摘要:

Summary:A novel class of polyanionic proteins with potent anti-human immunodeficiency virus type 1 activity, the negatively charged albumins (NCAs), have been reported previously. In vitro antiviral assays established that these compounds preferentially inhibit virus-cell fusion and syncytium formation and that virus-cell binding is less affected. Here the interaction of the NCAs with synthetic peptides composed of 15-36 amino acids and corresponding to different parts of the gp120 envelope protein is described. Among the gp120 peptides tested, binding of the NCAs was observed only with the so-called V3 loop (amino acids 296-330) and the C-terminal part of gp120. A higher number of negatively charged residues in the albumins resulted in higher binding affinities. NCAs in which, in addition to negative charges, up to 7 or 14 lactose or mannose groups were introduced, respectively, did not exhibit increasing binding affinity. In contrast, mannosylated albumin containing about 14 mannose groups showed an increased binding compared with native albumin. Binding of the NCAs to the V3 and C-terminal oligopeptide was competitively inhibited by sulfated polysaccharide heparin and dextran sulfate. This finding indicates that the binding between the gp120 peptides and the NCAs is likely caused by electrostatic interactions. However, the fact that the dissociation constants of dextran sulfate and heparin are orders of magnitude larger compared with the NCAs indicates that the spatial structure of the proteins and/or hydrophobic interactions between the NCAs and the envelope protein may also be involved.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Recombinant human tumor necrosis factor (TNF) binding protein-1 (r-hTBP-1) and recombinant human soluble dimeric TNF receptor (rhu TNFR:Fc) were used to determine the relative contributions of TNF to phorbol myristate acetate (PMA) and cytokine-induced human immunodeficiency virus type 1 (HIV-1) replication in chronically infected cell lines. Treatment of HIV-1-infected promonocytic U1 cells with r-hTBP-1 or rhu TNFR:Fc reduced PMA-induced HIV-1 p24 antigen production in a concentration-dependent manner, with a maximal inhibition of approximately 90%. Maximal inhibition of p24 antigen production in T-lymphocytic ACH-2 cells was 47% with r-hTBP-1 and 42% with rhu TNFR:Fc. r-hTBP-1 and rhu TNFR:Fc also decreased p24 antigen synthesized by U1 cells in response to other stimuli, including phytohemagglutinin (PHA)-induced supernatant, granulocyte-macrophage colony-stimulating factor, interleukin-6, and TNF. Addition of r-hTBP-1 to U1 cells during the last 4 h of a 24 h incubation with PMA still inhibited p24 antigen production by 15%. U1 cells stimulated with 10-7MPMA released ≈1 ng/ml endogenous TBP-1 with an initial peak observed at 1 h and a second peak at 24 h after PMA stimulation. r-hTBP-1 also partially reversed inhibition of U1 cellular proliferation caused by PMA. Both r-hTBP-1 and rhu TNFR:Fc blocked PMA induction of nuclear factor (NK)-κB DNA-binding activity in U1 cells in association with decreases in HIV-1 replication. We conclude that soluble TNF receptors can inhibit stimuli-induced HIV-1 expression and NF-κB DNA-binding activity in chronically infected U1 cells.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

SummaryHIV-1 primary infection is characterized by a short high titer viremia, which rapidly declines as the immune response emerges. The role of autologous neutralizing antibodies in the decline of viral replication was evaluated in 12 patients with primary or recent HIV-1 infection. Neutralizing antibodies detected for each patient could not generally be observed before several months after isolation of the first obtained HIV isolate. The plasma viral load, as measured by quantitation of the HIV-1 RNA, underwent a global decrease during the first 6 months of the infection, but this decrease did not seem to be associated with the emergence of neutralizing antibodies. The proviral load in peripheral blood mononuclear cells, which was studied by quantitative DNA polymerase chain reaction, exhibited fluctuations and was not as well curtailed as the plasma viremia in the majority of patients.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:This article describes the features of active tuberculosis in HIV-infected injecting drug users (IDUs) from a low-rate tuberculosis area. The cohort was followed in a hospital-based HIV/AIDS registry, and data were extracted from the registry, patient charts, and the Tuberculosis Control Program of the Connecticut Health Department. The setting was an acute care inner-city hospital-based health care system, with a high incidence of AIDS, serving a small-to-medium urban area in Connecticut. The patients were 905 HIV-infected IDUs whose time of HIV diagnosis (TOHD) was between 1984 and 1992. The outcome measures were demographics, clinical characteristics, and morbidity rates of active tuberculosis. Of the 27 IDUs who developed active tuberculosis, none were