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Biomedical subjects

A C Collier

Publications and source records attributed to A C Collier.

At least 91 records · Page 5Linked to original sources
PubMed1992

Interference of recombinant soluble CD4 immunoglobulin G in flow cytometric measurement of CD4+ lymphocytes.

Recombinant soluble CD4 covalently linked to an immunoglobulin G heavy chain (rCD4-IgG) was evaluated clinically for the treatment of human immunodeficiency virus infection. The interference of rCD4-IgG with the measurement of peripheral blood CD4 lymphocytes by whole-blood lysis flow cytometric analysis was investigated using three commercial monoclonal antibody reagents. Addition of rCD4-IgG resulted in an artifactual decrease in measured CD4 number at rCD4-IgG levels of greater than or equal to 1 micrograms/mL; the threshold for this decrease was dependent on the concentration of monoclonal antibody in the commercial preparation used for the measurement of CD4. This artifactual decrease in CD4 cell count was observed in two patients who received rCD4-IgG intravenously. The apparent decrease in CD4 count was eliminated with the use of a single phosphate-buffered saline wash step before the addition of monoclonal antibody. rCD4-IgG can bind to anti-CD4 antibody and lower the measured CD4 cell count in vitro; this interference can be eliminated by a single or a double wash step and is necessary when using the whole-blood lysis flow cytometric technique of enumerating CD4 lymphocytes in patients receiving rCD4-immunoglobulin G.

Antigens, CD↗
PubMed1992

Central nervous system manifestations in human immunodeficiency virus infection without AIDS.

To characterize neurological and neuropsychological findings associated with human immunodeficiency virus type-I (HIV) infection, 77 seropositive homosexual or bisexual males with no or minor symptoms of HIV were compared prospectively to 44 HIV seronegative men by observers blinded to serological status of the subjects. Neurological symptoms and examination findings were not significantly different between seropositives and seronegatives except for cranial nerve findings, predominantly mild hearing impairment. Mean performance scores for a 15-test neuropsychological battery were within an unimpaired range for both groups, although for five tests, mean scores were significantly poorer in seropositives. After adjustment for vocabulary score, and demographic and psychosocial variables, the mean score of seropositives was significantly worse only for the Benton Visual Retention Test. Magnetic resonance (MR) images of brain were abnormal in 14 (27%) of 52 seropositives and one of 10 seronegatives (value was not significant). HIV was isolated from cerebrospinal fluid (CSF) in 31 (61%) of 51 seropositives. The only clinical or laboratory difference between CSF culture positives and negatives was a higher CSF immunoglobulin synthesis rate in the former subjects (medians of 10.3 versus 0.1 mg/day; p = 0.03). An additional 13 seropositive subjects had immunologic evidence of central nervous system HIV infection, defined by a serum-to-CSF HIV antibody ratio of less than 5.5. Intracranial abnormalities on MR imaging were associated with CSF immunologic responses to HIV. Nervous system involvement occurred in the vast majority of men with early HIV infection, but clinically significant impairment was uncommon.

Adult↗
PubMed1991

Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein.

In a randomised phase I trial of a recombinant vaccina virus vaccine expressing the gp160 envelope gene of the human immunodeficiency virus (HIVAC-1e) 35 healthy, HIV-seronegative males, 31 of whom had a history of smallpox immunisation and 4 of whom were vaccinia naive, were vaccinated and then boosted 8 weeks later with HIVAC-1e or standard NY strain vaccinia virus. The frequency, duration, and titre of virus isolation from the vaccination site and occurrence of local side-effects were similar between the two groups of vaccinees. Vaccinia-naive (vac-n) subjects shed virus from the vaccination site for longer and at a higher titre than did vaccinia-primed (vac-p) individuals (19 vs 7 days and 10(7) vs 10(5) pfu/ml, respectively). In-vitro T-cell proliferative responses to one or more HIV antigen preparations developed in 13 of 16 vaccinia-primed subjects inoculated with HIVAC-1e. T-cell responses were, however, transient and in no subject did antibodies to HIV become detectable. The 2 vaccinia-naive subjects vaccinated with HIVAC-1e showed strong T-cell responses to homologous and heterologous strains of whole virus and to recombinant gp160 protein that remained detectable for over a year; antibodies to HIV envelope also developed in both. Recombinant vaccinia virus vaccines induce T-cell priming to the foreign gene products in most individuals. If used as the sole immunising agent they will be most efficacious in vaccinia-naive individuals.

Adult↗
PubMed1991

Acquired immunodeficiency syndrome. Cerebrospinal fluid findings in patients before and during long-term oral zidovudine therapy.

Fifty-two patients with acquired immunodeficiency syndrome were enrolled in this study to evaluate the relationship between cerebrospinal fluid (CSF) zidovudine concentrations and neurologic and human immunodeficiency virus (HIV) culture findings. Paired HIV-CSF culture and neurologic measurements were available in 30 and 45 patients, respectively. Twenty-nine patients were assessable for zidovudine CSF concentrations. Patients underwent lumbar puncture and neurologic testing before and after 8 weeks or more of oral zidovudine therapy (600 to 1500 mg/d). After 8 weeks of therapy, the frequency of HIV isolation from CSF cultures was unchanged. Significant neurologic improvement by examination was noted in 61.5% (32/52) of the patients. The median CSF zidovudine concentration among 29 patients was 0.047 mg/L (range, 0.015 to 0.198 mg/L). No correlation between CSF zidovudine concentration, cumulative dose, or HIV isolation from CSF and persistence or resolution of neurologic symptoms or signs was observed. The mechanisms by which zidovudine improves neurologic function are unclear and appear unrelated to direct clearance of virus from CSF.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Recovery of human immunodeficiency virus type 1 from semen: minimal impact of stage of infection and current antiviral chemotherapy.

Because exposure to semen is important for the sexual transmission of human immunodeficiency virus type 1 (HIV), the relationship of stage of infection and antiviral chemotherapy to isolation of HIV from semen was investigated. Whereas HIV was isolated from peripheral blood mononuclear cells of all seropositive persons tested, it was isolated from semen in only 11 (32%) of 34 men, including 3 of 6 who were studied sequentially over time. HIV was isolated from 6 (32%) of 19 semen specimens from 14 asymptomatic persons (Centers for Disease Control [CDC] class II or III) and from 10 (28%) of 36 semen specimens from 20 symptomatic patients (CDC class IV). Isolation of HIV from semen did not correlate with CD4+ or CD8+ T lymphocytes counts or zidovudine therapy. Seropositive men may shed HIV in semen early in the course of infection, and zidovudine therapy seems to have no effect on the recovery of HIV and, thus, on the potential for sexual transmission of HIV.

HIV Infections↗
PubMed1991

Fertility parameters in men infected with human immunodeficiency virus.

The effect of human immunodeficiency virus type 1 (HIV) infection on semen parameters that assess fertility was investigated in 50 semen specimens from 21 asymptomatic or minimally symptomatic HIV-seropositive men and 3 specimens from 3 men with AIDS. HIV was isolated from 15 (30%) of 50 specimens from asymptomatic or minimally symptomatic persons and from 1 of 3 specimens from patients with AIDS. The men with AIDS all had pyosemia and grossly abnormal sperm. In contrast, semen specimens from other seropositive men did not differ significantly from semen specimens from healthy seronegative semen donors. No abnormality in sperm count, morphology, numbers or types of leukocytes in semen, or other seminal parameters was associated with HIV shedding in semen. Zidovudine therapy did not affect sperm morphology or seminal characteristics. Thus, although patients with AIDS had abnormal semen, the laboratory parameters that assess fertility were not affected by shedding of HIV in semen or concomitant therapy with zidovudine.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Pharmacokinetic evaluations of low- and high-dose zidovudine plus high-dose acyclovir in patients with symptomatic human immunodeficiency virus infection.

The pharmacokinetics of zidovudine were evaluated in 41 patients with Centers for Disease Control HIV class IVA infection. The patients were assigned escalating doses of zidovudine (300, 600, or 1,500 mg daily) and were randomized to receive either zidovudine alone or zidovudine with a high dose of acyclovir (4,800 mg per day). Single and multiple intravenous- and oral-dose pharmacokinetic studies were performed on days 1 and 7 and weeks 6 and 12 of therapy. Zidovudine concentrations were analyzed by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods. Zidovudine concentrations in serum declined in a biphasic manner, with half-lives ranging from 1 to 2 h, and were independent of acyclovir administration or length of zidovudine therapy. The median time of peak concentrations in serum following oral doses was 0.75 h (range, 0.25 to 3 h). Accumulation of zidovudine in serum was not observed, but the maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve increased proportionally with increased zidovudine doses. Mean day 7 oral Cmax values were 0.20 +/- 0.12, 0.55 +/- 0.33, and 1.0 +/- 0.5 micrograms/ml for 17 patients receiving total daily doses of, respectively, 300, 600, and 1,500 mg of zidovudine alone, whereas Cmax values were, respectively, 0.27 +/- 0.18, 0.43 +/- 0.33, and 1.2 +/- 0.80 micrograms/ml for 15 comparably treated recipients of zidovudine plus acyclovir (P was not significant). The median bioavailability of oral zidovudine was 67% (42 to 120%) and did not vary with dosage. Absolute and apparent total body clearances were similar among the patients given the various zidovudine doses regardless of whether there was concomitant acyclovir therapy. Drug-related toxicities were observed more frequently in the subjects who received high doses of zidovudine than they were in those who received median and low doses of zidovudine (P=0.03). Overall, acyclovir did not influence the disposition of zidovudine over a wide range of zidovudine doses. No unusual toxicities could be attributed to the zidovudine and high-dose acyclovir combination during the 12-week observation period.

Acyclovir↗
PubMed1990

A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.

BACKGROUND: The initially tested dose of zidovudine for the treatment of patients with advanced disease caused by the human immunodeficiency virus type 1 (HIV) was 1500 mg. Although this dose is effective, it is associated with substantial toxicity. METHODS: To evaluate the efficacy and safety of a reduced dose, we conducted a randomized controlled trial in 524 subjects who had had a first episode of Pneumocystis carinii pneumonia. The subjects were assigned to receive zidovudine in either a dose of 250 mg taken orally every four hours (the standard-treatment group, n = 262) or a dose of 200 mg taken orally every four hours for four weeks and thereafter 100 mg taken every four hours (the low-dose group, n = 262). RESULTS: The median length of follow-up was 25.6 months. At 18 months the estimated survival rates were 52 percent for the standard-treatment group and 63 percent for the low-dose group (P = 0.012 by the log-rank test). At 24 months the estimated survival rates were 27 percent for the standard-treatment group and 34 percent for the low-dose group (P = 0.033). In both groups, 82 percent of the subjects had another opportunistic infection, and the length of time to that infection was similar in the two groups (P = 0.56 by the log-rank test). CD4 T-lymphocyte counts improved transiently in both groups, and serum levels of HIV antigen decreased in the subjects with antigenemia. The hemoglobin level declined to less than 5 mmol per liter (80 g per liter) in 101 subjects in the standard-treatment group and in 77 in the low-dose group (39 vs. 29 percent, P = 0.0009 by the log-rank test). The neutrophil count declined to less than 0.750 x 10(9) per liter in 134 subjects in the standard-treatment group and in 96 in the low-dose group (51 vs. 37 percent, P = 0.0001). CONCLUSIONS: The reduced daily dose of zidovudine used in this study was at least as effective as the standard dose and was less toxic; however, with the use of a four-week induction period with a high dose followed by low-dose treatment, severe anemia and neutropenia were common complications of treatment with zidovudine.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A pilot study of low-dose zidovudine in human immunodeficiency virus infection.

BACKGROUND: Zidovudine delays the progression of human immunodeficiency virus (HIV) infection but is associated with hematologic toxicity at high doses. Regimens are needed that preserve or enhance efficacy and reduce toxicity. Acyclovir has been reported to potentiate the effect of zidovudine on HIV in vitro. METHODS: We conducted a Phase II open-label, dose-escalating trial to evaluate the clinical and antiviral effects of zidovudine at low (300 mg daily, 28 subjects), medium (600 mg, 24 subjects), and high (1500 mg, 15 subjects) doses, either with or without acyclovir (4.8 g) by random assignment. The subjects had the acquired immunodeficiency syndrome (AIDS)-related complex, but not AIDS. All of them had either HIV p24 antigenemia or plasma viremia and CD4-lymphocyte counts of 200 to 500 per cubic millimeter when they began treatment. RESULTS: Performance scores and fatigue improved the most in the low- and medium-dose zidovudine groups (both P less than or equal to 0.025). Those assigned to low-dose zidovudine gained the most weight and had the greatest improvement in the mean CD4-lymphocyte count (from 321 per cubic millimeter at base line to 412 per cubic millimeter after 12 weeks, P = 0.01). The proportion of subjects in whom HIV antigenemia resolved, the decrease in the level of antigenemia, and the reduction in the plasma virus titers were similar at all three doses. Subjects assigned to receive the low or medium dose who subsequently crossed over to the 1500-mg dose (n = 19) did not have an increase in CD4-cell counts or a decline in levels of HIV antigen, but they did have dose-related toxicity. The addition of acyclovir to zidovudine was well tolerated, but it did not enhance any of zidovudine's antiretroviral effects. CONCLUSIONS: In this pilot study a very low dose of zidovudine (300 mg) had clinical and virologic effects similar to those of higher daily doses (600 and 1500 mg). The minimal effective dose of zidovudine for the treatment of HIV infection has yet to be determined, and further studies of very low daily doses are warranted.

AIDS-Related Complex↗
PubMed1990

The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group.

OBJECTIVE: To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection. DESIGN: A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts. SETTING: Multicenter trial at AIDS Clinical Trial units. SUBJECTS: Seven hundred eleven subjects with mildly symptomatic HIV infection. INTERVENTION: Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months. MEASUREMENTS AND MAIN RESULTS: Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively. CONCLUSION: Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.

AIDS-Related Complex↗
PubMed1990

The role of age-dependent behaviors in the retention of an approach-avoidance response in preweanling rats.

The role of age-dependent responses in infantile amnesia was examined. Ten- and 15-day old rats were trained in an approach-mother, avoid-shock paradigm and tested for retention immediately and after a 1-day delay. Ten-day-old rats were also tested after 6 days. Half of all the pups received a shock reactivation treatment before the delayed retention tests and half did not. In comparison to immediate retention, performance declined after 1 day but was reinstated by reactivation. A similar reactivation effect was found on 10-day-old pups tested after 6 days except that a different age-specific response was substituted for the original behavior. These effects were not found in untrained controls. These data show that learning may be expressed differently when acquisition and retention are measured at different developmental stages, a pattern that may be mistaken for infantile amnesia.

Aging↗
PubMed1990

Cytomegalovirus infection in women attending a sexually transmitted disease clinic.

To evaluate prospectively the relationship between current and past sexual practices and seroprevalence of cytomegalovirus (CMV) in adult women, 1481 women (1101 white, 301 black, 79 other) attending a sexually transmitted disease clinic underwent a standardized interview and genital examination. CMV seroprevalence was higher in black (78%) than in white (59%) women. In logistic regression models that adjusted for age and years of education, CMV seropositivity in white women was associated with younger sexual debut (P = .001), more lifetime sex partners (P = .025), recent new partner(s) (P = .003), and parity (P = .002), and was inversely associated with use of barrier contraception (P = .006). In black women, after adjustment for demographic characteristics, CMV antibody was associated with greater numbers of recent sex partners (P = .007), new sex partners (P = .04), and with cervical infection with Chlamydia trachomatis (P = .05). This study confirms that sexual activity is an important determinant of CMV infection in both white and black women; however, the relative contributions of sexual and nonsexual transmission of CMV apparently vary and require further investigation.

Adolescent↗
PubMed1990

Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal.

Zidovudine is the only drug currently approved for the treatment of HIV infection. The present recommended doses found to be efficacious in patients with AIDS (200 mg every 4 h) achieve serum zidovudine concentrations greater than 0.267 micrograms/ml (1 mumol/l). Since patients often take zidovudine with food, we have investigated the effect of a liquid high-fat meal on the rate of absorption of zidovudine and on the peak serum concentration achieved. Eight patients received their usual dose of zidovudine (100 mg or 250 mg), with and without a liquid high-fat meal, on two separate study days, in a randomized crossover fashion. Blood and urine samples were collected over a 4-h period. In the absence of food, zidovudine is rapidly absorbed; the time to reach maximal serum concentration (Tmax) was 0.68 (+/- 0.25) h and the mean peak serum concentration (Cmax) achieved was 0.49 (+/- 0.3) micrograms/ml (dose normalized to 100 mg dose). In the presence of a high-fat meal, Tmax was significantly prolonged [1.95 (+/- 0.69) h; P less than 0.05] and the Cmax reduced [0.245 (+/- 0.12) micrograms/ml; P less than 0.05]. This demonstrates that to achieve maximal zidovudine serum concentrations, patients should take this medication on an empty stomach.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Zidovudine disposition during hemodialysis in a patient with acquired immunodeficiency syndrome.

Zidovudine (azidothymidine, AZT) disposition was examined during a hemodialysis session in an HIV-infected male with mesangial proliferative glomerulonephritis. Serum concentrations of zidovudine and its glucuronidated inactive metabolite (G-ZDV) were measured by HPLC. Zidovudine pharmacokinetics were similar to previous reports in patients with normal renal function, however, G-ZDV concentrations were significantly elevated (23-440 times zidovudine concentration). Hemodialysis did not appreciably reduce zidovudine or G-ZDV levels. Significance of chronically elevated G-ZDV levels is unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Plasma viremia in human immunodeficiency virus infection.

To determine which markers of human immunodeficiency virus type 1 (HIV) replication correlate most closely with progressive disease, we compared the following: (1) the frequency of isolation of HIV from peripheral-blood mononuclear cells (PBMC), (2) the frequency of isolation of the virus from cell-free plasma (plasma viremia), (3) the presence and titer of p24 antigen in plasma, and (4) the presence and titer of antibody to p24 antigen. We studied 213 persons who were positive for HIV antibody and 71 who were negative. HIV was isolated from PBMC from 207 of the 213 antibody-positive patients (97 percent), regardless of the clinical stage of the infection. Plasma viremia, in contrast, was correlated with the clinical stage of the infection. It was detected in 11 of 48 patients (23 percent) with asymptomatic infection, 32 of 71 (45 percent) in Class IVa of the Centers for Disease Control (those with AIDS-related complex), and 75 of 92 (82 percent) in Class IVc (those with AIDS) (P less than 0.01). Plasma HIV titers ranged from 10(0) to 10(4.3) and rose from a mean of 10(1.4) in asymptomatic patients to 10(2.5) in those with AIDS (P less than 0.02). Only 45 percent of patients with plasma viremia had HIV p24 antigen in either serum or plasma, and no correlation was found between the amount of p24 antigen in plasma and the plasma HIV titers. Follow-up tests indicated that plasma viremia was associated with a more marked decline in the CD4-lymphocyte cell count and the development of symptomatic disease (P = 0.034). We conclude that plasma viremia is a more sensitive virologic marker of the clinical stage of HIV infection and viral replication than the presence of p24 antigen or antibody in plasma. Not only whole blood but cell-free plasma from HIV-infected patients should be considered potentially infectious.

AIDS-Related Complex↗