摘要:

Objective:Cytomegalovirus (CMV) is a frequent opportunistic viral pathogen in patients with AIDS leading to retinitis and other serious manifestations. CMV disease may be successfully treated. Prophylactic antiviral therapy has been shown to reduce the risk of CMV disease if initiated early. We evaluated PCR and the antigenemia test as methods for early detection of CMV disease.Methods:Two-hundred HIV-seropositive subjects with CD4 T-cell counts below 100 × 106/l were monitored with CMV polymerase chain reaction (PCR), the antigenemia test, blood cultures and CMV immunoglobulin (Ig) G and IgM titres every second month for 1 year.Results:Thirty-eight patients (19%) developed CMV disease. The PCR test detected CMV DNA a median of 46 days before onset of disease. This was earlier than the median of 34 days for the antigenemia test and a median of 1 day for CMV blood cultures. Univariate analysis showed that the CMV PCR, the antigenemia test and blood cultures all had significant predictive values for subsequent development of CMV disease with odds ratios (OR) of 30, 22 and 20. CMV serology had no predictive value. Multivariate analysis showed that the PCR method was superior to the other tests; OR: CMV PCR 10.0, antigenemia test 4.4 and CMV cultures 4.3. No clinical parameters had any significant predictive value in the stepwise multivariate model.Conclusions:The CMV PCR and the CMV antigenemia tests are both sensitive methods that may predict development of CMV disease up to several months prior to clinical disease. These methods make it possible to select patients at high risk for CMV disease and suitable for prophylactic therapy against CMV.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background:Evidence from ecological studies and from studies of and sexually transmitted disease (STD) patients in sub-Saharan Africa suggests that there is a protective effect of male circumcision against HIV infection. There are, however, few population-based studies that have controlled adequately for potential confounding factors.Methods:Data from five population-based studies in north-western Tanzania were used to investigate the association between male circumcision and the risk of HIV infection and STD. The effects of circumcision on HIV prevalence, syphilis (positiveTreponema pallidumhaemagglutination; TPHA) and self-reported STD were analysed, controlling for a range of demographic and sociocultural variables, and indicators of sexual behaviour.Results:In north-western Tanzania, circumcision was previously restricted to Muslims and specific ethnic groups, but is now more widespread, particularly in urban areas and among more educated men. Assessment of the reliability and validity of self-reported circumcision status showed that these data could be considered fairly accurate, although there was some tendency for circumcision to be over-reported. On univariate analysis, circumcision status was unrelated to HIV prevalence in most studies. After controlling for confounding variables, however, there was a modest but significant reduction of the HIV prevalence among circumcised men [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.48–0.81]. This effect appeared stronger in urban areas (OR, 0.46; 95% CI, 0.32–0.68) and roadside villages (OR, 0.65; 95% CI, 0.42–1.01) than in rural areas and islands (OR, 1.00 and 1.01 respectively). There was no association between circumcision status and syphilis serology (TPHA), but there was a positive association between circumcision and self-reported STD, although this was not significant after adjustment for confounding variables.Conclusion:Male circumcision has a protective effect against HIV infection in this population, which may be stronger in urban areas and roadside settlements than in the rural areas. Ethnic group and religious denomination are no longer the sole determinants of male circumcision.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objectives:To evaluate the effect of sequence variation within the gp120 V3 loop on CD4 T-cell recognition.Design:CD4 T-cell clones were generated using synthetic peptides to circumvent the difficulties of using polyclonal T-cell responses. Peptides based on other HIV isolates were then used to determine the influence of single and multiple sequence differences.Results:Three of the panels of T-lymphocyte clones (TLC), which were all specific to diverse HIV-1 clade B gp120 V3-loop peptides differing in a limited number of residues, had heterogeneous patterns of response to peptides differing in length and sequence indicating that they recognized distinct but overlapping epitopes. The panels of TLC also differed in the extent to which they tolerated sequence differences between cell-culture-adapted or primary HIV-1 isolates. One panel responded to peptides based on several clade B and one clade D isolate. In contrast, two panels, generated from two different donors using the same peptide, only responded to a limited number of clade B isolates, whereas another only recognized HIV-1BRU. Two of the panels were also stimulated by peptides based on clinical isolates from one patient with some sequence changes enhancing T-cell recognition.Conclusions:These data are consistent with highly diverse CD4 T-cell recognition of the HIV-1 gp120 V3 loop, which is influenced by the sequence differences within the T-cell epitopic region and has implications for the pathogenesis and design of vaccines against HIV-1.