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Background:  Neurocognitive disorders remain common among human immunodeficiency virus (HIV)-positive adults, perhaps owing to persistent HIV-1 RNA in cerebrospinal fluid (CSF) during antiretroviral therapy (ART).Methods:  Using a single-copy assay, we measured HIV-1 RNA levels in CSF and plasma specimens from 220 HIV-positive adults who were taking suppressive ART. Fifty-five participants were tested twice.Results:  HIV-1 RNA was detected in 42.3% of CSF and 65.2% of plasma samples. Correlates of higher CSF HIV-1 RNA levels included higher nadir and current CD4+ T-cell counts, a plasma HIV-1 RNA level of ≥ 1 copy/mL, and a lower central nervous system penetration-effectiveness score (model P < .001). Worse neurocognitive performance was associated with discordance in HIV-1 RNA detection between plasma and CSF, lower overall CSF HIV-1 RNA level, and longer ART duration, among others (model P < .001). In the longitudinal subgroup, CSF HIV-1 RNA persisted in most participants (69%) over 7 months.Conclusions:  Low-level HIV-1 RNA in CSF is common during suppressive ART and is associated with low-level HIV-1 RNA in blood, better immune status, and lower ART drug distribution into CSF. The association between HIV-1 RNA discordance and HIV-associated neurocognitive disorder (HAND) may reflect compartmentalization. The relationship between HAND, lower HIV-1 RNA levels in CSF, and lower CD4+ T-cell counts may reflect disturbances in the immune response to HIV-1 in the CNS. [ABSTRACT FROM AUTHOR]

Background: Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown.Methods: We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4(+) T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments.Results: HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01).Conclusions: Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons. [ABSTRACT FROM AUTHOR]

Patients undergoing bronchoscopy for possible pneumocystis pneumonia were studied retrospectively to characterize the impact of common viral pathogens on the course of advanced human immunodeficiency virus (HIV) disease and atypical pneumonia. In 327 episodes, Pneumocystis carinii was found in 220 (67%), cytomegalovirus (CMV) in 145 (44%), and herpes simplex virus in 16 (5%). Early deterioration in oxygenation and use of intensive care was less common in CMV-positive patients. Neither CMV nor P. carinii was a predictor of mortality in multivariate analyses. CMV was not associated with an increased prevalence of later CMV disease. Isolation of CMV from the bronchoalveolar lavage fluid of these patients was not an indication for antiviral therapy. Pulmonary shedding of CMV may be associated with a decreased inflammatory response to P. carinii. The outcome of HIV-associated atypical pneumonia where no clear pulmonary pathogen is found on routine evaluation was no better than that of treated P. carinii pneumonia. [ABSTRACT FROM AUTHOR]

The in vivo interaction of human cytomegalovirus (HCMV) with leukocytes from a group of immunosuppressed patients was studied using specific subgenomic DNA probes and in situ cyto-hybridization. Study subjects had no recognized disease due to HCMV or had HCMV retinitis or colitis. Viral nucleic acid was detected in lymphocytes, monocytes, and polymorphonuclear leukocytes (PMNL). PMNL were consistently hybridization-positive for HCMV RNA and DNA in patients with HCMV viremia. Monocytes were occasionally positive by hybridization and lymphocytes were rarely positive. These findings demonstrate that the HCMV genome is expressed in PMNL of viremic patients and that PMNL may play an important role in virus dissemination. [ABSTRACT FROM PUBLISHER]

Analysis of 71 strains of Neisseriaceae by starch-gel electrophoresis of hexokinase, phosphoglucomutase, glucose phosphate isomerase, and l-malate-nicotinamide adenine dinucleotide phosphate oxidoreductase showed that all gonococci and all meningococci have a characteristic hexokinase isoenzyme that is specific for each species and clearly distinguishes meningococci and gonococci from each other and from other species of Neisseriaceae. Strains of gonococci that were transformed into maltose utilizers by DNA from Neisseria lactamica and Neisseria meningitidis showed no change in the isoenzymes so that they could still be differentiated from meningococci and other Neisseriaceae by isoenzyme electrophoresis. In view of the limited sensitivity and specificity of conventional tests for the identification of gonococci and the possibility that gonococci may be transformed into maltose utilizers by DNA from normal throat flora, electrophoresis of hexokinase isoenzymes should be useful for the precise laboratory identification of the pathogenic neisseriae, especially those from atypical sites and those giving indeterminate reactions. [ABSTRACT FROM PUBLISHER]

The development of opportunistic infections and the administration of vaccines have been associated with transient increases of human immunodeficiency virus (HIV) RNA plasma levels in HIV-infected patients. To determine the relationship between Mycobacterium avium complex (MAC) bacteremia and HIV RNA levels, HIV RNA levels in patients who developed MAC bacteremia (cases) were compared with levels in patients who remained free of MAC disease (controls). Cases and controls were matched for CD4 cell count, prophylaxis against MAC disease, antiretroviral therapy, and duration of follow-up. Mean baseline HIV RNA levels were 4.8 log10 copies/mL in cases and 4.6 log10 copies/mL in controls (P = 0.22). HIV RNA levels increased by a median of 0.4 log in cases but not controls at the time of MAC bacteremia (P = 0.01). In AIDS patients, the onset of MAC bacteremia is associated with a modest but significant increase in serum HIV RNA levels. Increased HIV replication may contribute to the higher mortality associated with MAC bacteremia. [ABSTRACT FROM PUBLISHER]

Patients with AIDS and Mycobacterium avium complex (MAC) bacteremia are at high risk for relapse and emergence of resistant isolates during monotherapy with clarithromycin. Ninety-five AIDS patients with MAC bacteremia received clarithromycin plus clofazimine, with or without ethambutol, in a prospective, multicenter, randomized open-label trial. Of 80 patients with positive baseline cultures, sterilization or a 2 log10 reduction in colony-forming units of MAC in two consecutive blood cultures occurred in 69% of both groups. There were nine relapses in the two-drug arm and three in the three-drug arm. Kaplan-Meier estimates of risk of relapse at 36 weeks were 68% and 12%, respectively (P = .004). All relapse isolates were resistant to clarithromycin. Median time to clarithromycin resistance was 16 weeks with two drugs and 40 weeks with three drugs (P = .004). Ethambutol reduced relapses and emergence of clarithromycin resistance and should be considered an essential component of clarithromycin-based therapies for MAC bacteremia. [ABSTRACT FROM PUBLISHER]

Eight patients (6, cryptococcal meningitis; 2, high-titer cryptococcal antigenemia) were treated with 800 mg/day fluconazole to assess the safety and efficacy of high-dose fluconazole as primary therapy. Five patients with meningitis had resolution of clinical symptoms and all 6 had negative cerebrospinal fluid (CSF) cultures by day 82 (median, 21 days). One meningitis patient developed neurologic deterioration and was switched to amphotericin B at day 18, but CSF culture was negative on day 15 of fluconazole therapy. In 2 patients with cryptococcal antigenemia, clinical symptoms resolved and serum antigen titers declined rapidly; they did not progress to meningitis. Therapy was well tolerated, with mainly gastrointestinal side effects. Four patients had mild increases in liver enzymes; another had a threefold increase in alkaline phosphatase. Mean steady-state serum level of fluconazole was 45 ± 15 µg/mL, and paired CSF and serum levels were 40 ± 14 and 49 ± 14 µg/mL, respectively. High-dose fluconazole appears safe and effective for cryptococcal disease in AIDS patients. [ABSTRACT FROM PUBLISHER]

As part of a longitudinal study, 265 cerebrospinal fluid (CSF) specimens from 204 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects and 43 seronegative controls were evaluated. Of the 204 seropositive persons, 78 (38%) had > or = 1 CSF culture positive for HIV-1; the probability of being culture positive increased as the number of CSF samples obtained increased (P = .0018). Significantly correlated with culture positivity were elevations in CSF protein level (P = .014) and CSF white blood cell count (P = .001). Virus was more readily cultured from clarified CSF (89%, 42/47) than from the cellular fraction (30%, 14/47; P < .00001). Amplification of HIV-1 DNA by polymerase chain reaction (PCR) from 25 seropositive persons was positive in 9 (82%) of 11 culture-positive and in 4 (29%) of 14 culture-negative specimens, while amplification of viral RNA detected all 11 culture-positive and 9 (64%) of the 14 culture-negative CSF specimens. These data support the hypothesis that the development of HIV-1-associated neurocognitive disorders are not dependent solely on the presence of HIV-1 within the central nervous system. [ABSTRACT FROM AUTHOR]

The inhibition of viremia and p24 core antigenemia in patients infected with human immunodeficiency virus (HIV) was evaluated in separate multicenter, double-blind, placebo-controlled trials of zidovudine and ribavirin. Of 29 patients (14 with AIDS and 15 with AIDS-related complex [ARC]) enrolled in the zidovudine study, 16 received 250 mg of zidovudine every 4 h and 13 received placebo. No difference in HIV isolation from peripheral blood was observed at 20 w in treated versus placebo groups (79% vs. 82%). In patients tolerating zidovudine, mean p24 antigen levels dropped to 8.2% ± 8.1% of their baseline values, whereas in placebo recipients mean p24 antigen levels declined to 61.3% ± 40.8% of their baseline values (P < .005). In the ribavirin study, patients with ARC treated with either 800 mg or 600 mg of ribavirin daily or with placebo showed no consistent reduction in p24 antigenemia or decrease in HIV isolation. These data indicate that decline in p24 antigenemia can be a useful virologic marker in evaluation of new antiretroviral drugs. [ABSTRACT FROM PUBLISHER]

Wehave developed a nucleic acid hybridization assay for detecting human immunodeficiency virus (HIV) RNA in peripheral blood mononuclear cells. This assay can detect HIV RNA in 102 cultured lymphoblastoid cells infected with HIV; it only weakly crossreacts with the RNA of HTLV-I or HTLV-II. For 39 (80%) of 49 seropositive subjects, we detected HIV sequences in the RNA from 106 peripheral blood mononuclear cells. In contrast, we could not detect HIV DNA in samples of DNA from the same number of cells from any of 39 seropositive individuals tested. Three of 33 seronegative individuals had false-positive results. Nevertheless, because wefound an excellent correlation between results from our assay and culture of HIV from peripheral blood mononuclear cells of seropositive subjects, it is unlikely that positive cultures of HIV from these cells reflect latent infection. Nucleic acid hybridization offers a more rapid, simple, and inexpensive alternative to culturefor detecting HIV-infected peripheralblood mononuclear cells. [ABSTRACT FROM PUBLISHER]

Evaluates the need for additional clinical antibiotic trials of a primary or secondary nature for the treatment of atherosclerotic heart disease and to suggest possible designs for future trials. Status of ongoing and already completed clinical trials; Limitations of the trials; Points to consider in planning for further clinical trials.

Examines the cerebrospinal beta chemokine concentration in neurocognitively impaired HIV-1 infection. Influence of beta chemokines in the pathogenesis of HIV infection; Use of multivariate methods in the analysis of dementia status; Identification of immunologic factors in the pathogenesis of HIV infection.