Patrones radiológicos de la tuberculosis pulmonar en pacientes con infección VIH: correlación con el índice de linfocitos CD4 en sangre / Radiological features of pulmonary tuberculosis in human immunodeficiency virus-infected patients: correlation with the blood CD4 cell count

Objetivo: Describir los patrones radiológicos de afectación pulmonar de la tuberculosis (TB) en pacientes con el virus de la inmunodeficiencia humana (VIH+) y su relación con el índice de linfocitos CD4 en sangre.Material y métodos: Presentamos 44 pacientes VIH+, 24 con CD4 inferior a 200 células/mm3 y 20 con CD4 superior a 200 células/mm3 en los que hemos valorado los hallazgos de la Radiografía (Rx) de tórax comparándolos con los niveles de linfocitos CD4 en sangre. Para la valoración estadística de las diferencias de patrones de presentación entre los grupos A y B se utilizó el test de probabilidad exacta de Fisher.Resultados: 24 pacientes presentaban niveles de linfocitos CD4 en rango menor a 200 células/mm3 (grupo A) y en 20 los niveles eran superiores a 200 células/mm3.Las manifestaciones atípicas son significativamente más frecuentes en los pacientes con un nivel de CD4 inferior a 200 células/mm3 (grupo A) que en los de CD4 superior a 200 células/mm3 (grupo B).Conclusión: En el grupo de pacientes con un mejor estado inmunitario, existe un mayor número de pacientes con patrones pulmonares típicos de TB posprimaria con lesiones cavitarias en lóbulos superiores.En el grupo con inmunidad más deficiente exite un mayor número de enfermos con patrones pulmonares atípicos, más característicos de una TB primaria (AU)

Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults.

PRO 542 (CD4-IgG2) is a recombinant antibody-like fusion protein wherein the Fv portions of both the heavy and light chains of human IgG2 have been replaced with the D1D2 domains of human CD4. Unlike monovalent and divalent CD4-based proteins, tetravalent PRO 542 potently neutralizes diverse primary human immunodeficiency virus (HIV) type 1 isolates. In this phase 1 study, the first evaluation of this compound in humans, HIV-infected adults were treated with a single intravenous infusion of PRO 542 at doses of 0.2-10 mg/kg. PRO 542 was well tolerated, and no dose-limiting toxicities were identified. Area under the concentration-time curve, and peak serum concentrations increased linearly with dose, and a terminal serum half-life of 3-4 days was observed. No patient developed antibodies to PRO 542. Preliminary evidence of antiviral activity was observed as reductions in both plasma HIV RNA and plasma viremia. Sustained antiviral effects may be achieved with repeat dosing with PRO 542.

Phase 1 study of recombinant human CD4-immunoglobulin G therapy of patients with AIDS and AIDS-related complex.

The safety and pharmacokinetics of recombinant CD4-immunoglobulin G (rCD4-IgG) were evaluated in a phase 1 study with dose escalation. A total of 16 patients, 6 with AIDS and 10 with AIDS-related complex, were evaluated at two university-affiliated hospital clinics. rCD4-IgG was administered once weekly for 12 weeks to four patients each at doses of 0.03, 0.1, 0.3, and 1.0 mg/kg of body weight. Dosing was intravenous for two patients in the 1.0-mg/kg dose group and intramuscular for the remaining patients. Dosing was intravenous for two patients in the 1.0-mg/kg dose group and intramuscular for the remaining patients. Pharmacokinetic, toxicity, and immunologic variables were monitored with all patients. Administration of rCD4-IgG was well tolerated, with no important clinical or immunologic toxicities noted. No subjects required dose reduction or discontinuation of therapy due to toxicity. No consistent changes were seen in human immunodeficiency virus antigen levels in serum or CD4 lymphocyte populations. The volume of distribution was small, and compared with that of rCD4, the half-life of the hybrid molecule was markedly prolonged following intramuscular or intravenous administration. The rate and extent of absorption following intramuscular dosing were variable. Intramuscular administration of rCD4-IgG appears to be inferior to intravenous dosing from a pharmacokinetic standpoint, with lower peak concentrations and variable absorption. After intravenous administration, peak concentrations of rCD4-IgG in serum (20 to 24 micrograms/ml) that have shown antiviral activity in vitro against more sensitive clinical isolates of human immunodeficiency virus were achieved. The peak concentrations in serum after intramuscular administration were below these levels. Treatment with rCD4-IgG was well tolerated at the doses administered to patients in this study but did not result in significant changes in CD4 lymphocyte counts or p24 antigen levels in serum.