white, all but one were male, and only one was known to have had a positive purified protein derivative (PPD) reaction prior to TOHD: 59% of cases developed in patients known to be HIV infected, 11% occurred in established AIDS patients, and 67% qualified as extrapulmonary tuberculosis (that is, AIDS defining by pre-1993 definitions). In 22% of cases, bothMycobacterium tuberculosisandM. avium-intracellularewere isolated.Mycobacterium tuberculosiswas most commonly isolated from a respiratory specimen (67%). The annual incidence rate has been ≤1.0% since 1988. The cumulative incidence rate was highest for patients with a positive PPD reaction or a history of tuberculosis (1.4 cases/100 patient years; 52 patients; mean follow-up 4.0 years). The demographics and clinical characteristics of active tuberculosis in our HIV-infected IDUs are similar to those described elsewhere in the United States; the morbidity rates are low and stable. The implications of our findings on tuberculosis control in HIV-infected IDUs may be applicable to health care systems with low tuberculosis rates.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

SummaryTo determine the impact of a food voucher incentive and patient education program on compliance with tuberculin skin test (PPD, purified protein derivative) performance in HIV-infected adults, we analyzed return rates for PPD reading for patients at our urban HIV clinic. The groups studied included patients who received no intervention (controls), patients offered a food voucher incentive, and patients offered a food voucher and patient education intervention. Return rates for PPD reading were 96 (35%) of 272 for the control group, 111 (48%, p = 0.004) of 229 for the food voucher group, and 96 (61%, p < 0.0001) of 158 for the food voucher and patient education group. By univariate analysis, black patients (p = 0.01), males (p = 0.01), older patients (p = 0.004), city residents (p = 0.001), and injection drug users were more likely to return for PPD reading. By logistic regression, food voucher, food voucher plus education, city residence, and male sex were significantly associated with return for PPD reading. Two simple, inexpensive interventions were found to increase compliance with tuberculin skin test performance in HIV-infected adults. Additional interventions are required to achieve better rates of return for PPD reading.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:To determine the prevalence and effect of cytomegalovirus (CMV) co-infection on clinical outcome, the seroepidemiology of CMV was examined in 196 demographically diverse patients with advanced HIV disease. Thirty-six (18.4%) were seronegative for CMV; 31 of these 36 (86.1%) were both non-black and non-homosexual. Invasive CMV disease developed in 41 of 160 (25.6%) seropositive patients and 0 of 36 (0%) seronegative patients (p = 0.00015). Among seropositive patients, the frequency of CMV disease varied markedly according to risk group for acquisition of HIV infection. CMV disease occurred in 26 of 73 (35.6%) homosexual men and 11 of 33 (33.3%) heterosexuals, but only 2 of 47 (4.3%) injection drug users. Sexual exposure as the only risk factor for the acquisition of HIV was a highly significant independent risk factor for invasive CMV when other covariables were considered in a proportional hazards model (risk ratio 5.4, p = 0.0019). The cumulative proportion of all seropositive patients developing CMV disease after 3 years was 31%. CMV serologic status had no effect on occurrence of AIDS-related illnesses other than CMV disease and no effect on survival. Risk for the development of CMV disease varies substantially among different groups of patients with advanced HIV disease and can be assessed using serologic and demographic criteria. The results of this study may be used to influence clinical management and help target prophylactic interventions for CMV disease to high-risk individuals.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:HIV-seropositive patients (n = 67) who had tolerated zidovudine for at least 24 weeks and deteriorated clinically or immunologically within 12 weeks prior to study entry were allocated in an alternating manner to didanosine chewable tablets (400 mg\day) plus zidovudine (500 mg\day) or dideoxicytidine capsules (2.25 mg\day) plus zidovudine (500 mg\day). The combination of didanosine and zidovudine resulted in a more pronounced increase of CD4 cells over time compared to the combination of dideoxicytidine with zidovudine (p < 0.002). The increase of CD4 cells was almost exclusively due to patients with more than 100 CD4 cells/μl. Clinical end points (death, AIDS-defining disease, CDC IV event) were less frequent under didanosine plus zidovudine but failed to reach statistical significance (p = 0.07). For didanosine plus zidovudine the median time on medication during study was shorter (63% vs. 100%, p < 0.05) and the number of patients discontinuing medication prematurely due to side effects was higher (59% vs. 30%, p < 0.02). The present study favors the combination of didanosine and zidovudine in patients deteriorating while receiving zidovudine for >24 weeks in respect to the time course of the CD4 cells. In this small sized study, there seemed to be fewer clinical events in patients on the didanosine combination compared to the combination with dideoxicytidine; however, this trend failed to reach statistical significance and needs therefore to be substantiated by larger studies. However, the lower compliance of the patients may hamper the efficacy of didanosine.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Data from a prospective study undertaken at an urban hospital in Durban, South Africa, were used to investigate associations between maternal-infant HIV transmission, mode of delivery, and specific circumstances of cesarean deliveries. A total of 141 children of HIV-infected women were followed until the children were 15 months of age to determine their HIV status. Supplementary data were collected from obstetric records, masked to the HIV status of the children. In this African and predominantly breast-fed population, infants delivered vaginally were more likely to be infected (39.8% infected) than were infants delivered by cesarean section [22.9% infected; odds ratio (OR), 0.45; 95% confidence interval (CI), 0.20-0.99]. There were no significant differences between cesarean deliveries undertaken following prior rupture of membranes and those undertaken with membranes infact, but numbers for this comparison were small. Singleton cesarean deliveries without concurrent obstetric complications had lower rates of transmission than did vaginal deliveries (OR, 0.20; 95% CI, 0.04-0.94). These results suggest that certain intrapartum events may modify the risk of HIV transmission and highlight the importance of collecting more detailed intrapartum information in order to clarify the route by which mode of delivery may be associated with maternal-infant HIV transmission.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Risk factors for HIV-1 infection among women were assessed through a population-based cross-sectional study in the Arusha region of northern Tanzania. The study participants were obtained by randomly selecting 10-household clusters from Unga limited, the town of Babati, and the roadside village of Matufa, which are urban, semi-urban, and rural communities, respectively. Informed verbal consent for participation in an interview and in HIV-1 testing was sought from each respondent. Blood samples were collected from each consenting individual for HIV-1 antibody testing using enzyme-linked immunosorbent assay (ELISA), and all positive sera were confirmed using repeated ELISA tests. Information of risk factors was obtained through the interview process using a structured questionnaire. Of the 567 women who gave blood samples, 48 (8.5%) were HIV-1 positive. The HIV-1 seroprevalence rates among women in the urban area, the semi-urban area, and the rural village were 14.4%, 6.9%, and 2.3%, respectively. Factors associated with significantly higher HIV-1 seroprevalence were urban residence; history of having traveled out of the Arusha region within Tanzania, as well as having traveled abroad; having multiple sexual partners; and having sexual intercourse under the influence of alcohol. Women who reported ever having used condoms had significantly higher probability of being infected with HIV-1 than those who had never used condoms, suggesting that condom use may be a marker of high-risk sexual behaviour and that condom use is probably not adhered to in a way that consistently protects against HIV-1 infection. These results suggest the need for health education interventions aimed at increasing appropriate and consistent condom use and reduction of the number of sexual partners.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Geographic and demographic correlates of risk for HIV-1 seropositivity were studied in 120,216 young men selected by lottery for service in the Royal Thai Army (RTA). The study population consisted of men selected between November 1991 and May 1993. Venous blood was collected at induction, and a brief demographic questionnaire was administered. HIV-1 seropositivity was established by Western blot confirmation of duplicate reactive ELISAs. Geographic variables provided the strongest correlate of risk, clearly distinguishing residents of the upper north, Bangkok, and the central region from the northeast. Overall 12.2% of men from the upper north were HIV-positive. Men who had lived in rural areas were at less risk in most regions of the country, but had equal risk in the upper north. Unmarried men and those with less education were at higher risk throughout the country. These data provide valuable information on the prevalence of HIV infection in one segment of the general population. Continued surveillance of this group will facilitate evaluation of Thailand's response to the epidemic.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID