摘要:

Summary:HIV is the greatest single risk factor for the development of tuberculosis. Diseases caused byM. tuberculosisand mycobacteria are the most common opportunistic infections in HIV-infected persons, which may stem from a functional defect of the CD4+T-cell-mediated killing of macrophages harboring mycobacteria. Our objective was to investigate theM. tuberculosis- andM. avium-specific cytotoxic capacity of T cells from healthy, bacille Calmette-Guérin-vaccinated, HIV-seropositive individuals. Blood mononuclear cells were obtained from 10 healthy HIV-seropositive and 10 healthy seronegative persons with no history of previous or active mycobacterial infection. Antigen-specific killing of macrophages presenting mycobacterial antigens (purified protein derivative orM. aviumculture filtrate) was conducted. The phenotype of the killer cells was determined by a fluorescence-activated cell sorter after antigen stimulation and by using purified CD4+and CD8+cell subsets. Substantial, but reduced antigen-specific cytotoxicity was observed in patients with asymptomatic HIV infection. The immunological dysfunction leading to reduced cytotoxic activity in healthy HIV-seropositive subjects could not be explained by a defect in the cytotoxic capacity of the individual CD4+lymphocyte after antigen stimulation, and it could not be explained by a reduction in the total number of CD4+cells before antigen stimulation. The antigen-specific cytotoxic activity was, however, closely related to the ability of the CD4+T cells to respond to mycobacterial antigens. The immunological dysfunction leading to reduced mycobacterial-specific cytotoxic activity in healthy HIV-seropositive subjects is caused either by a reduction in the number of antigen-responsive CD4+T cells (memory) or by an impairment of their ability to respond to antigenic stimuli.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The transmembrane glycoproteins of all retroviruses contain a conserved region composed of a leucine zipper, an immunosuppressive domain, and an immunodominant Cys-Cys loop. The amino acid sequence of the immunosuppressive domain of gp41 of human immunodeficiency virus type 1 (HIV-1; amino acids 583-599) is closely related, but not identical, to the immunosuppressive domains of type C and D retroviruses. A synthetic peptide corresponding to the immunosuppressive domain of HIV-1 (immunosuppressive peptide, ISU-peptide) inhibits mitogen and lymphokine stimulation of T lymphocytes. It is interspecies reactive and inhibits both human and mouse lymphocytes. The inhibitory effect is not based on direct cytotoxicity and the peptide is immunosuppressive only when conjugated to a carrier protein. The ISU-peptide of HIV-1 also inhibits B lymphocyte stimulation by the B cell mitogen lipopolysaccharide and by specific antibodies against δ and μ chains of cell surface immunoglobulins. These data suggest that the immunosuppressive domain of gp41 may play an important role in the immunopathogenesis of AIDS.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The antiretroviral efficacy and hematotoxicity of ribavirin, a guanosine analogue, have been evaluated in mice infected with the LP-BM5 virus pool [murine acquired immunodeficiency syndrome (MAIDS) model]. Doses ranging from 6.25 to 200 mg/kg/day were injected intraperitoneally twice a day for 6 weeks to infected mice. Drug treatment induced a significant protection against splenomegaly and lymphadenopathy at doses ≥25 mg/kg. Moreover, doses starting at 50 mg/kg protected against hypergammaglobulinemia, minimized the loss of spleen CD8+T cells, and reconstituted the capacity of splenocytes to proliferate in response to concanavalin A. The spleen and cervical lymph node architectures were protected, and a reduction in the emergence of germinal centers was observed at 50 mg/kg ribavirin. Hematotoxicity appeared at doses ≥50 mg/kg ribavirin, and severe anemia was predominant only at doses of 100 and 200 mg/kg. This study shows that ribavirin protects mice against the effects resulting from retrovirus infection at doses of ≥50 mg/kg in a MAIDS model and induces severe hematotoxicity at doses ≥100 mg/kg.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Although the efficacy of switching from zidovudine (AZT) to didanosine (ddI) has already been evaluated in controlled studies, prior investigations were not specifically designed to evaluate this issue in patients with acquired immune deficiency syndrome (AIDS). This open, randomized, multicenter study (ISS 901) was designed to evaluate the clinical benefit in patients with AIDS of switching to ddI after 6-18 months of AZT and no major intolerance. Patients were randomized to continue AZT, maintaining the current dosage at randomization (n= 79), or to receive ddI (n= 80) at the dosage of 375 mg and 250 mg b.i.d. for body weight >60 and ≤60 kg, respectively. Primary efficacy measures were survival and time to new AIDS-defining events, analyzed by the intent-to-treat approach. The two groups were comparable for baseline characteristics, follow-up (15 months), and time spent on allocated treatment. At the end of the study, 104 patients (48 AZT, 56 ddI) had died and 90 had at least one new AIDS-defining event (44 AZT, 46 ddI). Kaplan-Meier estimates of survival and of time to first new AIDS-defining event showed no differences between the treatment groups. No differences were detected in other efficacy measurements (p24 antigenemia, CD4+ count, Karnofsky score, and body weight), occurrence of severe toxicities, and treatment modifications. Pancreatitis occurred only in ddI-treated patients (6%). In our population of patients with advanced disease, switching from AZT to ddI did not produce apparent benefits, suggesting that application of this strategy earlier in the course of human immunodeficiency virus disease should be considered.