Biomedical subjects

C W Hendrix

Publications and source records attributed to C W Hendrix.

48 records · Page 3Linked to original sources

PubMed1992

Comparison of antibody reactivity to human immunodeficiency virus type 1 (HIV-1) gp160 epitopes in sera from HIV-1-infected individuals from Tanzania and from the United States.

In this study, we compared sera from 159 human immunodeficiency virus type 1 (HIV-1)-infected individuals from Tanzania and 103 infected individuals from the United States for antibodies reactive with 10 HIV-1 gp160 epitopes defined by synthetic peptides. Our data indicate that the anti-gp160 antibody fine specificity differs between infected individuals from these two geographically diverse populations. For example, 50% of the Tanzanian sera contained antibodies reactive with an immunodominant HIV-1 gp41 epitope defined by peptide 600-611, whereas 91% of the sera from the United States were reactive. Differences in serologic reactivity between HIV-1-infected individuals from Tanzania and the United States were also observed with gp160 epitopes defined by peptides 503-528 and 846-860. Included among the peptides examined were four which corresponded to the V3 region of gp120. The majority of sera from either country contained antibodies reactive with peptide RP142, whose V3 sequence is based upon that of HIV-1 isolate MN. Further characterization of serologic reactivity suggested that sera from Tanzania were more likely to neutralize HIV-1 isolate IIIB or MN in vitro than were sera from the United States. These differences in antibody fine specificity between HIV-1-infected individuals from Tanzania and the United States suggest that regional isolates of HIV-1 may exist.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Examination of sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals for antibodies reactive with peptides corresponding to the principal neutralizing determinant of HIV-1 gp120 and for in vitro neutralizing activity.

Sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals from the United States and Tanzania were examined for antibody reactivity to four synthetic peptides which corresponded to the principal neutralizing determinant from the V3 region of HIV-1 gp120. We observed that the majority of sera from both countries contained antibodies reactive with a V3 peptide whose sequence is based on that of the HIV-1 MN isolate. We were unable to establish a relationship between the presence of V3-reactive antibodies, as measured by enzyme-linked immunosorbent assay and neutralization of homologous HIV-1 isolates, in sera from either the United States or Tanzania. We observed that some sera which contained high antibody titers to the V3 peptides failed to neutralize HIV-1, while others with no antibody reactivity to the panel of V3 peptides exhibited in vitro neutralizing activity. These results suggest that neutralizing epitopes exist outside the V3 loop and that the presence of V3-reactive antibodies in sera does not imply in vitro neutralization of the homologous HIV-1 isolate. In addition, it appears that the V3 loop may consist of both neutralizing and nonneutralizing epitopes. The identification of neutralizing as well as nonneutralizing epitopes will be important for the design of potential HIV-1 vaccines.

Amino Acid Sequence↗

PubMed1992

Comparison by race of total serum IgG, IgA, and IgM with CD4+ T-cell counts in North American persons infected with the human immunodeficiency virus type 1.

European patients with human immunodeficiency virus type 1 (HIV-1) infection have been reported to have lower titers of anti-p24 antibody than Central African HIV seropositive patients. Recently, black HIV positive patients in the United States were reported to be more likely to have detectable anti-p24 antibodies, less p24 antigenemia, and higher combined serum immunoglobulins than white HIV positive patients. We measured individual total serum immunoglobulins in 853 HIV positive patients (94% male; 58% white and 42% black) on their initial medical evaluation and compared them with CD4+ T-cell counts. Blacks had notably higher IgG levels (p = 0.001) across the entire spectrum of CD4+ T-cell counts. Serum IgM levels were slightly higher in blacks. IgA levels were not significantly different between the races, although the trend (p = 0.006) was toward higher levels in whites. We also measured these three serum immunoglobulins in 60 HIV seronegative, healthy blood donors (30 black and 30 white). In this control group, blacks had statistically higher IgG and IgA levels than whites. A review of the literature prior to the HIV/acquired immune deficiency syndrome epidemic also supports the view that racial differences in IgG levels are not specific for HIV infection. We speculate that racial differences in humoral immunity, independent of geography or strain of HIV, may account for differences in anti-HIV antibody levels and HIV antigenemia.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Comparison of spinal fluid beta 2-microglobulin levels with CD4+ T cell count, in vitro T helper cell function, and spinal fluid IgG parameters in 163 neurologically normal adults infected with the human immunodeficiency virus type 1.

Beta 2-microglobulin levels were measured in the cerebrospinal fluid (CSF) and serum of 163 human immunodeficiency virus-positive (HIV+) persons with normal neurologic physical examinations. None were on antiretroviral therapy. Only 3% had a positive CSF HIV p24 antigen test. The CSF beta 2-microglobulin levels increased as the CD4+ T cell count decreased. Intrathecal production of beta 2-microglobulin was suggested by finding CSF concentrations greater than serum concentrations in 15% of patients. The CSF beta 2-microglobulin levels rose as in vitro T helper cell function deteriorated, independent of CD4+ T cell count. CSF beta 2-microglobulin levels paralleled CSF IgG, IgG index, and IgG synthesis. Higher CSF beta 2-microglobulin levels were found in persons with positive CSF oligoclonal bands. CSF beta 2-microglobulin concentration may serve as a marker for subclinical neurologic damage due to HIV. If this is established, defining the effect of anti-HIV interventions on CSF beta 2-microglobulin would be warranted.

Albumins↗

PubMed1991

Human immunodeficiency virus infection in the US Air Force: seroconversions, clinical staging, and assessment of a T helper cell functional assay to predict change in CD4+ T cell counts.

As of January 1990, 933 persons with human immunodeficiency virus type 1 (HIV-1) infection were clinically evaluated at Wilford Hall US Air Force (USAF) Medical Center. The Walter Reed HIV staging system was used in these evaluations to describe disease status and progression. Most persons were diagnosed through mandatory HIV testing in the USAF and were asymptomatic at the time of diagnosis. As of May 1990, 161 HIV-positive seroconverters (estimated overall seroconversion rate of 0.156/1000 person-years between 30 June 1988 and 1 July 1990) had been identified among active-duty USAF personnel, as they had previously tested negative for antibody to HIV. Men constitute 95% of the USAF HIV-positive population. An in vitro T helper cell functional assay was assessed to predict rate of CD4+ T cell decline over the subsequent year (mean, 15 months) in patients with greater than 200 CD4+ T cells/mm3. This assay may prove useful for prognostication and comparisons of patients in clinical trials of anti-HIV interventions.

Adult↗

PubMed1991

Human immunodeficiency virus reverse transcriptase T helper epitopes identified in mice and humans: correlation with a cytotoxic T cell epitope.

T cell immunity may be critical to development of a vaccine for human immunodeficiency virus (HIV-1). T helper epitopes were identified in three predominantly conserved regions in the HIV-1 reverse transcriptase by using reverse transcriptase-immunized mice of five major histocompatibility complex haplotypes. One peptide (residues 38-52) that stimulated H-2k T cells also contained an epitope recognized by cytotoxic T cells from the same mice and from HIV-infected patients. Such concordance between helper and cytotoxic T lymphocyte epitopes, observed in four cases, may be important in vaccine development. Peptide 36-52 was recognized by interleukin-2-producing peripheral blood T cells from 9 of 17 HIV-seropositive humans studied, of multiple human leukocyte antigen-DR and -DQ types. The broad recognition of this peptide by both helper and cytotoxic T cells substantiates its potential importance in a vaccine.

Adult↗

PubMed1991

Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection.

Polysulfated polysaccharides are attractive candidates for antiviral drug development because of their potent in vitro activities against human immunodeficiency virus (HIV), herpesviruses, and other enveloped viruses. To determine the potential anti-HIV activity of a prototypical polysulfated polysaccharide, we administered the maximally tolerated dose of dextran sulfate by continuous intravenous infusion to 10 subjects with symptomatic HIV infection for up to 14 days. Since parenteral dextran sulfate is an anticoagulant, the infusion was adjusted to produce the greatest acceptable increase in activated partial thromboplastin time. Drug concentrations in plasma achieved with this protocol were up to 200-fold greater than the 50% inhibitory concentration for free HIV infectivity in vitro. Despite this, circulating HIV antigen (p24) levels increased in all eight subjects who received the drug for more than 3 days (median proportional increase, 73.5%; range, 32 to 130%); this increase was highly significant when it was compared with that in a large cohort of untreated historical controls (Fisher's exact test, P less than 0.001). Frequent decreases in infusion rate were required in all subjects to maintain a constant activated partial thromboplastin time; plasma dextran sulfate levels did not fall as the infusion rate decreased, suggesting a decline in estimated drug clearance over time. Continuous intravenous dextran sulfate was toxic, producing profound but reversible thrombocytopenia in all eight subjects who received drug for more than 3 days and extensive but reversible alopecia in five of these subjects. Because of its toxicity and lack of beneficial effect on surrogate markers, dextran sulfate is unlikely to have a practical role in the treatment of symptomatic HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1991

HIV antigen variability in ARC/AIDS.

To define the natural variability of human immunodeficiency virus p24 antigen (HIV Ag) over time in untreated HIV-infected patients, we analyzed the percentage change of serum HIV Ag in 40 antigenemic ARC/AIDS subjects receiving placebo in a 24 week clinical trial. When grouped by month of observation, no differences in HIV Ag change were seen among all five 1 month observation periods (p greater than 0.4). After all 105 monthly changes (median of 3 per subject) were pooled, the mean monthly HIV Ag change was 0% change (standard deviation: 77% increase, 44% decrease). Furthermore, HIV Ag changes did not differ among all lengths of observation (from 1 to 5 months using all possible pairwise combinations of HIV Ag levels, p greater than 0.4). CD4 T-cell changes over the whole study did not correlate with HIV Ag changes over the same period. Knowledge of this broad HIV Ag variability should be useful in calculating sample size and in choosing categorical responses unlikely to occur spontaneously in clinical trials of antiviral agents where HIV Ag changes are used as surrogate markers of efficacy.

AIDS-Related Complex↗

PubMed1990

Hepatitis C antibody in a non-hemophiliac cohort infected with the human immunodeficiency virus.

Development of a serologic test which detects antibody to hepatitis C virus (anti-HCV) allowed us to compare the seroprevalence of hepatitis C and hepatitis B in 493 persons infected with the human immunodeficiency virus (HIV). These persons, none of whom are hemophiliacs, are part of the US Air Force HIV Natural History Study. We found that Hepatitis B core antibody (anti-HBc) was far more prevalent (59%) than anti-HCV (8%). Anti-HBc prevalence was not different between those with and those without anti-HCV, being present in the majority of persons in both groups. In addition, we compared anti-HCV+ and anti-HCV negative persons in terms of syphilis serologies (Reactive Plasma Reagent [RPR] and Fluorescent Treponemal Antibody Absorption [FTA-ABS]), hepatic transaminase levels, and racial composition. In this cohort, we found that anti-HCV+ persons are significantly more likely to have a positive RPR but not FTA-ABS, increased hepatic transaminase levels, and to be Black rather than Caucasian.

Adult↗

PubMed1989

Dextran sulfate is poorly absorbed after oral administration.

STUDY OBJECTIVE: To determine whether dextran sulfate (molecular weight, 7000 to 8000 daltons; 17% to 20% sulfur), a synthetic heparin analogue with anti-human immunodeficiency virus (HIV) activity in vitro, is absorbed after oral administration. DESIGN: Open-label, single-center study in two parts. The first part was a bioavailability study in which six subjects received a single 1800-mg oral dose and a single 225- or 300-mg intravenous dose. The second part was a study of the dose-response relation between dextran sulfate and total plasma lipolytic activity in which twelve subjects were given a single infusion of either 0.05, 0.5, 5, or 50 mg of dextran sulfate. SUBJECTS: Eighteen healthy volunteers. MEASUREMENTS AND MAIN RESULTS: In the bioavailability study, plasma and urine dextran-sulfate concentrations were measured by a competitive binding assay after each dose. In addition, two bioassays were used to assess plasma concentrations: plasma lipolytic activity and activated partial thromboplastin time (APTT). After the oral dose, plasma concentrations were not measurable with the competitive binding assay (lower limit of sensitivity, 1 microgram/mL); less than 0.5% of the dose was recovered in the urine, the APTT did not increase, and the median increase in the plasma lipolytic activity was only twofold (maximum increase, 11-fold). In contrast, after the intravenous dose of 225 mg, peak plasma concentrations by competitive binding assay were 26 to 35 micrograms/mL (median, 28 micrograms/mL); 25% to 29% (median, 25%) of the dose was recovered in the urine; the APTT increased to 3.5 to 9.2 times the baseline value (median increase, 6.9 times), and the plasma lipolytic activity increased by 185 to 548 times the baseline value (median increase, 438 times). In the dose-response study, intravenous doses as low as 0.5 mg produced significant increases in the plasma lipolytic activity. There was a steep dose-response curve between 0.5 and 50 mg. CONCLUSION: Dextran sulfate is very poorly absorbed after oral administration.

Administration, Oral↗

PubMed1989

Probenecid and zidovudine metabolism.

The effects of probenecid, a known inhibitor of glucuronidation, on the pharmacokinetics of zidovudine were assessed in eight subjects receiving zidovudine as treatment for human immunodeficiency virus infection. Zidovudine plasma concentrations were measured while subjects were receiving zidovudine alone, after 3 days of zidovudine plus 500 mg probenecid every 8 h, and after 3 days of zidovudine plus 500 mg probenecid plus 260 mg quinine sulphate every 8 h. A median increase of 80% in the area under the zidovudine plasma concentration/time curve occurred with the addition of probenecid. Quinine sulphate prevented the probenecid effect but had no effect on zidovudine kinetics when taken without probenecid by four other subjects. All of the effects were secondary to changes in zidovudine metabolism, since neither probenecid nor quinine changed the renal elimination of zidovudine. Probenecid could be used in combination with zidovudine to extend the interval between doses and reduce the daily requirement for zidovudine, thus enhancing convenience and reducing costs.

AIDS-Related Complex↗

PubMed1989

Ceftriaxone compared with cefotaxime for serious bacterial infections.

Ceftriaxone was compared with cefotaxime for the treatment of serious bacterial infections in a prospective, randomized, double-blind clinical trial. The dose of ceftriaxone was 2 g once a day, and the dose of cefotaxime was 2 g every 4 h. Metronidazole was added if anaerobic infection was suspected. Explicit criteria were used to define infections, clinical response, and adverse effects. Ceftriaxone was given to 88 patients and cefotaxime to 83. The two treatment groups did not differ in types of infection, infecting organisms, and severity of underlying disease. The response rate was 81% (71/88) for ceftriaxone and 80% (66/83) for cefotaxime. The power of the study to detect a 15% difference in response rate at P less than .1 was 90%. The frequency of diarrhea, thrombophlebitis, prothrombin time, prolongation, colonization, and superinfection did not differ between treatment groups. Ceftriaxone 2 g once a day was as safe and effective as cefotaxime 2 g every 4 h for suspected serious bacterial infections.

Adult↗