摘要:

Temperatures > 42°, maintained for >25 min, inactivate >25% of human immunodeficiency virus (HIV). HIV-infected T cells are more sensitive to heat than healthy lymphocytes, and susceptibility increases when the cells are presensitized by exposure to tumor necrosis factor. Thus, induction of a whole-body hyperthermia or hyperthermia specifically limited to tissues having a high viral load is a potential antiviral therapy for acquired immunodeficiency syndrome (AIDS). Accordingly, we incorporated therapeutic hyperthermia into an existing mathematical model that evaluates the interaction between HIV and CD4+T cells. Given the assumptions and limitations of this model, the results indicate that a daily therapy lowering the population of actively infected cells by 40% or infectious virus by 40% would effectively reverse the depletion of T cells. In contrast, a daily decline of 20% of either actively infected cells or infectious virus would have a marginal effect. However, daily reduction by 20% of both actively infected cells and infectious virus could restore T-cell numbers, assuming that permanent damage had not been inflicted on the thymus. Since daily treatments would probably be excessively stressful, whole-body hyperthermia seems unlikely to be clinically useful. In contrast, heating directed specifically to areas of viral concentration may be effective and have a suitable risk/benefit ratio.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The existence of zidovudine (ZDV)-resistant and didanosine (ddl)-resistant human immunodeficiency-1 (HIV-1) variants mutated in the reverse transcriptase (RT) gene has been previously demonstrated. In this study, we tried to follow up the genotypic changes in the RT after the switch of therapy from ZDV to ddl. We studied HIV-1 isolates from 11 patients undergoing ddl therapy. Genotypic data were obtained with differential polymerase chain reaction (PCR) and with direct sequencing after PCR. The prevalence of ZDV resistance-related mutations showed a very slow decrease, particularly when patients had been treated with ZDV for a long time. The appearance of a mutation at codon 74 seemed to be independent of the presence or absence of ZDV resistance-related mutations. The broad genotypic heterogeneity of the isolates and the complexity of the evolution in one patient's isolates plead for large sequencing studies of the RT genome in new therapeutic approaches.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The role of thevpx, vpr, andnefgenes in the replication of simian immunodeficiency virus (SIV) was investigated using point and deletion mutations in these genes. The effects on replication kinetics of single or combined mutants—vpx, vpr, vpx-vpr, vpx-nef, vpr-nef, andvpx-vpr-nef—in established lymphoid CEMx174 and MT-4 cells were negligible, except that the postinfection appearance ofvpx-nef, vpr-nef, andvpx-vpr-nefprogeny virus was slightly delayed in MT-4 cells. Thevpx, but not thevpr, point mutation reverted to wild-type sequences within 12 days after infection, suggesting that stronger selection pressure for Vpx than for Vpr expression might exist in these established cell lines. In contrast to growth in the lymphoid cell lines, replication ofvpx-deleted viruses in macaque peripheral blood mononuclear cells (PBMC) was severely impaired, indicating that Vpx is necessary for efficient replication in PBMC. In contrast, thevprmutant exhibited different degrees of impairment depending on the donor animal used as a source of PBMC. A virus encoding a Vpx-Vpr fusion protein replicated in PBMC comparably to avprdeletion mutant virus, whereas a frameshift deletion at thevpx-vprjunction of this mutant eliminated virus replication, suggesting that deletion of the C-terminal half of Vpx was partially compensated by the presence of the large Vpr portion in the fusion protein. Deletion of thenefgene did not affect SIVmacreplication in PBMC. The Vpx and Vpr proteins expressed in COS-1 cells were detected in the extracellular medium and did not crossreact with Vpr- and Vpx-specific antisera, in spite of extensive amino acid similarity between these proteins. These studies indicate the importance of Vpx and Vpr in SIVmacinfection and suggest that these proteins are antigenically and functionally distinct.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

A multicenter placebo-controlled trial of early short-term high-dose methylprednisolone enrolled 78 patients with moderate to severePneumocystis cariniipneumonia (PCP) complicating HIV infection. The mean pressure of oxygen (Po2) at study entry was 55 mm Hg for the 71 patients who had blood gases monitored while breathing room air. Patients were randomized to receive methylprednisolone (40 mg) or placebo parenterally twice daily for 10 days, and the first dose of study medication was given within 24 h of the first dose of antimicrobial therapy for PCP. The primary end point included death, need for mechanical ventilation for >6 days, or a partial Po22

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Fourteen patients previously treated with zidovudine were monitored for laboratory parameters and clinical events during 1 year after introduction of didanosine (ddl) monotherapy. Proviral human immunodeficiency virus type 1 (HIV-1) copy numbers (cell-associated DNA) and concentration of free virions (viremia) were determined using a semiquantitative polymerase chain reaction (PCR). High levels of circulating virus were detected in all patients (range, 17 to 5,934 ± 103/ml of serum). Within 4 weeks of therapy, a decrease of viremia (60 to 98%) was observed in nine patients. After 1 year of treatment, eight of these nine patients still had decreased viremia when proviral HIV DNA was decreased or stable, and CD4+lymphocytes were stable or higher in seven of these eight patients. Antiviral effect was more pronounced in the six patients with CD4+>100/mm3at entry, five of them belonging to the subgroup of the seven responding patients as compared to two of eight patients with CD4+>100/mm3. Clinical events in this small group were not statistically correlated with virologic parameters; however, responding patients had a tendency to stabilize or gain weight. This study suggests that measurement of viremia deserves further study as a marker of antiviral efficacy and might predict, even at 4 weeks, the beneficial potential of ddl.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

To determine how the patterns of inpatient hospital care for HIV-infected patients have evolved in recent years, we analyzed data obtained from a statewide hospital discharge database from Maryland for the years 1988, 1990, and 1992. For each of these years, we compared demography, diagnoses, lengths of stay, use of the intensive care unit, third-party payer, and hospital charges (inflation-adjusted to 1992 dollars). HIV-infected patients accounted for 0.42% of all Maryland's hospital admissions in 1988, 0.68% in 1990, and 1.1% in 1992, with progressively more women and African-Americans hospitalized. Average lengths of stay fell from 11.7 days (1988) to 10.7 days (1990) and 9.5 days (1992) (p < 0.0001). Average charges per admission fell from $11,634 (1988) to $9,938 (1990) and $8,618 (1992) (p < 0.0001). Medicare or Medicaid paid for 50.9% of hospital admissions in 1988, 56.8% in 1990, and 66.8% in 1992 (p < 0.001). In-hospital mortality rates (7.8% in 1988, 7.9% in 1990, and 7.7% in 1992; p = 0.783) were stable, as was severity of illness.P. cariniipneumonia (PCP) was the most common principal diagnosis, but it declined in prevalence from 13.6% in 1988 to 9.1% in 1992 (p < 0.0001). Principal diagnoses of other opportunistic infections remained stable (8.0% in 1988, 9.9% in 1990, 8.6% in 1992; p = 0.90), as did other nonopportunistic infections (32.8% in 1988, 27.2% in 1990, and 30.0% in 1992; p = 0.16). Non-PCP pneumonias increased from 7.6% (1988) to 10.2% (1992) (p < 0.0001). Substance abuse as a principal or secondary diagnosis increased from 30.9% (1988) to 34.3% (1992) (p < 0.001). HIV-infected patients comprised an increasing percentage of statewide hospital admissions from 1988 to 1992, with African-Americans, women, and substance abusers having increasing rates of admission. Although severity of illness and mortality rates remained unchanged, lengths of stay and hospital charges have declined, partly offsetting economic consequences of the higher incidence of hospital use.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Previous studies have found lower mortality rates for AIDS-relatedPneumocystis cariniipneumonia (PCP) in hospitals with higher levels of experience with PCP. It is not known if patients are selectively referred to better hospitals or if there is a learning curve whereby outcomes improve as physicians gain experience in treating PCP. We assessed cases of PCP at 140 Veterans Administration (VA) Medical Centers in the United States. During 1987–1991, 3,981 patients were hospitalized with first-episode AIDS-related PCP. Mortality at 30 days after admission. For these 3,981 hospitalizations at the 140 study hospitals, the 30-day mortality was 19%. Logistic regression models indicate that older age, race, geographic area, earlier year of treatment, hospitalization in the previous 12 months, and lower levels of hospital experience with AIDS were significant predictors of mortality at 30 days after admission. Compared with hospitals that had treated three cases or fewer of first-episode PCP, the odds of mortality at 30 days at hospitals that treated >50 cases of first-episode PCP were 0.73 (95% confidence interval 0.58–0.91), after controlling for differences in characteristics of the patients, year, and region. Mortality of patients with AIDS-related PCP decreases as VA hospitals gain experience. Longitudinal analyses over a 5-year period suggest that a learning curve best explains this finding.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We recently reported clonal human immunodeficiency virus (HIV) involvement in four acquired immune deficiency syndrome (AIDS)-associated non-B-cell lymphoproliferations. In three of these cases HIV expression was localized to tumor-associated macrophages. Because one of the cases had a major component involved in angioproliferation, we speculated that some form of Kaposi's sarcoma (KS), which also has a major component of angioproliferation, might be involved clonally with HIV. The current study is an evaluation of four cases of KS and control tissues taken from four patients who died with complications of HIV disease. With use of the inverse polymerase chain reaction technique to identify clonal forms of HIV, a clonal form of HIV was found in one of four KS cases. The HIV-positive tumor was an early KS lesion of the bowel, and uninvolved bowel from the same patient showed no clonal HIV. Immunohistochemical analysis demonstrated the presence of prominent HIV-expressing macrophages that also coexpressed high levels of HIVtat, basic fibroblast growth factor, and interleukin-6. These data provide evidence for a pathogenic process termed “sequential neoplasia,” wherein a clonal macrophage provides a growth factor milieu stimulating the proliferation of a responder cell population that ultimately becomes autonomous. In the current case, the macrophages expressing HIV were located adjacent to the KS tumor tissue and were found to be producing known KS growth factors. The absence of finding clonal HIV in three more advanced KS lesions suggests that the clonal macrophage may be required only for early pathogenesis and that sequential neoplastic changes occurring in the endothelial cells gave rise to autonomous KS. This “hit and run” role for HIV as a KS infectious agent may help explain some of the confusing epidemiologic findings concerning the pathogenesis of KS.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The objectives of this study were (a) to compare the CD4+lymphocyte profiles over time of two groups of patients hospitalized for tuberculosis (TB) treatment [a group of patients with TB only (TB group) and a group dually infected by HIV and TB (HIV/TB group)] and (b) to assess the usefulness of the total lymphocyte count (TLC) as a surrogate of the CD4+lymphocyte count in the HIV/TB group. A total of 345 patients were enrolled in the study of whom 104 (29.8%) were HIV seropositive (HIV/TB). On admission, the CD4+lymphocyte counts of the HIV/TB cohort were significantly lower than the TB group with medians of 230 (interquartile range, 90–475) and 630 (500–865), respectively (p+lymphocyte count increased significantly in both cohorts on routine TB treatment. A TLC of 1,300–1,500 cells/mm3was found to be predictive of a CD4+lymphocyte count of <200 cells/mm3both on admission and after 1 month of TB therapy. We conclude from this study that the positive influence of TB therapy on the CD4+lymphocyte count strongly suggests an additional avenue of influence on the course of HIV infection, whereas the usefulness of the TLC as a surrogate estimation of CD4+lymphocyte count in HIV/TB patients has important implications for the developing world.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID