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Biomedical subjects

T Schacker

Publications and source records attributed to T Schacker.

26 records · Page 2Linked to original sources
PubMed1996

Clinical and epidemiologic features of primary HIV infection.

BACKGROUND: The acute clinical events surrounding the acquisition of human immunodeficiency virus (HIV) have not been well characterized. OBJECTIVE: To further define the clinical and epidemiologic presentation of primary HIV infection. DESIGN: Descriptive cohort study. SETTING: University research clinic. PATIENTS: 46 adults (43 men and 3 women) with primary HIV infection who enrolled in the study a median of 51 days after HIV seroconversion. MEASUREMENTS: Documentation of recent HIV seroconversion. Standardized collection of demographic characteristics and sexual contact history, results of tests for HIV RNA, HIV culture, and T-cell subsets. RESULTS: 41 of 46 patients (89%) developed an acute retroviral syndrome. Primary HIV infection was infrequently diagnosed at the initial medical encounter, even in persons enrolled in routine HIV screening programs. Median numbers of sexual partners 6 months and 1 month before acquisition of HIV were three and one, respectively; 21 patients (46%) reported having had only one partner in the month before seroconversion. Of the 12 patients who could identify the precise date of and activity leading to seroconversion, 4 reported having only oral-genital contact. CONCLUSIONS: Primary HIV infection causes a recognizable clinical syndrome that is often underdiagnosed, even in persons enrolled in a program of routine surveillance for HIV infection. Frequency of sexual contact and overall numbers of sexual partners in this group of homosexual men who acquired HIV were markedly lower than those seen a decade ago. Acquisition of HIV does occur, even in persons with relatively few sexual partners. Increased attention to oral-genital contact as a means of acquiring HIV appears to be warranted.

Adult↗
PubMed1995

Phase I study of high-dose, intravenous rsCD4 in subjects with advanced HIV-1 infection.

In vitro, recombinant soluble CD4 (rsCD4) attaches to and inactivates human immunodeficiency virus (HIV). To determine if prolonged therapy with high-dose intravenous rsCD4 provides an in vivo benefit, we gave three HIV-1-infected patients with AIDS, whose isolates were susceptible in vitro to rsCD4, 10 mg/kg of rsCD4 for 4 weeks, 5 mg/kg for 4 weeks, and 1 mg/kg for 2 weeks. Single-dose pharmacokinetic studies performed prior to this showed transient in vivo decreases of HIV-1 plasma viremia in all three subjects. Surrogate markers of HIV activity, clinical status, HIV-1 p24 antigen, plasma HIV-1 titers, and peripheral blood mononuclear cell (PBMC) intracellular titers of virus were measured at entry, and every other week after onset of therapy. All subjects demonstrated rsCD4 concentration-dependent reduction in plasma viremia, with two subjects having complete neutralization of cell-free virus. The third subject's isolate was relatively resistant to the in vivo effects of rsCD4 and only partial reduction in plasma virus titers was obtained, even at the highest dose of 10 mg/kg. There was no change in the PBMC intracellular viral titer or surrogate markers of HIV-1 activity (including CD4 cell count and beta 2-microglobulin). There was subjective improvement in clinical symptoms, and all subjects gained weight with the highest doses of rsCD4. rsCD4 exhibited linear pharmacokinetics over the dose range studied. We conclude that high-dose intravenous rsCD4 can be safely given for up to 10 weeks and that it has a stable pharmacokinetic profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
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↗
PubMed1993

Potential for combined therapy with 348U87, a ribonucleotide reductase inhibitor, and acyclovir as treatment for acyclovir-resistant herpes simplex virus infection.

Inhibitors of the ribonucleotide reductase of herpes simplex viruses (HSV) potentiate the activity of acyclovir in vitro and in animal studies. In addition, the combination of the ribonucleotide reductase inhibitor 348U87 and acyclovir has synergistic therapeutic effects against infections in mice due to thymidine kinase-deficient, thymidine kinase-altered, and DNA polymerase mutants of HSV. We performed a pilot study of topical combination therapy with 348U87 (3%) and acyclovir (5%) cream for acyclovir-resistant, anogenital HSV infections in ten human immunodeficiency virus (HIV)-infected patients. Our results, with lack of complete reepitheliazation of lesions in all patients and poor virologic response, suggest that this therapy is unlikely to be useful for this indication.

Acyclovir↗
PubMed1993

Topical treatment of infection with acyclovir-resistant mucocutaneous herpes simplex virus with the ribonucleotide reductase inhibitor 348U87 in combination with acyclovir.

The thiocarbonohydrazone 348U87 inactivates herpes simplex virus ribonucleotide reductase and potentiates the activity of acyclovir against wild-type and acyclovir-resistant strains of herpes simplex virus. We treated 10 human immunodeficiency virus-infected patients with acyclovir-resistant anogenital herpes simplex virus infection with a topical preparation of 348U87 (3%) in combination with acyclovir (5%) in an open-labelled study. Transient improvement with combination therapy occurred frequently; however, target lesions reepithelialized completely in only 1 of 10 patients. Termination of study drug therapy was most often due to cessation of therapeutic effect before complete resolution of lesions. As currently formulated, topical 348U87 offers little therapeutic benefit for this indication.

Acyclovir↗