RESUMEN

HIV-1 reverse transcriptase (RT) genotypes were obtained from 13 patients treated with stavudine. No previously-reported mutations indicative of stavudine resistance were found in these patients and no novel mutations occurred in more than two patients. One patient, treated with stavudine for 1 month and treated previously with zidovudine, zalcitabine and lamivudine, carried a mutation at codon 75 of the RT (V75M). A chimeric virus, including the patient's RT sequence from codon 25 to codon 220, which carried the resistance mutations M41 L, D67N, T69D, K70R, L210W and T215Y in addition to V75M, displayed reduced susceptibility to multiple nucleoside RT inhibitors (NRTIs). Removal of V75M from this RT background resulted in a return of susceptibility to didanosine and lamivudine. Our data are in agreement with previous studies demonstrating the rarity of stavudine resistance mutations in stavudine-treated patients. However, we describe a new set of mutations, found in the RT of a heavily-treated patient, that can confer reduced susceptibility to multiple NRTIs. These results underscore the importance of increased vigilance for possible multiple-drug resistance in patients who have been heavily treated with NRTIs.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral Múltiple , Transcriptasa Inversa del VIH/genética , Mutación , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Estavudina/uso terapéutico , Secuencia de Aminoácidos , Genotipo , Transcriptasa Inversa del VIH/química , Humanos , Datos de Secuencia Molecular

RESUMEN

OBJECTIVES: To compare the antiviral activity and safety of a new protease inhibitor, amprenavir (141W94) in combination with lamivudine and zidovudine, versus lamivudine and zidovudine alone in HIV-1 infected, antiretroviral-naive subjects. DESIGN: Subjects (n=232) with a CD4 T cell count of > or =200 cells/mm3, plasma HIV-1 RNA levels of > or =10000 copies/ml, and < or =4 weeks of prior nucleoside antiretroviral therapy, were stratified according to baseline plasma HIV-1 RNA level (10000-30000; 30000-100000; or >100000 copies/ml). Subjects received double-blind treatment with either 1200 mg amprenavir twice daily in combination with lamivudine (150 mg twice daily) and zidovudine (300 mg twice daily) (amprenavir/lamivudine/zidovudine) or matched placebo, lamivudine and zidovudine for 16 weeks. Thereafter, subjects with confirmed plasma HIV-1 RNA levels of > or =400 copies/ml could add open-label amprenavir or switch to other antiretrovirals and continue treatment for up to a minimum of 48 weeks. The primary endpoint of the study was defined as the proportion of subjects with plasma HIV-1 RNA of <400 copies/ml at 48 weeks. RESULTS: At 48 weeks, a significantly greater proportion of amprenavir/lamivudine/zidovudine subjects had plasma HIV-1 RNA levels <400 copies/ml than lamivudine/ zidovudine subjects in the overall population: 41 versus 3% (intent-to-treat missing equals failure analysis) (P<0.001); 93 versus 42% (as-treated analysis) (P<0.001); and within each of the three randomization strata (P<0.001). Subjects on amprenavir/lamivudine/zidovudine experienced longer time to event (permanent discontinuation of randomized therapy or viral rebound) than those on lamivudine/zidovudine (median of 33 versus 13 weeks; P<0.001). A significantly greater incidence of drug-related nausea, vomiting, rash and oral/perioral paresthesia was observed with amprenavir/lamivudine/zidovudine than with lamivudine/zidovudine. CONCLUSIONS: Amprenavir, in combination with lamivudine and zidovudine, has potent and durable antiviral activity in antiretroviral-naive subjects over 48 weeks. Amprenavir was safe and generally well tolerated.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lamivudine/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Sulfonamidas/uso terapéutico , Zidovudina/uso terapéutico , Adolescente , Adulto , Recuento de Linfocito CD4 , Carbamatos , Quimioterapia Combinada , Femenino , Furanos , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre

RESUMEN

OBJECTIVE: The present study was designed to determine the effect of immune activation, achieved by influenza vaccination, on plasma HIV RNA levels and immunological parameters including CD4 cell levels, antigen-stimulated T-cell function and apoptotic death of peripheral blood mononuclear cells. DESIGN AND METHODS: Thirty-four HIV-infected individuals and nine uninfected controls were immunized with influenza vaccine and blood was collected at weeks 0, 2, 4 and 16. Plasma was isolated and used for HIV RNA and influenza-specific antibody qualifications. CD4 cell counts, activation and maturation markers of T-lymphocyte subsets were determined by flow cytometry. In vitro T-helper responses, spontaneous- and activation-induced cell death assays were also performed. RESULTS: Influenza-specific humoral and cellular immune responses correlated with CD4 count. Only in patients with CD4 counts > 300 x 10(6)/l there was a modest increase in T-cell responses to influenza virus, which was less than control subjects, observed after vaccination. Immunization had no significant effect on CD4 counts or plasma viral levels in the HIV-positive patients. Baseline apoptosis inversely correlated with CD4 counts and directly correlated with viral load. Activation-induced apoptosis did not change appreciably after vaccination and spontaneous apoptosis increased only in the < 300 CD4 group. CONCLUSION: These results indicate that immune stimulation resulting from influenza vaccination did not significantly change the levels of plasma virus, CD4 cell counts, or activation-induced apoptosis in HIV-infected individuals, although an increase in the T-cell response to influenza and spontaneous apoptosis was observed in the > 300 and < 300 CD4 groups, respectively.

Asunto(s)

Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1 , Vacunas contra la Influenza/administración & dosificación , Anticuerpos Antivirales/inmunología , Apoptosis , Recuento de Linfocito CD4 , Citometría de Flujo , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Activación de Linfocitos , ARN Viral/sangre , Linfocitos T Colaboradores-Inductores/citología , Linfocitos T Colaboradores-Inductores/inmunología , Vacunación

RESUMEN

We performed a pilot study that examined the clinical and pharmacokinetic interactions between zidovudine (ZDV) and a pyridinone derivative, L-697-661. The results indicate that the drugs were well tolerated, with no important pharmacokinetic interactions, when administered concomitantly for as long as 8 weeks. Although the number of study participants was small, we noted rapid emergence of resistance to L-697,661 among ZDV-naive study subjects who were administered L-697,661 as monotherapy but did not observe isolates of human immunodeficiency virus type 1 (HIV-1) resistant to L-697,661 among those who were administered concomitant ZDV. These results suggest a potential interaction between development of resistance to L-697,661 and ZDV. Although the clinical development of L-697,661 has been halted, our results support the need for further studies to test whether specific interactions among antiretroviral agents administered in combination and the molecular target can delay the emergence of isolates that exhibit resistance to all drugs in the regimen.

Asunto(s)

Antivirales/uso terapéutico , Benzoxazoles/uso terapéutico , Seropositividad para VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Piridonas/uso terapéutico , Zidovudina/uso terapéutico , Adulto , Antipirina , Antivirales/farmacocinética , Antivirales/farmacología , Secuencia de Bases , Benzoxazoles/farmacocinética , Benzoxazoles/farmacología , Estudios Cruzados , Cartilla de ADN/química , ADN Viral/química , Interacciones Farmacológicas , Farmacorresistencia Microbiana , Quimioterapia Combinada , Femenino , Genes pol/genética , Genotipo , Seropositividad para VIH/metabolismo , VIH-1/genética , Humanos , Masculino , Datos de Secuencia Molecular , Proyectos Piloto , Piridonas/farmacocinética , Piridonas/farmacología , Inhibidores de la Transcriptasa Inversa/farmacocinética , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Zidovudina/farmacocinética , Zidovudina/farmacología

RESUMEN

The study objective was to obtain preliminary information regarding the safety and efficacy of amphotericin B (AmB) lipid complex (ABLC) in the treatment of AIDS-associated cryptococcal meningitis. Of 55 patients randomly assigned to 6 weeks of therapy with ABLC (1.2-5.0 mg/[kg.d], with ascending doses for three sequential cohorts) or AmB (0.7-1.2 mg/[kg.d]), 46 received > or = 12 doses. Transfusion requirements, mean decreases in hemoglobin level, and mean increases in creatinine level were significantly greater with AmB than with ABLC. The total number of adverse events, infusion-related events, and occurrences of hypomagnesemia and hypokalemia associated with each form of therapy were similar. Among 21 recipients of ABLC at a dosage of 5 mg/kg (daily for 2 weeks and then thrice weekly for 4 weeks), symptoms and signs resolved for 18 (86%). Of those receiving > or = 12 doses of ABLC, cultures converted to negative for 8 (42%), were undeterminable for 3 (16%), and remained positive for 8 (42%) despite resolution of symptoms. Although preliminary, these data suggest ABLC has significant activity in patients with AIDS-associated cryptococcal meningitis. Because this formulation has less hematologic and renal toxicity than does AmB, further evaluation of ABLC is warranted.

Asunto(s)

Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Meningitis Criptocócica/tratamiento farmacológico , Fosfatidilcolinas/uso terapéutico , Fosfatidilgliceroles/uso terapéutico , Adulto , Anfotericina B/administración & dosificación , Anfotericina B/efectos adversos , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Estudios de Cohortes , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosfatidilcolinas/administración & dosificación , Fosfatidilcolinas/efectos adversos , Fosfatidilgliceroles/administración & dosificación , Fosfatidilgliceroles/efectos adversos

RESUMEN

Changes in viral load have been reported to reflect disease progression or response to therapy; however, the stability of HIV DNA levels in HIV-infected individuals has not been extensively studied. Cellular HIV DNA levels in infected individuals were evaluated over a short time period to determine degree of variability as well as any correlation with other measurements of virus load or immune status. Peripheral blood mononuclear cells (PBMC) were obtained several times over 1 month from 32 asymptomatic or symptomatic non-AIDS, HIV-infected individuals currently on AZT therapy. PCR amplification of the HIV gag region was performed with DNA from PBMC lysates and the PCR amplified products quantitated by liquid phase hybridization. HIV DNA levels in the majority of the patients were relatively stable, with 26 of 32 persons having less than threefold change. Changes over the study period were both positive and negative, and the median change in HIV DNA levels was 68.6%. These changes were found to positively correlate with fluctuations in plasma p24 levels. In contrast, no correlations were found with other measurements of immune system activity, including changes in CD4 number, CD4 percent, and beta 2-microglobulin when compared with provirus changes. This study shows that levels of HIV DNA can be relatively stable over short periods in most non-AIDS, HIV-infected persons.

Asunto(s)

Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Provirus/aislamiento & purificación , Secuencia de Bases , Cartilla de ADN , ADN Viral/aislamiento & purificación , Progresión de la Enfermedad , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/sangre , Seropositividad para VIH/virología , VIH-1/genética , Humanos , Leucocitos Mononucleares/virología , Datos de Secuencia Molecular , Provirus/genética , Factores de Tiempo , Microglobulina beta-2/análisis

RESUMEN

Deep fungal infections of the breast have been reported infrequently. These infections are usually discovered during an evaluation of a breast mass for neoplasia. We report a case of cryptococcal infection of the breast that presented as a mass lesion and was successfully treated with a combination of surgical excision and fluconazole and summarize eight additional cases from the literature. Because of the risk of disseminated and recurrent cryptococcal infection after surgical treatment alone, evaluation for disseminated disease and systemic antifungal therapy for cryptococcal mastitis are suggested.

Asunto(s)

Criptococosis/diagnóstico , Mastitis/diagnóstico , Antifúngicos/uso terapéutico , Antígenos Fúngicos/sangre , Terapia Combinada , Criptococosis/tratamiento farmacológico , Criptococosis/cirugía , Cryptococcus neoformans/inmunología , Cryptococcus neoformans/aislamiento & purificación , Femenino , Fluconazol/uso terapéutico , Humanos , Mastitis/tratamiento farmacológico , Mastitis/cirugía , Persona de Mediana Edad

RESUMEN

Herpes simplex virus (HSV) infections are very common in the general population and can be treated with the nucleoside analogue acyclovir. Acyclovir is initially phosphorylated intracellularly in HSV-infected cells by a viral-specific thymidine kinase to acyclovir-monophosphate. The monophosphate is subsequently di- and triphosphorylated by host cellular kinases to the active form of the drug, which inhibits HSV DNA polymerase and incorporates into the elongating viral DNA and causes chain termination. Acyclovir resistance has been increasingly described and is caused by mutations in either the thymidine kinase or the DNA polymerase genes. These mutations result in decreased or absent HSV thymidine kinase production, altered affinity of the thymidine kinase for acyclovir-triphosphate, or altered affinity of the HSV DNA polymerase for acyclovir-triphosphate. Thymidine kinase deficiency accounts for approximately 95% of acyclovir-resistant isolates. Clinical disease due to acyclovir-resistant HSV occurs primarily in immunocompromised patients and is usually characterized by a chronic, progressive ulcerative mucocutaneous disease with prolonged shedding of virus. Several large surveys have been done in an effort to determine the incidence of in vitro and clinical acyclovir resistance. Among immunocompetent hosts, even those who have received > or = 6 years of continuous acyclovir, the prevalence of acyclovir-resistant isolates has remained stable at approximately 3%. Only three cases of clinical resistance of HSV to acyclovir have been reported. However, the incidence in immunocompromised patients, particularly those with AIDS and those who have had bone marrow transplants, is increasing. Transmission of acyclovir-resistant isolates from person to person has not been documented, but due to the increased use of acyclovir and newer drugs, such as famciclovir, there is great concern that this transmission might occur in the future. Continued surveillance in both immunocompetent and immunocompromised hosts for the development of clinical acyclovir-resistant HSV disease is necessary.

Asunto(s)

Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Herpes Simple/tratamiento farmacológico , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Aciclovir/farmacología , Antivirales/farmacología , Farmacorresistencia Microbiana , Herpes Simple/epidemiología , Herpes Simple/patología , Humanos , Huésped Inmunocomprometido , Estados Unidos/epidemiología

RESUMEN

To further characterize the natural history of HIV infection in women in the antiretroviral era, we performed a longitudinal, descriptive analysis of demographic features, clinical characteristics, patterns of antiretroviral and prophylactic therapy, disease progression, and survival in a cohort of women followed at a university medical center from 1986 to 1992. Eighty-two women (39 white [non-Hispanic], 33 African-American, 10 Hispanic) were followed for a median of 13 months (range 3-61 months). Sixty-two women received antiretroviral therapy, 34 through participation in a clinical trial. Candida esophagitis and Pneumocystis carinii pneumonia were the most common AIDS-defining conditions, accounting for 77% of all initial AIDS-defining diagnoses. Gynecologic complications affected 34 women (41%) and included recurrent Candida vaginitis in 26, abnormal PAP smears/cervical intraepithelial neoplasia in 10, and recurrent genital herpes simplex virus disease in seven. Median survival (Kaplan-Meier) from the time of HIV serodiagnosis was > 59 months; median survival following an AIDS diagnosis was 27 months. No survival differences were detected based on race, insurance status, or mode of HIV transmission. Women who participated in antiretroviral therapy clinical trials had a statistically significantly longer duration of survival compared with nonparticipants. Candida infections and gynecologic diseases were common in this population. Overall survival was similar to that reported for men.

Asunto(s)

Infecciones por VIH/epidemiología , Adulto , Anciano , Recuento de Linfocito CD4 , Candidiasis Vulvovaginal/complicaciones , Chicago/epidemiología , Ensayos Clínicos como Asunto/estadística & datos numéricos , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Enfermedades de los Genitales Femeninos/complicaciones , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Neumonía por Pneumocystis/prevención & control , Estudios Prospectivos , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia

RESUMEN

We performed antifungal susceptibility tests with cilofungin (LY121019), amphotericin B, and flucytosine against 38 strains of yeasts from patients with esophagitis or fungemia either before, during, or after treatment with cilofungin. Tests were performed using a macrobroth dilution method similar to that proposed by the National Committee for Clinical Laboratory Standards (M27-P) and two microbroth methods. For cilofungin and amphotericin B, minimum inhibitory concentrations from microbroth tests using Antibiotic Medium 3 (AM3) were systematically lower than results from the other two methods that utilized RPMI-1640 medium (RPMI). AM3 did not provide any greater degree of in vitro correlation with clinical results than did RPMI. We conclude that cilofungin and possibly other congeners of the echinocandin class of antifungal agents can effectively be studied using the proposed National Committee for Clinical Laboratory Standards method.

Asunto(s)

Anfotericina B/farmacología , Candida/efectos de los fármacos , Flucitosina/farmacología , Pruebas de Sensibilidad Microbiana/métodos , Péptidos Cíclicos/farmacología , Candidiasis/microbiología , Farmacorresistencia Microbiana , Equinocandinas , Esofagitis/microbiología , Estudios de Evaluación como Asunto , Fungemia/microbiología , Humanos , Estudios Prospectivos

RESUMEN

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)

Asunto(s)

1-Desoxinojirimicina/análogos & derivados , Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Zidovudina/uso terapéutico , 1-Desoxinojirimicina/efectos adversos , 1-Desoxinojirimicina/farmacocinética , 1-Desoxinojirimicina/uso terapéutico , Adulto , Antivirales/efectos adversos , Antivirales/farmacocinética , Linfocitos T CD4-Positivos/citología , Diarrea/inducido químicamente , Método Doble Ciego , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/inmunología , VIH-1/efectos de los fármacos , VIH-1/genética , Hemoglobinas/análisis , Humanos , Recuento de Leucocitos , Masculino , Neutrófilos/efectos de los fármacos , Parestesia/inducido químicamente , ARN Viral/sangre , Zidovudina/efectos adversos , Zidovudina/farmacocinética , Microglobulina beta-2/análisis

RESUMEN

Candida krusei has recently been increasingly recognized as a pathogen in immunocompromised patients with malignancies. We report four immunocompromised patients with C. krusei fungemia and review the literature. Including our 4 cases, 62 cases of C. krusei fungemia were identified in the literature. Detailed information was available for only 25 patients. The clinical features of patients with C. krusei fungemia are similar to those reported for Candida tropicalis. Most patients were neutropenic and more than one half of the patients had received antifungal therapy and had evidence of gastrointestinal mucosal breakdown before the development of C. krusei fungemia. The overall mortality was 48%. Patients treated with regimens containing amphotericin B had improved survival over patients who received no therapy. Favorable response rates were higher in patients receiving high-dose amphotericin B or high-dose amphotericin B plus flucytosine when compared to patients treated with low-dose amphotericin B.

Asunto(s)

Candidiasis , Fungemia , Adulto , Anciano , Candidiasis/diagnóstico , Candidiasis/tratamiento farmacológico , Candidiasis/inmunología , Femenino , Fungemia/diagnóstico , Fungemia/tratamiento farmacológico , Fungemia/inmunología , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad

RESUMEN

OBJECTIVE: To determine whether alternating regimens consisting of zidovudine and 2',3'-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. DESIGN: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. SETTING: Outpatient clinics of 12 AIDS Clinical Trials Units. PATIENTS: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigenemia (> or = 70 pg/mL). INTERVENTION: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. MEASUREMENTS: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). RESULTS: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P < 0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high rates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. CONCLUSIONS: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.

Asunto(s)

Complejo Relacionado con el SIDA/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Zalcitabina/administración & dosificación , Zidovudina/administración & dosificación , Linfocitos T CD4-Positivos/efectos de los fármacos , Esquema de Medicación , Quimioterapia Combinada , Femenino , Proteína p24 del Núcleo del VIH/efectos de los fármacos , Enfermedades Hematológicas/inducido químicamente , Humanos , Recuento de Leucocitos , Masculino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Aumento de Peso/efectos de los fármacos , Zalcitabina/efectos adversos , Zidovudina/efectos adversos

RESUMEN

To further characterize the clinical features, response to therapy, and outcome of Pneumocystis carinii choroiditis in patients with AIDS, we retrospectively reviewed the course of choroiditis for eight patients identified from two institutions through April 1991. Seven patients had prior Pneumocystis carinii pneumonia and had received aerosolized pentamidine prophylaxis for a median of 10 months; one patient had no prior history of pneumonia or prophylaxis. The median CD4+ lymphocyte count for six patients was 11 cells/mm3. Choroiditis was a preterminal diagnosis for three patients--two with associated disseminated pneumocystosis. Ocular manifestations improved or resolved with therapy for five of the six treated patients. All five subsequently received prophylaxis with dapsone (n = 2), dapsone/trimethoprim (n = 2), or aerosolized pentamidine (n = 1). Choroiditis recurred at 15 months in the one patient receiving aerosolized pentamidine. The median survival from time of diagnosis was 44 weeks. A literature review including an additional 40 cases support the conclusions that (a) Pneumocystis choroiditis is a rare complication of advanced HIV disease, occurring often in the context of systemic pneumocystosis; (b) ocular signs and symptoms may improve or resolve with specific antipneumocystis therapy; and (c) relapse may occur, particularly in those not receiving systemic prophylaxis.

Asunto(s)

Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/fisiopatología , Coroiditis/fisiopatología , Pentamidina/uso terapéutico , Infecciones por Pneumocystis/tratamiento farmacológico , Infecciones por Pneumocystis/fisiopatología , Infecciones Oportunistas Relacionadas con el SIDA/patología , Adulto , Coroiditis/tratamiento farmacológico , Coroiditis/patología , Ojo/microbiología , Ojo/patología , Femenino , Humanos , Masculino , Pneumocystis/aislamiento & purificación , Infecciones por Pneumocystis/patología , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

Great strides have been made in the therapy of human immunodeficiency virus (HIV) infection. Currently approved drugs include zidovudine and didanosine. A third drug, dideoxycytidine (zalcitibine), has recently been filed for approval with the Food and Drug Administration. All these drugs work through inhibition of the reverse transcriptase enzyme. Zidovudine is the only drug that has shown clinical efficacy against HIV. Treatment of patients with advanced HIV disease (i.e., acquired immune deficiency syndrome [AIDS] or symptomatic infection with < 200 CD4+ lymphocytes per mm3), results in a prolongation and improved quality of life. Zidovudine is the only antiretroviral agent approved for the treatment of asymptomatic patients. Early intervention with zidovudine has been shown to delay progression to AIDS when patients' CD4+ lymphocyte counts decline to less than 500/mm3, irrespective of clinical signs or symptoms of HIV infection. Didanosine is currently indicated for the treatment of patients with advanced HIV disease who are intolerant to or failing zidovudine therapy. The major toxicity of zidovudine is bone marrow suppression with anemia and granulocytopenia (which occurs in from 1% to 45% of patients, depending on the clinical stage of disease and the dose of the drug). Didanosine and zalcitibine have both been associated with a severe peripheral neuropathy, which is generally reversible on cessation of the drug. In addition, didanosine has been implicated as a cause of pancreatitis that has been fatal in a small percentage of cases. The toxicities of didanosine and zalcitibine range from 1% to 10%, depending on dose, duration of therapy, and the presence of underlying HIV-related peripheral neuropathy or a previous history of pancreatitis. The clinical hallmark of HIV infection is the development of opportunistic infections and malignancies, which are a consequence of the profound immunodeficiency. The risk of an opportunistic infection increases significantly as the T-helper lymphocyte count declines to less than 20%, or 200 to 250/mm3. The spectrum of opportunistic infections ranges from viruses to protozoa. Patients with advanced HIV disease are also at increased risk of infection with nonopportunistic, community-acquired pathogens. Primary and secondary prophylaxis against the most common AIDS-defining opportunistic infection, Pneumocystis carinii pneumonia, is now recommended. Studies are currently underway to determine the efficacy of prophylaxis against other opportunistic pathogens. Treatment of opportunistic infections associated with AIDS has improved significantly over the past 5 years as new drugs and combination regimens of antimicrobials have been developed.(ABSTRACT TRUNCATED AT 400 WORDS)

Asunto(s)

Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Humanos

RESUMEN

Acquired immunodeficiency syndrome (AIDS) is caused by infection with a pathogenic human retrovirus known as human immunodeficiency virus (HIV). Approximately 1 million people are currently infected with HIV in the United States, with 8 to 10 million infected individuals worldwide. The virus is transmitted predominantly through genital sexual contact, although orogenital spread has been rarely reported. Heterosexual transmission has been most common in the Third World, whereas male homosexual transmission has predominated in the United States and western Europe. Transmission through homosexual contact has been steadily declining over the past 5 years as transmission through illicit intravenous drug use and promiscuous unprotected heterosexual activity has increased. Sexually transmitted diseases that cause inflammatory or ulcerative lesions of the genital tract act as important cofactors in increasing the risk of transmission through sexual contact. Perinatal transmission of HIV occurs in approximately 30% of infants born to infected mothers. Transmission to infants through breast-feeding has also been documented. Health care workers have been infected with HIV through accidental high-risk percutaneous or mucous membrane exposures, albeit at a low transmission rate of 0.3%. Infection of patients by infected health care professionals is a rare event, having been reported only once in 10 years of the epidemic. Infection with HIV results in a chronic lifelong infection. The major targets for HIV are CD4+ T-helper lymphocytes and cells of monocyte/macrophage lineage. Infection of the T-helper lymphocyte ultimately results in the death of the cell. Over time (measured in years), a progressive destruction of the T-helper lymphocyte population occurs, which results in profound immune suppression. Infection of monocytes/macrophages is not cidal, but these cells do have functional alterations as a result of the infection, which may contribute to the immune deficiency. In addition, chronically infected tissue macrophages may act as an important reservoir for HIV, particularly in the central nervous system. Infection of the T-helper lymphocytes and monocytes/macrophages is mediated through attachment of HIV through a specific binding interaction between CD4 expressed in the plasma membrane of these cells and a surface glycoprotein on the virus, gp120. Once the virus nucleocapsid (core particle) enters the cytoplasm of the target cell, the viral RNA genome is reverse transcribed by a reverse transcriptase enzyme into proviral DNA. This proviral DNA migrates into the nucleus where it integrates into the host cellular genome, which results in a chronically infected cell.(ABSTRACT TRUNCATED AT 400 WORDS)

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/etiología , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Síndrome de Inmunodeficiencia Adquirida/transmisión , Femenino , VIH/clasificación , VIH/patogenicidad , Seropositividad para VIH/diagnóstico , Personal de Salud , Humanos , Masculino , Tamizaje Masivo/métodos , Enfermedades Profesionales/prevención & control , Embarazo

Asunto(s)

Didanosina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Zidovudina/efectos adversos , Adulto , Tolerancia a Medicamentos , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/complicaciones , Blastomicosis/complicaciones , Infecciones Oportunistas/complicaciones , Adulto , Antifúngicos/uso terapéutico , Blastomicosis/diagnóstico , Blastomicosis/tratamiento farmacológico , Blastomicosis/mortalidad , Humanos , Enfermedades Pulmonares Fúngicas/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia

Asunto(s)

Criptococosis/tratamiento farmacológico , Fluconazol/uso terapéutico , Infecciones por VIH/complicaciones , Histoplasmosis/complicaciones , Meningitis/tratamiento farmacológico , Criptococosis/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Meningitis/complicaciones , Persona de Mediana Edad

RESUMEN

We retrospectively analyzed data from 75 hospitalized patients with a first episode of Pneumocystis carinii pneumonia to compare the ability of four parameters, including admission serum albumin, serum lactate dehydrogenase (LDH), alveolar-arterial oxygen gradient, and the APACHE II score, to predict mortality and response to initial antipneumocystis therapy. The eight patients who died due to pneumocystosis and the 12 who failed initial antipneumocystis therapy had significantly higher admission mean APACHE II scores and serum LDH levels and lower mean serum albumin levels than did the 65 who survived and the 61 who responded to initial therapy (p less than 0.05 for each). Differences in mean alveolar-arterial oxygen gradients were not statistically significant with respect to survival or response to initial therapy. In a stepwise discriminant analysis of parameters associated with mortality, APACHE II score and LDH level were statistically significant (p less than 0.0001 for each). In a stepwise discriminant analysis of parameters associated with response to initial therapy, APACHE II score and LDH level were again statistically significant (p less than 0.0001, respectively). The addition of the alveolar-arterial oxygen gradient and serum albumin level did not further increase the predictive ability of the discriminant analyses. When analyzed alone, neither the alveolar-arterial oxygen gradient nor the serum albumin were statistically significant in each discriminant analysis. The APACHE II score combined with the serum LDH may be more useful than other parameters, singly or combined, to more closely match patients with regard to severity of illness due to first episode Pneumocystis carinii pneumonia when comparing experimental new therapies with standard agents.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/complicaciones , L-Lactato Deshidrogenasa/sangre , Infecciones Oportunistas/mortalidad , Neumonía por Pneumocystis/mortalidad , Índice de Severidad de la Enfermedad , Adulto , Femenino , Humanos , Masculino , Infecciones Oportunistas/complicaciones , Infecciones Oportunistas/tratamiento farmacológico , Neumonía por Pneumocystis/complicaciones , Neumonía por Pneumocystis/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Albúmina Sérica/análisis