ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective.HIV-1 and HIV-2 isolates representing various geographic regions and distinct viral subtypes were examined for their ability to establish bothin vitroandin vivoproductive infections ofMacaca nemestrina(pigtail macaque) peripheral blood mononuclear cells.Methods.Animals were inoculated with either autologous cell-associated or cell-free viral preparations of selected isolates. HIV-specific immune responsiveness, hematologic changes, genetic variation, and virus burden were monitored as delineators of HIV pathogenesis.Results.HIV-2 replicationin vitroandin vivocorrelated with nascent antigen production and rising viral titers as determined by infectious center assays. Infection was detectable by polymerase chain reaction amplification of proviral sequences in macaque cells as early as 1 week postinoculation. Two distinct patterns of CD4+ cell depletion induced by HIV-2 infection were observed during the first month postinoculation and characterized by a moderate loss sustained through 20 weeks postinoculation or a substantial loss maintained long-term (> 90 weeks). Identity between inoculating viral stocks and subsequent viral isolates from animals was established comparatively by limited sequence analysis of specific domains within the HIV-2polandenvgenes. In contrast, replication of HIV-1 isolates was limited or only semipermissivein vitro.Intravenous inoculation of HIV-1 field isolates, using conditions successful for HIV-2 (for example, identical viral titers), failed to establish a productive viral infection leading to seroconversion or fluctuations in hematologic cell markers. Infection with a high-titer inoculum of a laboratory-adapted HIV-1 strainin vivo, as demonstrated by polymerase chain reaction analysis, produced seroconversion in the absence of overt viral replication or hematologic variations in one out of four animals.Conclusions.This system provides for multifaceted modeling of HIV pathogenesis, primarily with HIV-2 and potentially with HIV-1/-2 chimerics, in support of immunotherapeutic developments and critical evaluation of intervention practices.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective.To investigate the diagnostic value of cerebrospinal fluid (CSF) culture for opportunistic viruses from HIV-1-infected individuals.Methods.A 4-year prospective study was conducted using a participant population consisting of 186 HIV-1-infected individuals without neurologic disease, 73 HIV-1-infected individuals with encephalopathy, myelopathy, and/or peripheral neuropathy, and 10 controls. CSF samples recovered at 1-year intervals were subjected to virus culture using techniques commonly used in the clinical laboratory setting.Results.CSF samples obtained from only 15 of the 269 (5.6%) participants yielded an opportunistic virus upon culture. Cytomegalovirus, herpes simplex virus types 1 and 2, adenovirus, and presumptive enteroviruses were identified. No consistent correlation was observed between the detection of an opportunistic virus within a CSF sample and the presence or future development of neurologic disease. However, a significant correlation was observed between culture of virus from CSF and the future development of abnormal CD4+ (X2,P= 0.0286) and CD8+ (X2,P= 0.0018) lymphocyte counts in HIV-1-infected participants without neurologic disease.Conclusion.These results show that culture of CSF to screen for opportunistic viruses is neither diagnostic nor predictive of neurologic disease in HIV-1-infected individuals. Nevertheless, the presence of virus within CSF may be an indicator of HIV-1-mediated immune dysfunction and a predictor for future development of abnormal CD4+ and/or CD8+ lymphocyte counts.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective:To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS.Design.Randomized, double-blind placebo-controlled trial.Setting.Multicentre study in five European countries and Australia.Patients.Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 106/l, or if > 400 x 106/l, subjects with HIV p24 antigenaemia (> 10pg/ml).Intervention.Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250mg four times daily dose regimen for the first 4 weeks.Main outcome measures.The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed.Results.Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rankp=0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P=0.01); a trend in a delay in progression to CDC stage IV disease was observed (P=0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P=0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed.Conclusions.Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective.To investigate the roles of mutation, competition and population dynamics in the emergence of drug resistant mutants during zidovudine therapy.Design.A mathematical model of the population dynamics of the viral quasispecies during zidovudine therapy was investigated.Methods.The model was used to simulate changes in the numbers of uninfected and infected cells and the composition of the viral quasispecies in the years following initiation of therapy. Resulting scenarios in asymptomatic and AIDS patients were compared. The model was also used to investigate the efficacy of a treatment regimen involving alternating zidovudine and dideoxyinosine therapy.Results.The behaviour of the model can be divided into three stages. Before therapy, mutation maintains a small pool of resistant mutants, outcompeted to very low levels by sensitive strains. When therapy begins there is a dramatic fall in the total viral load and resistant strains suddenly have the competitive advantage. Thus, it is resistant strains that infect the rising number of uninfected CD4+ cells. During this second stage the rapid effects of population dynamics swamp any effects of mutation between strains. When the populations of infected and uninfected cells approach their treatment equilibrium levels, mutation again becomes important in the slow generation of highly resistant strains.Conclusions.The short-term reduction in viral replication at the initiation of therapy generates a pool of uninfected cells which cause the eventual increase in viral burden. This increase is associated with (but not caused by) a rise in frequency of resistant strains which are at a competitive advantage in the presence of the drug. When therapy is ceased, reversion of resistance is slow as resistant strains are nearly as fit as sensitive strains in the absence of drug.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective.Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) is more common in patients with HIV infection. In non-infected patients, TMP-SMX hypersensitivity is more common in those with a slow acetylator phenotype. This study was conducted to determine whether the slow acetylation phenotype is associated with an increased risk of hypersensitivity to TMP-SMX in patients with HIV infection.Methods.Acetylation phenotype was determined in 28 HIV-infected subjects, of whom 16 had prior TMP-SMX hypersensitivity and 12 had received long-term TMP-SMX therapy without hypersensitivity, as well as in 29 healthy controls. Acetylation phenotype was determined by measuring the ratio of two urinary caffeine metabolites, 5-acetylamino-6-amino-3-methyl uracil (AAMU) and 1-methylxanthine (1 -MX), after ingestion of a single 200 mg dose of caffeine.Results.Of the 28 HIV-infected subjects, 20 (71%) expressed a slow acetylation phenotype and eight (29%) a fast phenotype. By comparison, of the 29 healthy controls, 15 (52%) expressed a slow phenotype (P= 0.11). Of the 16 HIV-infected subjects with prior TMP-SMX hypersensitivity, 15 (94%) had a slow acetylation phenotype, whereas only five out of 12 (42%) non-hypersensitive subjects had a slow acetylation phenotype (P>0.01).Conclusions.A slow acetylation phenotype is a risk factor for hypersensitivity to TMP-SMX in HIV-infected subjects.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objective.To evaluate the effects of continued drug use and other cofactors on progression to AIDS among HIV-infected injecting drug users.Design.A prospective study.Setting.The Muirhouse Medical Croup in Edinburgh, Scotland, UK.Subjects.A total of 156 HIV-infected injecting drug users.Main outcome measures.Progression to AIDS and low absolute CD4 counts.Results.Of this group, 48% will have progressed to AIDS 10 years after seroconversion. Age and low absolute T4 counts had a significant effect on progression to AIDS, with older patients progressing more rapidly. Sex had no significant effects on progression. Absolute CD4+ counts and the CD4:CD8 ratio were significant predictors of progression among the group. Concurrent heroin injecting increased the risk of progression to AIDS. No significant effects were observed for use of other drugs.Conclusions.Our findings suggest that continued drug use may have an accelerating effect on progression to AIDS. Age also had an accelerating effect on progression, but sex had no significant effects. In general, the study group did not appear to progress at a different rate from other similar groups of HIV-infected individuals, despite the fact that this was a relatively young cohort. These data were based on accurate estimates of seroconversion dates.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objectives.To estimate the excess mortality of injecting drug users (IDU) stratified by HIV serostatus compared with the general population in Italy. To compare total and cause-specific mortality in HIV-positive versus HIV-negative IDU, in order to identify possible HIV-related non-AIDS causes of death in this population.Methods.All IDU attending two drug-treatment centres in Rome who underwent HIV testing between 1985 and 1991 were enrolled into a prospective study. The end-point of the study was death from any cause by 31 December 1991. Mortality rates were compared using age-adjusted standardized mortality ratios and person-time techniques.Results.Of the 2431 IDU, 1661 (68.3%) were HIV-seronegative and 82 seroconverted. Of 181 deaths, comprising 89 from AIDS and 92 from other causes, the mortality rate was 4.5 and 0.8 per 100 person-years in HIV-seropositives and HIV-seronegatives, respectively. For non-AIDS mortality in HIV-seropositives, the overall rate was 1.7 per 100 person-years. Deaths from overdose and endocarditis/embolus tended to be higher in HIV-seropositive than HIV-seronegative IDU, although there was no difference in the rate of deaths due to pneumonia by HIV serostatus.Conclusions.These data are consistent with other studies demonstrating a higher frequency of mortality among HIV-seropositive IDU. The excess in overdose mortality among HIV-seropositives is disturbing and merits further investigation.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objectives.To characterize recent HIV seroconverters in a sexually transmitted disease (STD) clinic population, and examine changing transmission patterns.Methods.We conducted a case-control study nested within a retrospectively defined cohort of individuals attending Baltimore STD clinics between January 1988 and July 1990. Seroconverters, who tested HIV-positive after having a negative test, were compared to both HIV-negative controls, who were also tested twice, and a second, prevalent HIV-positive control group. Controls were matched 2:1 by sex, clinic, and month of HIV test.Results.Forty-nine out of 6175 (0.79%) patients tested at least twice had documented HIV-1 seroconversion. On multivariate analysis, seroconversion was significantly associated with self-reported injecting drug use lodds ratio (OR), 7.3; 95% confidence interval (Cl), 2.3–23)], with being a man who has had sex with other men (OR, 3.5; 95% Cl, 1.2–10), or with having sex with a known HIV-infected person (OR, 11; 95% Cl, 1.3–96). Thirty-five per cent of seroconverters did not report a risk for HIV infection, and a higher proportion of recent seroconverters also reported no risk. Compared to the prevalent positive control group, more seroconverters reported no risk and a lower proportion reported recognized risks. A diagnosis of gonorrhea was also significantly associated with seroconversion (OR, 2.5; 95% Cl, 1.1–5.7).Conclusions.These data suggest increasing heterosexual transmission of HIV in this inner-city STD clinic population. Incident STD, in particular gonorrhea, may increase a patient's risk for HIV infection, suggesting that patients with STD should be targeted aggressively tor HIV prevention activities.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Objectives.To study how condom use in injecting drug users' (IDU) relationships differs according to whether they are HIV-infected, and to whether their sex partner is an IDU.Design and methods.A total of 317 street-recruited IDU were HIV-antibody tested and interviewed about 421 relationships with particular sex partners.Results.Condoms were consistently (100%) used in sex between partners (during the previous 30 days) in 33% of these relationships, and their use was significantly more frequent in relationships of seropositive IDU and in relationships with non-IDU partners. In relationships between seropositive IDU and non-IDU, consistent condom use was reported to be high (68%); this remained unchanged under multivariate controls.Conclusions.Self-reported condom use by IDU in New York, with its relatively mature epidemic, appears to be concentrated where it may most reduce the spread of HIV to non-IDU heterosexuals, i.e., in relationships between infected IDU and non-IDU partners. Differential condom use by serostatus and by partners' drug injection should be incorporated into mathematical models of the HIV epidemic. Causes of the high level of condom use in this subset of relationships may include drug injector altruism and pressure by sex partners; prevention programs should develop ways to use both of these factors to motivate increased condom use.

ISSN:0269-9370    

出版商:OVID    

年代:1994

数据来源: OVID