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A C Collier

Publications and source records attributed to A C Collier.

At least 73 records · Page 4Linked to original sources
PubMed1995

The predictive value of changes in serologic and cell markers of HIV activity for subsequent clinical outcome in patients with asymptomatic HIV disease treated with zidovudine.

OBJECTIVE: To determine if serologic marker responses to zidovudine treatment during the first year of antiretroviral therapy could predict subsequent HIV disease progression independently of absolute CD4 lymphocyte responses. METHODS: We conducted a case-control study in patients with asymptomatic HIV disease, who were initiating zidovudine therapy in a randomized, prospective trial. A total of 102 patients who progressed to AIDS or advanced AIDS-related complex and 177 randomly selected controls matched by baseline CD4 cell count and duration of follow-up had serum samples (from prior to and at 8, 16, 32 and 48 weeks of zidovudine treatment) assayed for acid-disassociated HIV p24 antigen, beta 2-microglobulin (beta 2M), neopterin, soluble interleukin (IL)-2 receptor, soluble CD4 protein and soluble CD8 protein. RESULTS: Median time to event for cases was 20.2 months; median follow-up on study was 35.4 months for controls. After controlling for absolute CD4 count at baseline, increased baseline serum concentrations of HIV p24 antigen, beta 2M, neopterin, and soluble IL-2 receptor were highly predictive of increased risk of HIV disease progression. In a multiple logistic regression model, controlling for baseline marker values, change in beta 2M consistently added independent value to change in CD4 count in predicting subsequent risk of disease progression. CONCLUSIONS: Monitoring serum immunologic markers, in particular beta 2M, in addition to absolute CD4 lymphocyte counts prior to and within the first 4 months after initiating dideoxynucleoside therapy can increase the accuracy of estimations of subsequent long-term risk of clinical HIV disease progression. This information may be useful to clinicians and patients who are making decisions about initiating or changing antiretroviral therapy.

AIDS-Related Complex↗
PubMed1995

Clinical pharmacokinetics of adefovir in human immunodeficiency virus type 1-infected patients.

The pharmacokinetics and bioavailability of adefovir [9-[2-(phosphonomethoxy)ethyl]adenine] were examined at two dose levels in three phase I/II studies in 28 human immunodeficiency type 1-infected patients. The concentrations of adefovir in serum following the intravenous infusion of 1.0 or 3.0 mg/kg of body weight were dose proportional and declined biexponentially, with an overall mean +/- standard deviation terminal half-life of 1.6 +/- 0.5 h (n = 28). Approximately 90% of the intravenous dose was recovered unchanged in the urine in 12 h, and more than 98% was recovered by 24 h postdosing. The overall mean +/- standard deviation total serum clearance of the drug (223 +/- 53 ml/h/kg; n = 25) approximated the renal clearance (205 +/- 78 ml/h/kg; n = 20), which was significantly higher (P < 0.01) than the baseline creatinine clearance in the same patients (88 +/- 18 ml/h/kg; n = 25). Since adefovir is essentially completely unbound in plasma or serum, these data indicate that active tubular secretion accounted for approximately 60% of the clearance of adefovir. The steady-state volume of distribution of adefovir (418 +/- 76 ml/kg; n = 28) suggests that the drug was distributed in total body water. Repeated daily dosing with adefovir at 1.0 mg/kg/day (n = 8) and 3.0 mg/kg/day (n = 4) for 22 days did not significantly alter the pharmacokinetics of the drug; there was no evidence of accumulation. The oral bioavailability of adefovir at a 3.0-mg/kg dose was < 12% (n = 5) on the basis of the concentrations in serum or 16.4% +/- 16.0% on the basis of urinary recovery. The subcutaneous bioavailability of adefovir at a 3.0-mg/kg dose was 102% +/- 8.3% (n = 5) on the basis of concentrations in serum or 84.8% +/- 28.5% on the basis of urinary recovery. These data are consistent with preclinical observations in various species.

Adenine↗
PubMed1995

Intermittent shedding of human immunodeficiency virus in semen: implications for sexual transmission.

PURPOSE: We attempt to increase our understanding of human immunodeficiency virus (HIV) shedding in semen. MATERIALS AND METHODS: We followed 16 seropositive men for up to 27 months by HIV cocultivation, with a subset evaluated using the polymerase chain reaction. RESULTS: The proportion with at least 1 HIV positive semen culture increased from 3 of 16 subjects (19%) at visit 1 to 10 (63%) by visit 5. Overall, HIV was cultured from 25 of 114 specimens (22%). Shedding was intermittent for each of the 10 men with at least 1 positive culture and seminal shedding patterns were highly variable. CONCLUSIONS: By culture and polymerase chain reaction, HIV is shed intermittently in the semen. If cultures are performed often enough most seropositive men shed HIV in the semen.

Base Sequence↗
PubMed1994

Stress-induced modulation of the immune response in the developing rat pup.

Although substantial evidence has linked stressful events to immune changes in adult animals, little is known regarding the impact of stress on immune function during ontogeny. In the present study, 8-, 16-, and 20-day old rat pups were isolated from their mothers and littermates for 24 h; splenocyte responses to the mitogen Con A were assessed 72 h following reunion. A suppression of the mitogen response was obtained for 16- and 20-day old pups, but no effect was found in the 8-day-old animals, possibly due to the small sample size. These data offer a viable model from which to study further changes in immune responsiveness during ontogeny.

Aging↗
PubMed1994

Early intervention in HIV infection: where are we?

Data about the virology and pathogenesis of HIV disease suggest that early therapeutic intervention, perhaps even before the CD4+ cell count has fallen substantially, would be a theoretically sound approach. A limited number of large clinical studies address early therapy with zidovudine. A European-Australian study, which enrolled patients with CD4+ cell counts > 400 cells/microliters, found a benefit of zidovudine therapy compared to placebo in delaying minor HIV manifestations and CD4+ cell loss after a 2-year follow-up period. The results of the Concorde study, which enrolled > 1700 asymptomatic patients and followed them for an average of 3 years, have created controversy about the results of ACTG protocol 019, which had led to widespread zidovudine use for patients with CD4+ cells < 500/microliters. Although there was a favorable change in CD4+ cell count in the Concorde study patients assigned to immediate zidovudine treatment compared with those assigned to deferred treatment, there were no significant differences in progression to AIDS or survival. Preliminary results from follow-up of ACTG 019 patients enrolled with CD4+ cell counts of 300-500/microliters suggest that the duration of benefit of zidovudine may be longer than in patients with CD4+ cell counts less than 300 cells/microliters. Finally, the impact of antiretroviral therapy on quality-of-life measures is now recognized as an important issue and should be incorporated into treatment decisions. The available data from several large studies of patients with asymptomatic HIV infection are concordant, in that they suggest that zidovudine has a limited duration of efficacy but does not prolong survival.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4 Lymphocyte Count↗
PubMed1994

The effects of high-dose recombinant soluble CD4 on human immunodeficiency virus type 1 viremia.

In vitro, low-passage clinical human immunodeficiency virus type 1 (HIV-1) isolates require up to 1000 times greater serum levels of recombinant soluble CD4 (rsCD4) than have ever been given. To determine if sufficient serum levels of rsCD4 provide in vivo inhibition of HIV-1, 4 HIV-1 plasma-viremic subjects were given single-dose boluses of 2, 4, 6, 8, and 10 mg/kg intravenous rsCD4. Plasma HIV-1 cultures were done after infusion. Three subjects demonstrated a dose-dependent reduction in plasma HIV-1 viremia. The inhibitory effect of rsCD4 on plasma HIV-1 viremia was associated with the in vitro ID90-95 of the isolate, not the ID50. These data demonstrate that extremely high doses of rsCD4 inactivate cell-free HIV-1 in vivo and suggest that high doses of rsCD4 may have some short-term therapeutic utility, such as with accidental or occupational HIV-1 exposure.

CD4 Antigens↗
PubMed1994

Human herpesvirus 6 DNA in blood cells of human immunodeficiency virus-infected men: correlation of high levels with high CD4 cell counts.

The relationship between human herpesvirus 6 (HHV-6) and the progression of human immunodeficiency virus type 1 (HIV-1) infection to AIDS was evaluated using the polymerase chain reaction to quantitate HHV-6 genome equivalents in peripheral blood mononuclear cells (PBMC) and saliva of 32 HIV-1-seropositive men. Unlike other herpesviruses, HHV-6 was found with higher frequency and in higher copy numbers of HIV-infected men with high rather than low CD4 cell counts. Among subjects with > 400 CD4 cells/mL, 100% had detectable HHV-6 genomes in PBMC compared with 57.9% of subjects with < 400 CD4 cells/mL (P < .05). There was no significant correlation between HHV-6 antibody titer or number of amplifiable copies of HHV-6 DNA in saliva and stage of HIV disease or CD4 cell number.

AIDS-Related Opportunistic Infections↗
PubMed1994

Foscarnet for suppression of human immunodeficiency virus replication.

The effect of foscarnet against human immunodeficiency virus (HIV) was evaluated in nine HIV-infected individuals; six completed 28 days of induction therapy. The overall mean increase in CD4+ lymphocytes was 64 cells per mm3. The mean decline in the HIV antigen concentration was 108 pg/ml (P = 0.03), and suppression was related to systemic foscarnet exposure by a maximum-effect pharmacodynamic model.

Adult↗
PubMed1994

Changing use of intensive care for HIV-infected patients with Pneumocystis carinii pneumonia.

Clinicians' approach to acute respiratory failure from Pneumocystis carinii pneumonia (PCP) is hypothesized to have gone through three phases: aggressive management due to an absence of data on prognosis (1981-84), withholding of intensive care based on a few small studies showing high case fatality (1985-87), and an increase in intensive care to an intermediate level (1988 forward). Unfortunately, studies of survival from acute respiratory failure among such patients have been small and have been limited to patients in the intensive care unit. To determine whether this three-phase scenario has empirical support, we performed a retrospective chart review of all patients with human immunodeficiency virus (HIV) infection and PCP at a university-affiliated municipal hospital from 1983 to 1990. We identified 180 patients, representing 218 episodes of PCP. The previously hypothesized relationship between intensive care and year of diagnosis was confirmed: intubation rates were 30% before 1985, 0% in 1987, and 12% after 1988 (p = 0.03). Among all patients, the percentage dying in the hospital without intensive care had the opposite relationship with year of diagnosis, increasing from 0% in 1984 to 21% in 1987 and then declining to 0% in 1990 (p = 0.001). Overall mortality from an episode of PCP was 25% and did not change significantly over time. Disease severity also did not change significantly over time. In summary, the significant swings in the use of intensive care for HIV-infected patients with PCP suggest that judgments about the futility of intensive care were strongly influenced by incorrect perceptions of survival.

AIDS-Related Opportunistic Infections↗
PubMed1994

The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3.

We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC-48334) (an alpha-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated < or = 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 +/- 0.99 micrograms/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Deoxynojirimycin↗
PubMed1993

Combination therapy with zidovudine and didanosine compared with zidovudine alone in HIV-1 infection.

OBJECTIVE: To assess safety, pharmacokinetics, and in-vivo virologic activity of five different combination regimens of zidovudine and didanosine compared with zidovudine alone in patients with human immunodeficiency virus type 1 (HIV-1) infection. DESIGN: Open-label, partially randomized, dose-ranging study. SETTING: University-affiliated, medical center clinics. PATIENTS: A total of 69 patients with HIV-1 infection, CD4+ cell counts fewer than 400 cells/mm3, and fewer than 121 days of previous zidovudine treatment. INTERVENTIONS: Fifty-five patients received combination therapy with zidovudine and didanosine, and 14 received zidovudine therapy alone (600 mg/d). Daily dosages in milligrams of zidovudine and didanosine, respectively, in the five combination groups were 150 and 90 mg, 300 and 334 mg, 600 and 334 mg, 300 and 500 mg, and 600 and 500 mg. MEASUREMENTS: CD4+ cell counts, HIV-1 RNA titers in plasma, and toxic effects. RESULTS: The combination regimens were associated with higher and more sustained increases in CD4+ cells than zidovudine alone, even after adjustment for initial CD4+ counts and previous zidovudine therapy (P < 0.001). The median increase in CD4+ cell counts was 166 cells/mm3 with combination therapy and 77 cells/mm3 with zidovudine alone (P = 0.001) and did not differ statistically among the five combination regimens. Human immunodeficiency virus type 1 RNA titers in plasma decreased in 15 (83%) of 18 combination-therapy recipients compared with 2 of 7 zidovudine-alone recipients (P = 0.017). No pharmacokinetic interactions were seen between zidovudine and didanosine. Toxicity rates were low among all treatment groups. A greater decrease in hemoglobin levels was seen with the regimen using zidovudine alone (-8 g/L) compared with combination regimens using the same zidovudine dose (-1.5 g/L, P = 0.03). CONCLUSIONS: Combination therapy with zidovudine and didanosine produced larger and more sustained increases in CD4+ cell counts, more frequent decreases in plasma HIV-1 RNA titers, and more stable hematologic status than zidovudine therapy alone. The effects of this combination on the progression of HIV disease merit further study, to provide information about clinical outcome, because this was a relatively small study based on surrogate markers of HIV-1 infection.

Adult↗
PubMed1993

Enhanced immunity to human immunodeficiency virus (HIV) envelope elicited by a combined vaccine regimen consisting of priming with a vaccinia recombinant expressing HIV envelope and boosting with gp160 protein.

Transmission studies have suggested that an optimal human immunodeficiency virus type 1 (HIV-1) vaccine should induce both neutralizing antibodies and cytolytic T cells to eliminate free virus and infected cells. A phase I trial in healthy HIV-1-seronegative persons was conducted with a combination HIV-1 vaccine regimen (strain IIIB) consisting of priming with a recombinant vaccinia (vac/env) virus expressing HIV-1 envelope and boosting with a gp160 glycoprotein derived from a recombinant baculovirus (rgp160). T-cell and antibody responses detected after immunization with either vac/env alone or rgp160 alone were generally of low magnitude and transient, and no subject developed neutralizing antibodies. In contrast, recipients of the combination regimen demonstrated in vitro T-cell proliferative responses to homologous HIV-1 antigens that were 3- to 10-fold higher than responses with either vaccine alone, and these responses were sustained for > 18 months in 75% of recipients. Moreover, both CD8+ and CD4+ cytolytic T cells were detected. Antibody responses (titer, 1:800 to 1:102,400) to homologous HIV envelope developed in all recipients of the combination regimen, and neutralizing antibodies were detected in 7 of 13. Thus, immunization with a live virus vaccine followed by boosting with a soluble protein offers promise for inducing the broad immunity needed in an HIV vaccine.

Baculoviridae↗
PubMed1993

Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. AIDS Clinical Trials Group.

The efficacy of two doses of zidovudine was examined for the treatment of the acquired immunodeficiency syndrome (AIDS) dementia complex in a randomized, double-blinded, placebo-controlled trial conducted at nine study centers. For the initial 16 weeks, 40 subjects with mild to moderate AIDS dementia complex were randomized to one of three treatment arms: 400 mg of zidovudine five times daily, 200 mg of zidovudine five times daily, or placebo five times daily. After week 16, patients initially randomized to the placebo group were rerandomized to one of the two zidovudine treatment arms. The primary efficacy end point was improvement in performance on a battery of seven neuropsychological tests; the secondary end point was improvement on a protocol neurological evaluation directed at the cardinal features of the AIDS dementia complex. For the initial 16-week period, average z scores based on the neuropsychological test battery revealed a significant improvement in the combined treatment groups compared to the placebo group; however, when the two treatment groups were compared separately to the placebo group, only the group receiving the higher zidovudine dose exhibited significant improvement. After rerandomization of the placebo patients to one of the two treatment arms at week 16, this group also showed significant improvement in the average neuropsychological z score by week 32. These results extend previous observations that indicate a therapeutic benefit of zidovudine for the treatment of AIDS dementia complex.

AIDS Dementia Complex↗
PubMed1993

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AIDS-Related Opportunistic Infections↗
PubMed1993

Cognitive risk factors and neuropsychological performance in HIV infection.

Almost all investigations examining the effects of early HIV infection on neuropsychological functioning in homosexual males have excluded subjects with cognitive risk factors such as recreational drug use and head injury. While insuring that results reflect the influence of the virus on cognition, this selection bias limits the ability to generalize findings. Comprehensive neuropsychological evaluations were compared between two groups of homosexual males with a variety of cognitive risk factors. Subjects were 132 HIV seropositive males (108 CDC class II & III and 24 CDC class IVA & IVC2) and 65 HIV seronegative controls. Recreational drug use in the six months prior to exam was found to interact with HIV infection and was associated with selective areas of cognitive decline and a significantly worse overall neuropsychological performance. Although significantly lower functioning in the domains of Verbal Memory and Attention and Speed of Information processing was noted for subjects with CDC class IVA and IVC2 compared to seropositives with CDC class II & III, overall neuropsychological performance was similar in these two groups. At this early stage of HIV infection, we did not find indication of association between neuropsychological performance and decreased immunological status. A history of head injury and recent recreational drug use emerged as primary cognitive risk factors associated with decreased neuropsychological performance. As 50% of our HIV seropositive subjects reported active recreational drug use, this cognitive risk factor in particular may contribute to the appearance of HIV-related cognitive deficits during early stages of HIV infection.

Cognition Disorders↗
PubMed1992

A randomized, double-blind, phase I/II trial of tumor necrosis factor and interferon-gamma for treatment of AIDS-related complex (Protocol 025 from the AIDS Clinical Trials Group).

To determine safety and efficacy of tumor necrosis factor (TNF) and interferon-gamma (IFN gamma) in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related complex, a randomized, double-blind study was conducted. Twenty-five patients with AIDS-related complex and CD4 lymphocytes less than or equal to 500 x 10(6)/L attended an AIDS Clinical Trials Unit of a tertiary referral center. Patients were administered tumor necrosis factor (TNF) (10 micrograms/m2) or IFN gamma (10 micrograms/m2), or both intramuscularly three times weekly for 16 weeks. Side effects from all three preparations included fever, constitutional symptoms, and local reactions. No significant hematologic, hepatic, renal, or coagulation abnormalities were observed. CD4 lymphocyte counts, beta 2-microglobulin, p24 antigen levels, and anti-p24 antibody did not change significantly during therapy. Similarly, no significant change was noted in rates of HIV isolation from peripheral blood mononuclear cells or plasma. TNF and IFN gamma were tolerable after premedication with acetaminophen; however, no significant change in markers of human immunodeficiency virus infection was demonstrated. These cytokines alone do not appear to be of benefit, nor do they appear to hasten the progression of HIV infection.

AIDS-Related Complex↗