities of detectable CSF HIV RNA at various CSF HIV Risk Scores. For example a Black patient (3 points), with plasma HIV RNA of 300 copies/mL (10 points), who is presently depressed (4 points), and is fully adherent to cART regimen (0 points), with total CPE score of 9 (6 points), for a duration of 10 months (4 points; total CSF HIV Risk Score =27 points), has a 54.3% (95% CI: 46.5-62.0) probability of detecting CSF HIV RNA. For each point increase, the odds of detecting CSF HIV RNA increase by 26% [Odds Ratio (OR)=1.26, 95%CI 1.21-1.31; P<0.01].
CONCLUSION: The CSF HIV Risk Score predicts detection of HIV RNA in the CSF. An elevated risk score suggests which patients will benefit from CSF monitoring. It presents an advance in HIV management and monitoring of CNS effects of HIV, and provides a potentially useful tool for clinicians.|