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:To determine whether daily use of nystatin pastilles can prevent initial outbreak or recurrence of oral candidiasis in HIV-infected patients and to identify factors associated with outbreaks during 20-week follow-up, a randomized, double-blind, placebo-controlled clinical trial was conducted. Subjects were 128 HIV-infected men (aged 27-60 years) who either had had no documented episode of oral candidiasis in the previous year or had been clinically clear of oral candidiasis for at least 72 h before randomization. Study arms were two placebo pastilles, one nystatin (200,000 U) and one placebo pastille, or two nystatin pastilles daily for 20 weeks. The main outcome measure was time to oral candidiasis, as determined by potassium hydroxide (KOH) smear and fungal culture. A multivariate proportional hazards model showed that four factors were significant (p< 0.001) in predicting time to oral candidiasis: nystatin treatment (hazard ratio 0.59), history of oral candidiasis (3.58),Candida albicanscarriage (2.79), and CD4 count at randomization (0.65). In this small group of subjects, nystatin appeared to be effective in delaying onset of oral candidiasis. Patients with CD4 counts <200 who are carriers ofC. albicansand have a history of oral candidiasis may be most likely to benefit from antifungal prophylaxis.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Clinically significant methemoglobinemia can develop as a result of medications. Although dapsone and primaquine are known to produce methemoglobinemia in susceptible individuals, methemoglobinemia has been reported only rarely in the human immunodeficiency virus (HIV) population. We describe five cases of methemoglobinemia caused by either primaquine or dapsone alone or in combination. The initial methemoglobin level ranged from 15.3% in the patient whose methemoglobinemia was caused by primaquine alone to 33.1%. Five patients developed symptomatic methemoglobinemia requiring hospitalization for 1 to 12 days. Two cases resulted from intentional overdoses of dapsone, and three developed within several days of commencing primaquine while dapsone remained present in the bloodstream. The four severe cases required intravenous methylene blue, supplemental oxygen, plus erythrocyte transfusions, whereas the mild case responded to oxygen therapy plus discontinuation of the precipitating drugs. Blood gases and pulse oximetry do not aid in the diagnosis, which requires cooximetry. Our study indicates that dapsone and primaquine alone or in combination can produce clinically significant methemoglobinemia in HIV-infected individuals, either in the setting of an overdose or when primaquine is instituted before dapsone has been cleared from the bloodstream.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Previous studies of asymptomatic human immunodeficiency virus (HIV) infection have shown that serum levels of soluble tumor necrosis factor receptors (sTNFR) are good predictors of disease progression and clinical outcome during zidovudine (ZDV) therapy. The present study of symptomatic HIV infection was designed to evaluate whether sTNFR p55 and p75 at weeks 0 (pretreatment) and 24 and 48 are predictors of death ≤3 years after the start of ZDV 1,000 mg alone or combined with low-dose interferon-α (ZDV 500 mg + IFN-α 3 MIU three times weekly). CD4+T-cell numbers and serum neopterin were analyzed in a similar way. Forty previously untreated symptomatic HIV-infected persons with CD4+T-cell numbers ≥150 × 106/L were included. At baseline, in the nonsurvivor group, mean age (42.1 vs. 34.4 years,p= 0.002) and neopterin (24.7 vs. 18.0 nmol/L,p= 0.02) were higher, whereas mean CD4+T-cell counts (202 vs. 295 × 106/L,p= 0.02) were lower than in the survivors. All analyses were adjusted for age. For the pretreatment marker values, a significant relative risk (RR) for death was noted only in the univariate analysis for sTNFR-p55 > 1.7 ng/ml [RR 3.1; 95% confidence interval (CI) 1.1-8.8;p= 0.04]. During therapy, CD4+counts <200 × 106/L at week 24 and 48 and neopterin >20 nmol/ml at week 48 were independent predictors of survival in the uni- and multivariate analysis. Marker values relative to baseline were not predictive. sTNFR-p55 and p75 were of little use as surrogate markers for clinical efficacy during ZDV-containing drug regimens in symptomatic HIV-infected patients with CD4+counts 150 × 106/L.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:To assess whether HIV infection is associated with menstrual abnormalities in HIV-infected women without AIDS, we evaluated 248 premenopausal HIV-infected women without AIDS and 82 HIV-negative women. Detailed medical, drug use, and menstrual histories (using menstrual calendars) were obtained. Complete physical and pelvic examinations and CD4 counts were performed. HIV-infected women were more likely to experience intervals >6 weeks without menstrual bleeding [8 vs. 0%, odds ratio (OR) = 10.8, 95% confidence interval (CI) 1.8-1,000) and amenorrhea >3 months (5 vs. 0%, OR = 7.1, 95% CI 1.1-1,000) (after adjustment for drug use, age, and race). Premenstrual breast swelling (p= 0.01), tenderness (p= 0.01), and dysmenorrhea (p= 0.04) were less common in HIV-infected women. There were no differences in intermenstrual bleeding or irregular menstrual cycles. Among HIV-infected women, only a past history of substance abuse was significantly associated with menstrual irregularities in a logistic regression model adjusting for age, current and past drug use, alcohol use, cigarette smoking, CD4 count, and category B conditions [1993 Centers for Disease Control (CDC) classification system]. The increase in amenorrhea (>3 months) and in menstrual cycle intervals >6 weeks and the lower rates of premenstrual breast symptoms in HIV-positive women suggest the possibility of disturbances in menstrual function that do not appear to be attributable to clinically apparent secondary complications of HIV. Changes in menstrual function were also significantly associated with a past history of, but not current, substance abuse, suggesting the possibility that socioeconomic factors rather than biologic effects of drugs may be responsible.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Measuring the incidence of the human immunodeficiency virus (HIV) is of vital importance but can be difficult and costly. We compared HIV-1 incidence measured directly from prospective cohort studies with rates derived from a method using the prevalence of HIV-1 antibody-negative, p24-antigen-positive individuals. Male and female commercial sex workers (CSWs) were enrolled and followed in separate cohort studies in northern Thailand between 1989 and 1994, and HIV incidence was measured by prospective follow-up of individuals seronegative at baseline. In 1991-1992 cross-sectional serosurveys were done among male and female CSWs in the same region; all HIV-1 antibody-negative subjects in these surveys were tested for p24 antigenemia. HIV incidence was estimated using the prevalence of p24 antigen and a model based on the mean duration of p24 antigenemia before HIV antibody detection. The cohort studies showed high initial incidence rates—23.8/100 person-years (PY) among female CSWs and 11.9/100 PY among male CSWs—but poor compliance with prospective follow-up. Subjects lost to follow-up appeared to be at greater risk of HIV seroconversion than those retained. The p24 antigen method estimate among female CSWs, 25.4%/year, was quite similar to the initial incidence rate found in the cohort. The estimate by the p24 antigen method was higher, 19.9%/year, among male CSWs than that measured prospectively. In populations with high rates of HIV transmission and in whom long-term follow-up is incomplete, estimates of incidence using p24 antigen prevalence among antibody-negative subjects can give useful and economical estimates of HIV incidence and allow for estimates of whether the incidence rates are similar in subjects successfully followed and those lost to follow-up.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Our objective was to estimate HIV seroconversion rates among commercial sex workers (CSWs) between 1990 and 1991 and to identify the behavioral, demographic, and reproductive determinants of these rates. This study has a prospective (n = 240 with 15 cases) and a cross-sectional component (n = 271 with 34 cases). In November 1990, HIV-negative female CSWs from 24 brothels in Khon Kaen city were interviewed and were followed prospectively for up to 1 year. In March, June, and September 1991, additional HIV-negative CSWs were enrolled and prospectively followed. HIV seroconversion rates were calculated, and the Cox regression model was used to estimate the relative risks of HIV seroconversion from demographic, sexual practice, and reproductive factors, adjusted for the effects of the others, among 232 of the 240 without missing data. Seroprevalence rates were also calculated for the 271 participants enrolled between March and December 1991, and relative risks of HIV seroprevalence were calculated for demographic, sexual practice, and reproductive risk factors among 184 of the 271 without missing data. The average seroprevalence was 12.5% (95% confidence interval 9.6-15.4%). With 1,947 person-months of observation obtained from 240 participants who were uninfected at baseline and seen at least twice during the course of the study, the cumulative incidence of HIV seroconversion between November 1990 and December 1991 was 9.4% (95% confidence interval 5.4-13.4%), and the average incidence rate of HIV seroconversion was 9.2 per 100 person-years (95% confidence interval 4.6-13.9 per 100 person-years). In the multivariate analysis, later date of enrollment into the study, having <3 months experience as a CSW, and use of injectable contraceptives were the only risk factors that remained significant, with relative risks of 2.1 (95% confidence interval 1.2-3.7) for enrollment 3 months later, 3.8 (95% confidence interval 1.0-14.4) for <3 months experience as a CSW versus >3 months experience, and 3.4 (95% confidence interval 1.2-13.2) for use of injectable contraceptives. In multivariate analysis of the cross-sectional data with 184 participants, of whom 21 were HIV seropositive, risk of HIV seropositivity increased significantly with current syphilis infection (odds ratio 5.8, 95% confidence interval 1.1-31.0). The results of this study will contribute to a better understanding of the risk factors of infection with HIV and thus allow for better targeting of group-specific interventions, particularly for CSWs and their clients. Further investigation of a possible association between injectable contraceptive use and HIV infection is needed.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID