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Worse Neuropsych Scores Tied to
Viral Rebounds in CSF and Plasma; CPE Score Tied to CSF Rebound
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
Worse neuropsychological performance determined by standard tests presaged viral rebounds in cerebrospinal fluid (CSF) and plasma in a longitudinal CHARTER cohort analysis [1]. CHARTER investigators also traced an association between antiretroviral regimens with a worse central nervous system (CNS) penetration effectiveness (CPE) score and faster rebound in CSF, but not in plasma.
CHARTER is a prospective six-site US cohort study. This analysis included people taking antiretrovirals at their first cohort visit, 346 of them with a viral load below 50 copies in CSF and 225 with an undetectable load in plasma. Neuropsychological testing included a battery of tests with demonstrated sensitivity in HIV-associated neurocognitive disorder (HAND).
The CSF and plasma groups were similar in age, averaging around 45 years. Years of education averaged 12.7 to 12.8 years in the CSF and plasma groups, and about 20% in each group were women. Current CD4 count stood at 459 and nadir count at 112 in the CSF group, with respective values of 484 and 133 in the plasma group.
Antiretroviral therapy duration averaged 11.1 years in the CSF contingent and 12.5 years in the plasma group, and just over 90% in each group reported better than 95% antiretroviral adherence. While one third in the CSF cluster had a detectable viral load in plasma, none (by definition) in the plasma group had detectable virus in plasma. CPE scores based on the 2010 ranking averaged 7.4 in the CSF group and 7.5 in the plasma group.
Among the 346 people with an initial CSF load under 50 copies, 67 (19%) had a rebound in CSF over a median 9.3 months of follow-up. A multivariate model identified nine factors that predicted shorter time to viral rebound in CSF:
· CD4 count below 200
· Age 44 or younger
· Black ethnicity
· Neuropsychological global rating at or above 4
· Protease inhibitor regimen versus nonnucleoside regimen
· CPE score x age (under 8 x 44 or younger)
· Ethnicity x neuropsychological global rating: black x 4 or greater
· Plasma viral load above 50 copies
· Nonuse of antidepressants
Through a median 11.0 months of follow-up, 82 people in the plasma group (36%) endured a rebound above 50 copies. Four factors independently predicted shorter time to plasma rebound:
· CD4 count below 200
· Age 44 or younger
· Black ethnicity
· Neuropsychological global rating at or above 4
The CHARTER team believes the relatively high rebound rates in CSF and plasma can be explained by the advanced stage of infection in the study groups (74% had AIDS), the heavy antiretroviral experience (25% had taken eight or more prior antiretrovirals), and the rigorous rebound definition (above 50 copies).
The investigators proposed that the association between a low CPE score and faster time to CSF rebound "reinforce accumulating evidence that antiretrovirals that reach higher concentrations in the nervous system lead to better control of HIV in CSF." However, a 20,000-person UK CHIC cohort study presented at this meeting found that neither the CPE score of a person's first antiretroviral regimen nor the CPE score of the latest regimen predicted the risk of CNS complications during follow-up [2]. (from Jules: as I said earlier an association between CPE score and improved neurologic impairment depends on many factors that may prevent the CPE score from showing benefit. HIV enters the brain shortly after HIV-infection and never leaves causing permanent damage. Nadir CD4 and when starting HAART probably have an affect on trying to reverse imairment. The presence of comorbidities affects impairment, like diabetes, hypertension and CVD, as well as HCV coinfection. Sometimes a high CPE score regimen may not be enough. In addition how the study is conducted appears to matter, what kind of neurologic performance testing that is used may also be relevant to evaluating neurologic impairment).
References
1. Letendre S, Ellis R, Deutsch R, et al. Correlates of time-to-loss-of-viral-response in CSF and plasma in the CHARTER cohort. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 430.
2. Garvey L, Winston A, Sabin C, and the UK CHIC Study Group. Does cART with greater CNS penetration prevent the development of CNS opportunistic diseases? 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 427. http://www.retroconference.org/2010/PDFs/427.pdf.
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