Neuroelectric assessment of HIV: EEG, ERP, and viral load.

The effects of the human immunodeficiency virus (HIV) infection on the central nervous system function were studied with electroencephalographic (EEG) and auditory event-related brain potentials (EPRs) in patients infected with HIV and unaffected young adult control subjects (n=10/group). All subjects were assessed once every 15 min for four trial blocks at the same time of day to assess EEG/ERP changes with time on task-induced fatigue. Spectral analysis was applied to the pre- and post-stimulus EEG segments. ERP values were evaluated with respect to group differences for component amplitude and latency measures. Spectral analysis demonstrated that HIV patients evinced greater pre-stimulus delta power over frontal areas compared to control subjects, and less post-stimulus spectral power for the delta, theta, and alpha bands over the central/parietal areas. P300 amplitude was smaller, and latency was marginally longer for the HIV patients compared to control subjects. P300 latency correlated positively with increases in the patient HIV viral load. Time-on-task generally did not affect EEG or ERP measures for either group other than contributing to an overall decrease in neuroelectric responsivity. Group spectral power effects were consistent with differences in arousal/fatigue level. P300 group differences were consistent with declines in cognitive capability, and P300 latency increased with increased viral load. HIV infection negatively affected central nervous system function as measured by EEG and cognitive ERPs in a manner that suggests decreased arousal and increased fatigue in HIV patients.

Nonselective and selective benzodiazepine receptor agonists--where are we today?

Insomnia is problematic for many individuals, causing them to seek treatment. There is a long history of therapies aimed at restoring normal sleep patterns, each having its advantages and disadvantages. This review traces the history of insomnia drug therapies from chloral hydrate and the barbiturates through the benzodiazepines and explores the newest selective benzodiazepine receptor agonists, including zolpidem and zaleplon. The mechanisms of action of the benzodiazepine receptor agonists are compared and contrasted. A pharmacokinetic comparison is presented showing the importance that parameters such as dose, onset of action, lipophilicity, metabolites, half-life, and receptor-binding affinity have on clinical effects. The possible adverse effects of sleep aids are discussed, including residual sedation and psychomotor impairment, daytime anxiety, anterograde amnesia and cognitive impairment, rebound insomnia, and drug tolerance and dependence. Effects on sleep efficiency and staging are also discussed. Recommendations for the primary care physician on the selection of hypnotics are also provided. Benzodiazepine receptor agonists are often appropriate agents in the treatment of insomnia; however, individual drug and patient considerations are important in matching the most appropriate agent to the individual patient. Zolpidem and zaleplon, newer selective benzodiazepine receptor agonists, offer additional treatment options.

Subjective sleepiness ratings (Epworth sleepiness scale) do not reflect the same parameter of sleepiness as objective sleepiness (maintenance of wakefulness test) in patients with narcolepsy.

OBJECTIVE: To evaluate whether subjective (Epworth Sleepiness Scale or ESS) and objective (Maintenance of Wakefulness Test or MWT) tests of sleepiness are equally useful in patients with narcolepsy. METHODS: Correlational study evaluating the relationship between ESS and MWT as measures of sleepiness. SETTING: Multi-center. PATIENTS: 522 patients (17-68 year old men and women) with a current diagnosis of narcolepsy. INTERVENTIONS: None. RESULTS: Correlations were: MSLT and MWT, r = 0.52 (P<0.001); MWT and ESS, r = -0.29 (P<0.001); MSLT and ESS, r = -0.27 (P<0.001). Regression curve estimation using linear and curvilinear models revealed no difference among linear and curvilinear models between MWT and MSLT, and between MSLT and ESS. However, curvilinear models were better at explaining the relationship between MWT and ESS, with the cubic model being the best. As the level of severe sleepiness (as measured by the MWT) changed, the ESS remained stable. CONCLUSIONS: In a large narcolepsy sample, the MWT and ESS are not equally useful, and do not measure the same parameter of sleepiness.

Sleep latency on the maintenance of wakefulness test (MWT) for 530 patients with narcolepsy while free of psychoactive drugs.

OBJECTIVES: To compare maintenance of wakefulness test (MWT) data gathered at baseline in the course of two, multicenter studies on the therapeutic efficacy of modafinil with published MWT norms. METHODS: The MWT is a procedure that uses electrophysiological measures to determine the ability to remain awake while sitting in a quiet, darkened room. The test consists of 4 20 min trials conducted 4 times at 2 h intervals commencing 2 h after awakening from a night of sleep. MWT data were gathered at baseline in the course of two, multicenter studies on the therapeutic efficacy of modafinil. Subjects were 17-68 year old men (n = 239) and women (n = 291) diagnosed with narcolepsy according to the International Classification of Sleep Disorders (ICSD). All patients were free of psychoactive medication for a minimum of 14 days. RESULTS: Mean MWT sleep latency was 6.0 +/- 4.8 min. However, the mean for the first MWT trial was 7.0 min which was longer that the means for the following 3 trials (5.8, 5.6 and 5.7 min, respectively). The 4 distributions of the individual MWT trials were similar and adequately summarized by the distribution of the average MWT sleep latency. As a group, patients with narcolepsy were less able to remain awake than normals; only 8 of 530 (1.5%) patients were able to remain awake on 4 20 min MWT trials compared with 35 of 64 (54.7%) normals in another study. However, using a mean MWT sleep latency of 12 min (the 5th percentile for normals) as the lowest cut-point for normalcy, 15% of patients with narcolepsy appeared to have an unimpaired ability to remain awake. CONCLUSIONS: The diagnosis of narcolepsy did not always predict inability to remain awake on the MWT. Age, gender and the duration of illness did not predict ability to remain awake. Patients with severe cataplexy and other ancillary symptoms were least able to remain awake on MWT trials. Patients who used tobacco and caffeine moderately had the lowest MWT sleep latencies relative to patients with heavy and light use.

Growth hormone, fatigue, poor sleep, and disability in HIV infection.

Poor sleep, daytime fatigue, and loss of cognitive ability exist during all stages of HIV infection, worsening with disease progression. These symptoms contribute to disability and poor quality of life. Data from several research groups support a role of somnogenic inflammatory process peptides elevated in HIV infection, e.g. TNF alpha. Though the literature is in conflict regarding an effect of HIV infection on growth hormone (GH) secretion, GH axis dysregulation and treatment with GH may be important in HIV infection, e.g. in the wasting syndrome. It has long been known that GH varies with changes in sleep. The hypothesis tested in the current study was that the relationship between delta frequency (0.5-4.0 Hz) sleep EEG amplitude (square root of power from frequency analysis) and GH secretion would differ between HIV positive (HIV+) and HIV negative (HIV-) subjects. In 14 subjects (6 HIV+ and 8 HIV-, none with current or past AIDS-defining illness) a linear relationship change across the night's sleep was found in the coupling between delta frequency sleep EEG amplitude and GH secretion. The phase coupling change was in opposite directions in HIV+ versus HIV- subjects. This difference supports the hypothesis that the brain-based coordination of sleep and sleep-related physiology deteriorates early in HIV infection, and that GH dysregulation may contribute to this sleep pathology.

A normative study of the maintenance of wakefulness test (MWT).

The maintenance of wakefulness test (MWT) is a daytime polysomnographic procedure which quantifies wake tendency by measuring the ability to remain awake during soporific circumstances. We present normative data based on 64 healthy subjects (27 males and 37 females) who adhered to uniform MWT procedural conditions including polysomnographic montage, illuminance level, seating position, room temperature, meal timing, and subject instructions. When allowed a maximum trial duration of 40 min, subjects' mean sleep latency to the first epoch of sustained sleep was 35.2 +/- 7.9 min. The lower normal limit, defined as two standard deviations below the mean, was 19.4 min. Calculation of data on the basis of a maximum trial duration of 20 min and sleep latency to the first appearance of brief sleep (a microsleep episode or one epoch of any stage of sleep) yielded a mean sleep latency of 18.1 +/- 3.6 min and a lower normal limit of 10.9 min. Sleep latency scores were significantly higher than those previously reported in patients with disorders of excessive somnolence. Therefore, the MWT appears to be a useful procedure in differentiating groups with normal daytime wake tendency from those with impaired wake tendency and in identifying individuals with pathologic inability to remain awake under soporific circumstances.

The sleep of long-haul truck drivers.

BACKGROUND: Fatigue and sleep deprivation are important safety issues for long-haul truck drivers. METHODS: We conducted round-the-clock electrophysiologic and performance monitoring of four groups of 20 male truck drivers who were carrying revenue-producing loads. We compared four driving schedules, two in the United States (five 10-hour trips of day driving beginning about the same time each day or of night driving beginning about 2 hours earlier each day) and two in Canada (four 13-hour trips of late-night-to-morning driving beginning at about the same time each evening or of afternoon-to-night driving beginning 1 hour later each day). RESULTS: Drivers averaged 5.18 hours in bed per. day and 4.78 hours of electrophysiologically verified sleep per day over the five-day study (range, 3.83 hours of sleep for those on the steady 13-hour night schedule to 5.38 hours of sleep for those on the steady 10-hour day schedule). These values compared with a mean (+/-SD) self-reported ideal amount of sleep of 7.1+/-1 hours a day. For 35 drivers (44 percent), naps augmented the sleep obtained by an average of 0.45+/-0.31 hour. No crashes or other vehicle mishaps occurred. Two drivers had undiagnosed sleep apnea, as detected by polysomnography. Two other drivers had one episode each of stage 1 sleep while driving, as detected by electroencephalography. Forty-five drivers (56 percent) had at least 1 six-minute interval of drowsiness while driving, as judged by analysis of video recordings of their faces; 1067 of the 1989 six-minute segments (54 percent) showing drowsy drivers involved just eight drivers. CONCLUSIONS: Long-haul truck drivers in this study obtained less sleep than is required for alertness on the job. The greatest vulnerability to sleep or sleep-like states is in the late night and early morning.

Sleep latency measures of caffeine effects during sleep deprivation.

Studies of stimulants during sleep deprivation have used performance assessment batteries (PABs) and occasionally the multiple sleep latency test (MSLT) as measures. Another type of sleep latency test, the maintenance of wakefulness test (MWT), assesses ability to remain awake without assistance, rather than ability to go to sleep. The MWT previously has not been used in studies of stimulants during sleep deprivation. This study of caffeine during 64 h without sleep included a PAB, the MSLT, and a single MWT trial per day. The PAB and the MSLT were sensitive to caffeine effects during the first 24 h without sleep. The MWT demonstrated that caffeine improved ability to remain awake even after 2 nights of sleep deprivation. Ability to go to sleep and ability to stay awake during sleep deprivation appear to be affected differently by caffeine. PAB testing may fail to detect this stimulant effect because technicians prevent subjects from nodding off during PAB testing, an external support not available to subjects during the MWT and also not available in many real-world work environments. The MWT was more sensitive to stimulant amelioration of sleep-deprivation effects. The findings need to be validated with MWTs at other times of day and with other stimulants.

Effect of bedtime alcohol on inspiratory resistance and respiratory drive in snoring and nonsnoring men.

We measured inspiratory resistance (R1), inspiratory occlusion pressure (P0.1), and the ventilatory responses to hypercapnia and isocapnic hypoxia during waking and during stage 2 non-rapid eye movement sleep in nine young men who were habitual snorers. They were studied on 2 nights during the 3 hours after receiving a bedtime drink containing either a placebo or 100-proof vodka (1.5 ml/kg) in orange juice. We compared the results with those we reported previously in 10 nonsnoring but otherwise similar men. Waking R1 was the same in nonsnorers and snorers, and it was not affected by ethanol. During sleep on the control night, R1 increased by 70% in nonsnorers and by 280% in snorers. On the ethanol night, the increase from waking to sleeping was more than doubled in both nonsnorers and snorers. P0.1 and the responses to hypercapnia and hypoxia showed no differences between nonsnorers and snorers, therefore the results from the two groups were pooled. Minute ventilation and the hypercapnic response decreased from waking to sleeping and P0.1 was more negative during sleep, but there was no significant effect of ethanol. There was a significant correlation between the changes from waking to sleeping in R1 and P0.1 on the ethanol night suggesting that inspiratory effort increased in response to the increased resistance. The response to isocapnic hypoxia showed no effect of either sleep state or drink. Inspiratory time did not change but mean inspiratory flow (VT/T1) was significantly reduced during sleep on both control and ethanol nights. The duty cycle ratio (T1/Ttot) was significantly increased during sleep on the ethanol night. Despite its great effect on inspiratory resistance, especially in snorers, ethanol, in the dose used in our study, does not augment the depression of minute ventilation or of the hypercapnic response that occur normally in stage 2 non-rapid eye movement sleep. After ethanol, our subjects showed the decreased VT/T1 and the increased T1/Ttot that occur normally during sleep in response to an inspiratory resistive load. However, they also showed increased inspiratory effort. The combination of increased inspiratory resistance and greater inspiratory effort would increase the tendency of an unstable upper airway to collapse and could account for the aggravation of obstructive sleep apnea by ethanol.

