Neurologic and psychiatric complications of antiretroviral agents.

Advances in highly active antiretroviral therapy (HAART) aim to improve the efficacy of HIV drugs as well as the quality of life in HIV-infected patients. Neurologic and psychologic disturbances that occur because of HIV disease and therapy are of great concern, and because they can overlap and are often difficult to distinguish, their pathogenesis is not clearly understood. Furthermore, these complications can lead to decreased adherence, thereby interfering with treatment outcomes. Antiretrovirals, including nonnucleoside reverse transcriptase inhibitors, can penetrate the central nervous system (CNS) and suppress viral replication, but they can also exacerbate CNS side effects and neuropsychiatric symptoms. When deciding which HAART drug combination is most appropriate for a patient, clinicians must consider the individual's risk of CNS complications together with the efficacy of the specific HAART regimen.

Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter?

To identify factors that affect normalization of laboratory measures after treatment for neurosyphilis, 59 subjects with neurosyphilis underwent repeated lumbar punctures and venipunctures after completion of therapy. The median duration of follow-up was 6.9 months. Stepwise Cox regression models were used to determine the influence of clinical and laboratory features on normalization of cerebrospinal fluid (CSF), white blood cells (WBCs), CSF protein concentration, CSF Venereal Disease Research Laboratory (VDRL) reactivity, and serum rapid plasma reagin (RPR) titer. Human immunodeficiency virus (HIV)-infected subjects were 2.5 times less likely to normalize CSF-VDRL reactivity than were HIV-uninfected subjects. HIV-infected subjects with peripheral blood CD4+ T cell counts of < or =200 cells/ mu L were 3.7 times less likely to normalize CSF-VDRL reactivity than were those with CD4+ T cell counts of >200 cells/ mu L. CSF WBC count and serum RPR reactivity were more likely to normalize but CSF-VDRL reactivity was less likely to normalize with higher baseline values. Future studies should address whether more intensive therapy for neurosyphilis is warranted in HIV-infected individuals.

Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features.

OBJECTIVE: To define clinical and laboratory features that identify patients with neurosyphilis. METHODS: Subjects (n=326) with syphilis but no previous neurosyphilis who met 1993 Centers for Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/ microL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result. RESULTS: Sixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer > or =1 : 32 increased the odds of neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)-uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4+ T cell count < or =350 cells/ microL conferred 3.10-fold increased odds of neurosyphilis in HIV-infected subjects. Similar results were obtained when neurosyphilis was more stringently defined as a reactive CSF VDRL test result. CONCLUSION: Serum RPR titer helps predict the likelihood of neurosyphilis. HIV-induced immune impairment may increase the risk of neurosyphilis.

A phase I/II study of nevirapine for pre-exposure prophylaxis of HIV-1 transmission in uninfected subjects at high risk.

OBJECTIVE: To evaluate the safety, tolerability, and trough levels of three pre-exposure prophylaxis regimens of nevirapine among HIV-1-uninfected subjects at high risk for HIV-1 infection. METHODS: A phase I/II trial (HIVHOP 101) in which 33 such uninfected subjects received a 200 mg tablet of nevirapine once weekly (cohort A, n = 12), twice weekly (cohort B, n = 12), or every other day (cohort C, n = 9) for 12 weeks. Clinical signs/symptoms, laboratory parameters, and nevirapine trough levels were assessed at entry and at 1, 2, 4, 6, 9, and 12 weeks, with a follow-up sample at 16 weeks. RESULTS: No subject experienced clinical symptoms attributed to nevirapine, including rash. There were no significant changes in liver enzyme levels from baseline to week 12 in the three cohorts, except for glutamyl transpeptidase in cohort B. Median nevirapine trough levels at weeks 1 and 12 were 119 ng/ml (range, < 25-205) and 135 ng/ml (range, < 25-1065), respectively, for cohort A, 569 ng/ml (range, 135-2641) and 431 ng/ml (range, 42-2454) for cohort B, and 1942 ng/ml (range, 1214-2482) and 943 ng/ml (range, 262-5281) for cohort C. No subject became HIV-1 antibody positive by week 16. CONCLUSIONS: A single dose of nevirapine taken once weekly, twice weekly, or every other day for 12 weeks was safely tolerated by the subjects in this small study, and resulted in nevirapine levels well above the IC (inhibitory concentration of 50%: 10 ng/ml) over the 12-week period in nearly all evaluable subjects. (50)