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To determine whether proton magnetic resonance spectroscopy (MRS) demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected individuals.Design:Both prospective and retrospective cross-sectional analyses of MRS in asymptomatic HIV-infected individuals.Setting:Two specialist HIV/AIDS outpatient facilities in London.Participants:Eighty-four HIV-1-seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high-risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV infection as controls.Main outcome measures:Single voxel, gradient-localized proton MRS performed at 1.5 T with a 135 msec echo-time and 1600 msec repeat-time in an 8 ml volume of interest positioned in the parieto-occipital white matter. Spectroscopic results were expressed as ratios between the areas under the N-acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks.Results:There were no differences between those controls at high and those at low-risk for HIV infection. Comparing the combined control groups with the asymptomatic seropositive patients there were statistically significant differences in NA/Cho, NA/Cr (both P< 0.05) and NA/(NA + Cho + Cr) (P< 0.01).Conclusion:Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during asymptomatic HIV-1 infection.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:The HIV Tat protein is a transcriptional transactivator of the HIV-1 long terminal repeat (LTR) promoter element. Its activity depends on its direct interaction with the trans-activation response (TAR) element, although TAR-independent activation by Tat has been demonstrated in different cells. Herpesviruses in general and human cytomegalovirus (HCMV) in particular are often isolated from HIV-1-infected patients and could play a role in the activation of latent HIV and in a subsequent increase in HIV replication. HCMV immediate early gene products (IE1 and IE2) are nuclear phosphoproteins that play a pivotal role in HCMV replication and have been shown to transregulate both viral and cellular gene expression. It has repeatedly been shown that HCMV IE1/IE2 can independently transactivate HIV-1 LTR. The aim of this study was to investigate IE1/IE2 transactivation of HIV-1 LTR in a CD4+ T-cell line in the absence and presence of HIV-1 Tat to establish whether IE1/IE2 can synergize with Tat.Methods:HIV-1 LTR transactivation by HCMV IE1/IE2 in the presence and absence of HIV-1 Tat was determined by transient transfection experiments of J-Jhan lymphoblastoid cells with a series of different expression vectors.Results:We found a strong synergistic transactivaton between HIV Tat and the IE1–IE2 complex on HIV LTR activity using vectors driven either by wild-type LTR or by the nuclear factor NF-κB response element-mutated HIV LTR. IE1/IE2 synergism with HIV Tat was also observed in Sp1 binding site-mutated or TAR-deleted LTR, which cannot be activated by Tat alone. This cooperation is abolished when the region in IE2 that binds the TATA box binding protein is deleted.Conclusions:The results obtained indicate that Sp1-binding and TAR sequences are not strictly required for Tat responsiveness when Tat is directed to the HIV promoter by HCMV IE1–IE2. This synergistic effect is mediated by the IE2 and TATA-binding region, and could play a major role in HIV activation when cells are infected by both viruses, a feature often observed in AIDS patients.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:Recently, it has been shown that a homozygous 32 base-pair deletion in the gene encoding CKR-5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1. We have investigated whether HIV-seropositive individuals who were heterozygous for the CKR-5 deletion had a different course of the disease.Design:Thirty-five high-risk HIV-seronegative and 99 HIV-seropositive Danish homosexual men followed from 1985 to 1996 and 37 blood donors were analysed for their CKR-5 genotype by polymerase chain reaction.Results:Two (6%) of the 35 HIV-seronegative subjects at high-risk of infection were homozygous and seven (20%) were heterozygous for the CKR-5 deletion. This was not significantly different from the distribution in normal donors. Twenty-two (22%) of the 99 HIV-seropositive subjects were heterozygous and none was homozygous. Two subgroups of patients who had an opposite course of the HIV disease were identified. Of nine long-term non-progressors, six (66%) were heterozygous for the deletion. This frequency is significantly higher than in nine rapid progressors of whom none was heterozygous. The frequency of heterozygotes in long-term nonprogressors was also significantly higher than in the cohort as a whole. A Kaplan-Meier plot of the HIV-seropositive subjects, of whom 57 developed AIDS, showed a significantly better prognosis within the first 7 years of follow-up for those who were heterozygous for the deletion. Heterozygous individuals also had a significantly slower decrease in CD4 T-cell count per year.Conclusion:Individuals who are heterozygous for the 32-base-pair deletion in the CKR-5 gene have a slower decrease in their CD4 T-cell count and a longer AIDS-free survival than individuals with the wild-type gene for up to 11 years of follow-up.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To compare the efficacy of two- and three-drug regimens for treating Mycobacterium aviumcomplex (MAC) bacteremia in patients with AIDS.Design:Randomized open-label clinical trial.Setting:Outpatient HIV specialty centers' clinics.Patients:A total of 106 adults with AIDS and MAC bacteremia.Interventions:Patients were treated with clarithromycin 500 mg twice daily and ethambutol 800–1000 mg daily and were randomized to receive clofazimine 100 mg daily or no clofazimine.Main outcome measures:Quantitative blood MAC cultures, symptoms, adverse reactions and survival.Results:Patients randomly assigned to three drugs had significantly higher baseline colony counts of MAC in blood than patients receiving two drugs. The proportion of patients becoming culture-negative was 65% in the two-drug group and 54% in the three-drug group. The median time to negative culture was 58 days for patients in the two-drug group and 63 days for the three-drug group. At the last visit during treatment, the mean reduction in colony forming units/ml of MAC in blood was 1.8 log10for the two-drug group and 2.3 log10for the three-drug group. Improvement in fever and night sweats was reported by 87 and 89% of the two-drug patients and 84 and 86% of the three-drug patients. During the study, 38% of two- drug patients and 61% of three-drug patients died (P= 0.032), and time to death was shorter in patients treated with three drugs (P = 0.012). In a multivariate analysis, both assignment to clofazimine and high baseline colony counts of MAC bacteremia were significantly associated with death (P< 0.05).Conclusion:The addition of clofazimine to a regimen of clarithromycin and ethambutol for MAC bacteremia in AIDS patients does not contribute to clinical response and is associated with higher mortality.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To describe the characteristics and outcomes of HIV-infected patients with biopsy-proven cytomegalovirus (CMV) pneumonia.Design:Retrospective study.Setting:A 900-bed acute care facility in New York City.Patients:Eighteen HIV-infected patients with pathologically confirmed CMV inclusions in lung tissue without other pathogens and 36 control patients with biopsy-provenPneumocystis cariniipneumonia (PCP) selected for comparisons by computer-generated random sequential numbers.Main outcome measures:Demographic, clinical, laboratory, radiological findings, and in-hospital mortality.Results:Eighteen HIV-infected patients were found to have CMV lung infection alone. Pathologic findings were pneumonitis (n = 11); pneumonitis and pulmonary vasculitis (n = 1); and CMV inclusions alone (n = 6). All presented with respiratory symptoms (cough or dyspnea), 89% had fever, 83% had radiological abnormalities, and 56% had severe hypoxemia. The pulmonary presentation was similar except for higher lactate dehydrogenase (median, 449 versus 329 IU/l;P= 0.03) and presence of pleural effusions (33 versus 0%;P= 0.001) in CMV patients. Multivariate analysis showed that CD4 counts ≤ 12 × 106/l (odds ratio, 9.2;P= 0.029) and extrapulmonary CMV (odds ratio, 20.4;P= 0.039) were independently associated with CMV pneumonia. Seventeen patients received specific anti-CMV therapy for a mean of 22 ± 13 days. In-hospital mortality was higher in patients with CMV pneumonia (odds ratio, 11.9;P= 0.002). The median time from admission to death was 31 days.Conclusions:CMV lung infection was seen in severely immunosuppressed HIV-positive patients and was associated with clinical pneumonitis with high early mortality. Although the clinical features resemble PCP, the presence of extrapulmonary CMV disease should suggest the diagnosis of CMV pneumonia.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To determine whether vitamin A deficiency is associated with maternal-infant HIV transmission among HIV-infected pregnant women in two United States cities.Methods:Third trimester serum vitamin A levels were evaluated using high-performance liquid chromatography in 133 HIV-infected women who delivered livebirths during May 1986 to May 1994 and whose infants had known HIV infection status.Results:Sixteen per cent (seven out of 44) of the transmitting mothers and 6% (five out of 89) of the non-transmitting mothers had severe vitamin A deficiency (<0.70 μmol/l; P = 0.05). Maternal-infant transmission was also associated with prematurity <37 weeks gestation (P = 0.02), and Cesarean section delivery (P = 0.04), CD4 percentage (P = 0.03) and marginally associated with duration of membrane rupture of ≥ 4 h (P = 0.06) by univariate analysis. In a multivariate logistic regression model, severe vitamin A deficiency [adjusted odds ratio (AOR), 5.05; 95% confidence interval (CI), 1.20–21.24], Cesarean section delivery (AOR, 3.75; 95% CI, 1.10–12.87), and prematurity (AOR, 2.25; 95% CI, 1.22–4.13) were associated with transmission after adjusting for CD4+ percentage, and duration of membrane rupture.Conclusion:Increased risk of maternal-infant transmission was associated with severe vitamin A deficiency among non-breastfeeding women in these cohorts from the United States.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID