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Thomas D. Marcotte, PhD; Reena Deutsch, PhD; J. Allen McCutchan, MD; David J. Moore, MS; Scott Letendre, MD; Ronald J. Ellis, MD, PhD; Mark R. Wallace, MD; Robert K. Heaton, PhD; Igor Grant, MD

Arch Neurol. 2003;60:1406-1412.

Background  Neuropsychological (NP) impairment is a relatively common sequela in human immunodeficiency virus (HIV)–infected individuals with advanced disease. Early antecedents of NP dysfunction, however, remain poorly understood.

Objective  To determine whether early markers of immunocompetence and viral replication in individuals who have undergone seroconversion would be of prognostic value in identifying subjects who would become cognitively impaired.

Methods  Seventy-four subjects with estimable seroconversion dates and normal cognition at baseline (a median of 1 year after seroconversion) received NP and laboratory evaluations, including reverse transcription–polymerase chain reaction measurements of plasma (N = 74) and cerebrospinal fluid (n = 47) levels of HIV RNA. Subjects were followed up longitudinally, and were considered to have reached the end point if they became cognitively impaired.

Results  Using Kaplan-Meier estimates, the subgroups with the most rapid progression to NP impairment were (1) subjects with early reductions in CD4 counts (<400 cells/µL at baseline; P = .007) and (2) those with elevated plasma HIV RNA values (>4.5 log₁₀ copies/mL; P = .03) early after seroconversion. Using proportional hazards modeling, the highest-risk subjects had both CD4 counts less than 400 cells/µL and HIV RNA levels greater than 4.5 log₁₀ copies/mL (risk ratio, 6.0; P = .01). In most subjects (7/9 [78%]), NP impairment developed before an acquired immunodeficiency syndrome–defining illness.

Conclusions  Neurocognitive outcomes in HIV are strongly influenced by very early systemic virological and immunological events. Patients with high plasma levels of HIV RNA and low CD4 counts early after infection should be aggressively treated to prevent immunological decline and NP deterioration.

San Diego HIV Neurobehavioral Research Center (HNRC) Group

From the Departments of Psychiatry (Drs Marcotte, Heaton, and Grant and Mr Moore), Family and Preventive Medicine (Dr Deutsch), Medicine (Drs McCutchan and Letendre), and Neurosciences (Dr Ellis), University of California–San Diego, the United States Naval Medical Center–San Diego (Dr Wallace), and the Psychiatry Service, San Diego Veterans Affairs Healthcare System (Dr Grant), San Diego, Calif.

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