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and Hepatitis.com Coverage of the
17th Conference on Retroviruses and
Opportunistic Infections (CROI 2010)
February 16 - 19, San Franciso, California
Risk Factors for Neurocognitive Impairment among People with HIV
CSF Viral Load
Scott Letendre and colleagues (abstract 172) presented the latest data from CHARTER (CNS HIV Antiretroviral Therapy Effects Research), an ongoing multi-center observational study of neurocognitive function in people with HIV.
In a cross-sectional analysis of 1221 participants, the researchers measured HIV viral load in the cerebrospinal fluid (CSF) surrounding the brain and spinal cord, using an assay with a lower limit of quantitation of 50 copies/mL.
About three-quarters of the participants were men, the median age was 43 years, about two-thirds were on ART and the rest were treatment-naive. The median CD4 count was about 415 cells/mm3, but the nadir (lowest-ever) level was 175 cells/mm3 and about 60% had a prior AIDS diagnosis.
The median CSF viral load was 50 copies/mL, with 34% of test values showing detectable HIV RNA above this level. CSF viral load was strongly influenced by ART: 76% of 379 untreated patients had detectable CSF viral load, compared with 16% of 842 people on ART. Furthermore, 13% of untreated patients had CSF viral load equal to or higher than plasma viral load.
In a multivariate analysis of untreated patients, higher CSF viral load was associated with higher blood plasma viral load and older age. Among patients on ART, detectable CSF viral load was significantly associated with higher blood viral load, white race/ethnicity, poor ART adherence, and lower CPE score, a measure of how well an individual's antiretroviral drugs penetrate the protective blood-brain barrier.
participants with a regimen CPE score of 3 or lower, 39% had detectable
CSF viral load, compared to 18% of those with a score of 6, and 15%
of those with a score of 9 or higher. Overall, higher CSF viral load
did not predict worse neurocognitive performance, but people with CSF
viral load equal to or exceeding plasma viral load showed impairment.
Ellis and colleagues (abstract 429) also presented data from
the CHARTER cohort. This retrospective analysis included 1526 participants;
demographic and HIV-related characteristics were similar to those described
above, though a larger proportion (about 70%) were on ART.
People with lower nadir CD4 cell levels had a higher likelihood of neurocognitive impairment, while those whose CD4 count never fell below 350 cells/mm3 were at lower risk (odds ratio 0.62 vs CD4 nadir < 50 cells/mm3). The same association was seen in an analysis restricted to people with HIV RNA < 50 copies/mL.
Nadir CD4 count was the only significant predictor of cognitive impairment, and it remained so after adjusting for potential confounding factors including plasma viral load, age, sex, race/ethnicity, and duration of HIV infection. Current CD4 cell count, in contrast, was not significantly associated with impaired neurocognitive function.
These findings underline the benefits of earlier ART initiation in reducing the risk of neurocognitive impairment. Preventing impairment is important, the researchers noted, since once HAND occurs, many individuals remain impaired despite effective viral suppression on ART.
interruption arm was discontinued ahead of schedule in January 2006
after a preliminary analysis showed that participants in that group
had higher rates of death and both AIDS-defining opportunistic illness
and non-AIDS conditions including cardiovascular, liver, and kidney
Abstract 429: Univ of California, San Diego, CA; Washington Univ, St Louis, MO; Univ of Texas Med Branch, Galveston, TX; Mt Sinai Sch of Med, New York, NY.
Abstract 415: Monash Univ, Alfred Hosp and Burnet Inst, Melbourne, Australia; Univ of Minnesota, Minneapolis, MN; Univ of North Carolina at Chapel Hill, NC; St Vincent's Hosp and Univ of New South Wales, Sydney, Australia; Natl Ctr in HIV Epi and Clin Res, Univ of New South Wales, Sydney, Australia; JICA-NIH Project, Ministry of Publ Hlth, Thailand; Denver Public Health, Denver, CO; Inst de Infectologia Emilio Ribas, Sao Paulo, Brazil; Univ of California, San Francisco, CA.
S Letendre, C FitzSimons, R Ellis, and others (CHARTER Group). Correlates of CSF Viral Loads in 1221 Volunteers of the CHARTER Cohort. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 172.
R Heaton, S Letendre, and others (CHARTER Group). Higher CD4 Nadir Is
Associated with Reduced Rates of HIV-associated Neurocognitive Disorders
in the CHARTER Study: Potential Implications for Early Treatment Initiation.
17th Conference on Retroviruses & Opportunistic Infections (CROI
2010). San Francisco. February 16-19, 2010. Abstract