HLA haplotypes, polysomnography, and pedigrees in a case series of patients with narcolepsy.

An ongoing study of the genetics of narcolepsy ascertains families through a case series of narcoleptic probands using diagnostic criteria consisting of 1) clinical history of excessive somnolence, 2) a mean sleep latency on the multiple sleep latency test (MSLT) of less than 7.9 minutes, 3) the rapid eye movement (REM) sleep-related symptom of cataplexy, 4) nocturnal polysomnography ruling out sleep apnea syndrome, and 5) two or more transitions to REM sleep on the MSLT. All probands and first-degree relatives received clinical and laboratory evaluations as well as human leukocyte antigen (HLA) typing. Demographic characteristics of the 32 probands are as follows: 17 males and 15 females; mean age was 42.1 years (range 13-70 years). The polysomnographic data confirmed daytime sleepiness and increased tendency for REM sleep for the 32 probands. Nocturnal polysomnographic results are as follows: sleep latency, 3.2 minutes; total sleep time, 442 minutes. MSLT results are as follows: sleep latency, 3.1 minutes; REM latency, 6.9 minutes; number of REM periods, 3.2. HLA typing revealed the presence of the HLA haplotypes, DRB1*15 and DQB1*0602, in 21 narcoleptic probands, with two African-Americans having the DQB1*0602 but not the DRB1*15 allele. Among the 57 relatives of the 32 probands, 1/31 females and 7/26 males were found to be affected with narcolepsy (p < 0.02), which suggests a higher diagnostic rate in male relatives. The 21 probands who were positive for the DRB1*15 and DQB1*0602 haplotypes did not differ from the 10 probands who were negative for these alleles in terms of their nocturnal sleep parameters, MSLT findings, or clinical presentation. Three families with multiple individuals affected with narcolepsy are presented. Two families have more than one affected individual who does not have the high-risk HLA haplotype. In one of these families, the disease is segregating independently of any HLA haplotype. In the third family, there is cosegregation with HLA DRB1*15 and DQB1*0602. One family contains a pair of DNA-confirmed, monozygotic twins with narcolepsy who are discordant for cataplexy and have the HLA DR14(Dw9)/DQB1*0503 and DR4(Dw4)/DQB1*0302 haplotypes.

The mandibular repositioning device: role in the treatment of obstructive sleep apnea.

The role of oral appliances in the routine treatment of obstructive sleep apnea (OSA) is not well defined. This prospective study attempts to clarify the clinical role of a specific oral appliance, the mandibular repositioning device (MRD). This study evaluated the demographic, polysomnographic, and cephalometric radiographic findings predictive of treatment success or failure with the MRD. Twenty-nine patients were diagnosed with mild to severe OSA by nocturnal polysomnography. The majority of these patients were intolerant to nasal continuous positive airway pressure (CPAP) and all were fitted with a MRD. Twenty-three of these patients were compliant initially with MRD use and received post-treatment nocturnal polysomnogrpahy at a mean of 104 days after receiving the device. The respiratory disturbance index (RDI) decreased with MRD use (37 +/- 23 versus 18 +/- 20 events/hour, p < 0.001), and 16 of the 23 patients (69%) were considered responders (decrease in RDI > or = 50% and posttreatment RDI < or = 20). Measurements of subjective and objective daytime sleepiness, nocturnal oxygen desaturation, and snoring were all improved with MRD use. A pre-treatment RDI > 40 was present in four of the seven (67%) non-responders. Age, body mass index, and cephalometric radiographic measurements were not predictive of treatment outcome. Sixteen of 23 patients (70%) continue to use the MRD after 3.4 +/- 0.7 years. This study suggests that the MRD is useful in the long-term treatment of patients with OSA of mild to moderate severity.

Sleepiness and human behavior.

The 24-hour properties of sleepiness affect behavior by reducing performance and increasing the likelihood of accidents. This is important to pulmonary physicians who diagnose and treat sleep apnea, because diagnoses of sleep apnea and narcolepsy are associated with as much as a sevenfold increase in the risk of having a motor vehicle accident. Human abilities throughout the 24-hour day have noticeable ups and downs and are probably causally linked to the same control mechanisms that produce the early morning and midafternoon peaks in the tendency to fall asleep. An important characteristic of this pattern is that increased sleep tendency, regardless of how the increase comes about, does not alter the timing of the peaks. In California, and perhaps other states, current laws can be interpreted as requiring clinicians to report all patients with conditions such as sleep apnea and narcolepsy to the county health officer. Although this policy is at variance with recommendations of the American Thoracic Society, attorneys have advised that, in California, a policy of uniformly reporting all patients with disorders of excessive somnolence is proper. Because ignorance of the law is not a valid defense, it is important for physicians to be aware of all state laws relevant to their patients who may be impaired by sleepiness.

Effects of low energy emission therapy in chronic psychophysiological insomnia.

The treatment of chronic psychophysiological insomnia presents a challenge that has not been met using currently available pharmacotherapy. Low energy emission therapy (LEET) has been developed as a potential alternative therapy for this disorder. LEET consists of amplitude-modulated electromagnetic fields delivered intrabuccally by means of an electrically conducting mouthpiece in direct contact with the oral mucosa. The effect of LEET on chronic psychophysiological insomnia was assessed with polysomnography (PSG) and sleep rating forms on a total of 106 patients at two different centers. Active or inactive LEET was administered for 20 minutes in late afternoon three times a week for a total of 12 treatments. Primary efficacy endpoints evaluating the results were changes from baseline in PSG-assessed total sleep time (TST) and sleep latency (SL). Secondary endpoints were changes in sleep efficiency (SE), sleep stages, and reports by the subjects of SL and TST. There was a significant increase in TST as assessed by PSG between baseline and post-treatment values for the active treatment group (76.0 +/- 11.1 minutes, p = 0.0001). The increase for the inactive treatment group was not statistically significant. The TST improvement was significantly greater for the active group when compared to the inactive group (adjusted for baseline TST; p = 0.020. R1 = 0.20). There was a significant decrease in SL as assessed by PSG between baseline and post-treatment values for the active treatment group (-21.6 +/- 5.9 minutes, p = 0.0006), whereas the decrease noted for the inactive treatment group was not statistically significant. The difference in SL decrease between the two treatment groups was marginally significant (adjusted for baseline SL and center, p = 0.068, R2 = 0.60). The number of sleep cycles per night increased by 30% after active treatment (p = 0.0001) but was unchanged following inactive treatment. Subjects did not experience rebound insomnia, and there were no significant side effects. The data presented in this report indicate that LEET administered for 20 minutes three times a week increased TST and reduced SL in chronic psychophysiological insomnia. LEET is safe and well tolerated and it effectively improved the sleep of chronic insomniacs given 12 treatments over a 4-week period by increasing the number of sleep cycles without altering the percentage of the various sleep stages during the night. The therapeutic action of LEET differs from that of currently available drug therapies in that the sleep pattern noted in insomniacs following LEET treatment more closely resembles nocturnal physiological sleep. This novel treatment may offer an attractive alternative therapy for chronic insomnia.

Self-reported snoring in pregnancy. Association with fetal outcome.

OBJECTIVES: To determine the incidence of self-reported snoring in pregnant compared with nonpregnant women. To compare indicators of fetal outcome in pregnant women with self-reported frequent snoring vs those without snoring. STUDY DESIGN: Prospective, nonrandomized screening and comparison between groups. PATIENTS: Three hundred fifty pregnant women and 110 age-matched nonpregnant women. METHODS: Survey evaluating self-reported snoring. For the pregnant women, infant birthweight, APGAR scores, and other indicators of fetal outcome were obtained by record review. RESULTS: Frequent snoring was reported in 14% of the pregnant women vs 4% of the nonpregnant women (Chi2=6.2; df=1; p<0.05). The pregnant women who reported frequent snoring did not have deliveries resulting in infants with evidence of an increase in compromised outcomes. CONCLUSIONS: Frequent snoring is reported more often in pregnant than in nonpregnant women. Snoring mothers do not appear to be at increased risk for delivering infants with fetal compromise as might be expected with the concomitant occurrence of obstructive sleep apnea.

Methods of testing for sleepiness [corrected].

Normal nonrandom fluctuation in daily human performance have been documented for years. Published research reports have shown patterns of workers' errors in reading gas meters, operators' delays in answering calls, drivers' drowsiness, sleepy locomotive engineers' automatic breaking, vehicle crashes, deaths resulting from disease, brief periods of sleep, and sleep latency in structured naps. The authors summarized these data sets and fitted them with a two-peak-per-day cosine curve derived from the population growth function used in chaos theory. Median parameters extracted from the curve fits predicted a sharp peak of sleepiness at 2:30 AM and a secondary peak at 2:30 PM. The shape of the curve was modified by a nonlinear sleep-deprivation factor. The model appeared to be biological rather than behavioral or social because it applied well to disease-related deaths. The authors also review measurement of sleepiness through electroencephalographic monitoring, self-reports, pupillography, and the Multiple Sleep Latency and the Maintenance of Wakefulness Tests.

Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection.

We tested the hypothesis that increases in tumor necrosis factor alpha (TNF-alpha) induced by human immunodeficiency virus (HIV) are associated with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infection. Nocturnal sleep disturbances and associated fatigue contribute to the disability of HIV infection. TNF-alpha causes fatigue in clinical use and promotes slow-wave sleep in animal models. With slow progress toward a vaccine and weak effects from current therapies, efforts are directed toward extending productive life of HIV-infected individuals and shortening the duration of disability in terminal illness. We describe previously unrecognized nocturnal cyclic variations in plasma levels of TNF-alpha in all subjects. In 6 of 10 subjects (1 control subject, 3 HIV-seropositive patients with CD4+ cell number > 400 cells per microliters, and 2 HIV-positive patients with CD4+ cell number < 400 cells per microliters), these fluctuations in TNF-alpha were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4+ cell number < 400 cells per microliters and 1 control subject. In 5 HIV subjects with abnormally low CD4+ cell counts ( < 400 cells per microliters), the number of days since seroconversion correlated significantly with low correlation between TNF-alpha and delta amplitude. We conclude that a previously unrecognized normal, physiological coupling exists between TNF-alpha and delta amplitude during sleep and that the lessened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.

Sleep disturbance in early HIV infection.

AIDS: Immune proteins may have a role in HIV-related sleep disturbance. Observations of two notable sleep changes, increase in slow wave sleep and the need for too much sleep, during early stage HIV infection prompted researchers to investigate the neurological changes occurring with sleep structure alterations. When psychiatric, psychological, medical, and pharmacological variables are excluded, researchers begin to examine the effect of HIV infection on the brain itself. While reasons for sleep structure distortion remain unknown, new data suggests that irregular levels of peptides may be involved. Upcoming clinical trials will evaluate medications for efficacy in treating HIV-related sleep disturbance. This could lead to therapies that restore sleep and improve quality of life.^ieng

Early central nervous system response to HIV infection: sleep distortion and cognitive-motor decrements.

OBJECTIVE: To repeat and extend findings suggesting that sleep disturbance, excessive daytime sleepiness, and degraded cognitive-motor abilities may be early markers of central nervous system (CNS) involvement in HIV infection. DESIGN: A controlled, cross-sectional, prospective analysis. SETTING: Clinical research center at a teaching hospital and a military health research center. SUBJECTS: Twenty-three HIV-positive (mean CD4+ count, 387 +/- 162 x 10(6)/l) and 13 seronegative men who were Naval personnel or participants of the University of California, San Diego HIV Neurobehavioral Research Center. MAIN OUTCOME MEASURES: Nocturnal and daytime sleep electroencephalogram, electromyogram, and electrocardiogram. Simple and complex cognitive-motor performance assessed via computerized tasks. RESULTS: Comparison of sleep parameters based on HIV status, length of time infected, zidovudine use, and CD4+ count indicated that CD4+ T cells > 400 x 10(6)/l were associated with a distortion in nocturnal sleep characterized by increased stages 3 and 4 non-rapid eye movement (i.e., slow-wave) sleep in the latter portion of the night and reduced nocturnal awakenings. HIV-positive patients were no sleepier in the daytime than controls. Cognitive-motor performance revealed deficits in both accuracy and efficiency for HIV-positive patients. CONCLUSION: Asymptomatic HIV-positive patients with CD4+ counts > 400 x 10(6)/l demonstrate a statistically significant increase in slow-wave sleep during the latter portion of the night and less arousability. CD4+ lymphocyte count in the early phases of HIV infection appears to differentiate between various levels of HIV disease progression with respect to certain CNS measurements of nocturnal sleep and cognitive-motor performance. Sleep structure distortion remains one of the earliest and most consistently replicable physiological signs of HIV infection. This distortion may provide a link to immune function, disease progression, and cognitive-motor disability in HIV infection.