Journal of acquired immune deficiency syndromes最新文献

A high percentage of HIV-1-infected infants and children in Romania are coinfected with hepatitis B virus. Little information is available on the impact of concurrent hepatitis B infection on the course of HIV-1 infection. We conducted a prospective cohort study over 1 year in a group of 68 HIV-1-infected infants and children to determine whether hepatitis B surface antigenemia, neopterin, and beta 2-microglobulin (B2M) predicted death. Among the 44 hepatitis B surface antigen-positive (HBsAg+) subjects at enrollment, 13 (30%) died during 1 year of follow-up. In comparison, two of 24 (8%) HBsAg-negative subjects died (RR = 7.7; p = 0.05). Higher initial serum concentrations of neopterin and B2M were negatively associated with survival. After stratifying by baseline clinical evidence of HIV-related disease, survival was negatively associated with HBsAg+ status (p = 0.04) in 33 children in stage P-2, adjusting for age, serum neopterin, and serum B2M levels. The results of this study suggest that serum neopterin is a marker for severity of clinical illness and that HBsAg+ status increases the mortality rate among children with clinical evidence of HIV infection.

Surrogate markers generally used for observation of patients infected with human immunodeficiency virus (HIV) and their plasma and cellular viral load were assayed in a series of 40 patients before initiation of zidovudine therapy. Plasma viremia was positive in 62.5% of patients and was statistically correlated with clinical stage, CD4+ T cell count, CD8+ T cell count, beta 2-microglobulin level, neopterin level, and immunoglobulin A level. Cellular viremia was positive in 95% of patients and was correlated with clinical stage, CD4+ T cell count, beta 2-microglobulin, neopterin levels, and disease progression during the following months. A discordance was found between p24 antigenemia, even after acid dissociation of immune complexes, and plasma viremia. In fact, p24 antigenemia was correlated with only biological markers of immune activation as beta 2-microglobulin and neopterin levels. The measurement of anti-p24 antibodies did not appear discriminative in our staging. Plasma viremia, like CD4+ T cell count, reflects the patient's status at the time of assessment. Cellular viremia could be more informative for the prediction of future clinical progression.

Data on the prevalence and patterns of use of concomitant medications among participants in three large phase III clinical trials of zidovudine (ZDV) in human immunodeficiency virus type 1 (HIV-1) infection were analyzed. Overall, 2,801 patients reported 43,331 uses of concomitant medications. Over 85% of clinical trial participants used one or more concomitant medications at some point during the study. Patients with acquired immune deficiency syndrome (AIDS) used an average of 7.1 drugs per month. Patients with AIDS-related complex (ARC) or who were asymptomatic used relatively fewer drugs: 3.1 and 2.7 per month, respectively. Fourteen percent of patients with AIDS used more than 10 concomitant medications per month. The three most commonly utilized classes of drugs were antiinfectives (57%), analgesics or antipyretics (55%), and vitamins (47%). A total of 17% of patients overall and 30% of AIDS patients used acyclovir while on trial. Consumption of prescription drugs was greater, and "over-the-counter" drugs less, among AIDS patients. Reported use of agents not approved by the Food and Drug Administration or approved drugs used for off-label indications was infrequent. Overall use of concomitant medications did not differ across demographic subgroups when corrected for disease stage at the time of enrollment. White, non-Hispanic, homosexual and bisexual men consumed significantly more antivirals and vitamins than other trial participants. Women in all three protocols took more analgesics or antipyretics than did men.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the completeness of human immunodeficiency virus (HIV) reporting among hospital inpatients whose records listed diagnostic codes for HIV infection but who did not meet the 1987 AIDS case definition, we conducted a statewide hospital study of admissions between January 1, 1986 and December 31, 1990. Of the 396 HIV-infected hospital inpatients identified, 313 (79%) had been reported to the State HIV Registry. HIV reporting was less complete for patients who were older and/or were blood product recipients. Of the 313 reported patients, 189 (60%) had been reported prior to their first hospital admission. Temporal improvements were noted in the completeness of HIV reporting among the hospital patients (1986: 65%; 1987: 81%; 1988: 64%; 1989: 82%; 1990: 86%; Chi square for linear trend 9.6, p < 0.01) and prior to their first hospital admission (1986: 31%; 1987: 34%; 1988: 49%; 1989: 64%; 1990: 72%; Chi square for linear trend 26.6; p < 0.01). Women were more likely than men to be reported prior rather than during or after their first hospital admission (71% vs. 55%; p < 0.01). Of the 155 patients with CD4+ T-lymphocyte test results, 41 had CD4+ counts < 200 mm3 and met the 1993 but not the 1987 AIDS case definition. In South Carolina most (79%) diagnosed, hospitalized, HIV-infected patients had been reported to the State HIV REgistry, with improvements in reporting occurring over time. Findings suggest that the 1993 AIDS case definition will improve our ability to monitor severe morbidity related to HIV.

Specific pathogen-free cats were experimentally infected with feline immunodeficiency virus (FIV) and subsequently exposed to common infectious pathogens and immune stimuli over a 3-year period. Cats with preexisting FIV infection showed signs of disease after exposure to Haemobartonella felis, Toxoplasma gondii, feline herpesvirus-1, and feline calicivirus similar to signs in non-FIV-infected cats, although they were more severe. No adverse effects of immunization with inactivated rabies virus vaccine and a synthetic polyproline immunogen were observed in either FIV-infected or non-FIV-infected cats, whereas the application of a diphtheria-tetanus-pertussis vaccine caused transient fever and lymphadenopathy in both groups of animals. Primary immune responses to pathogens or immunogens were usually delayed or diminished in FIV-infected compared with non-FIV-infected cats. Repeated infections and immune activation had no significant effects on the levels of FIV-specific antibodies or on the proportion of peripheral blood mononuclear cells (PBMCs) containing FIV proviral DNA. However, FIV-infected cats that were not exposed to immune stimuli had lower CD4+ T-lymphocyte numbers and lower CD4+/CD8+ T lymphocyte ratios at the end of the 3-year study than FIV-infected cats exposed to cofactors. The latter also had normal levels of interleukin-3 receptor (IL-2R) and major histocompatibility class II (MHC-II) antigen expression on PBMCs, while FIV-infected cats not exposed to cofactors had up-regulated IL-2R and down-regulated MHC-II antigen expression. It was concluded that repeated immune stimulation did not have a deleterious effect on the course of FIV-induced immunodeficiency.

As more women of childbearing age are being identified as HIV infected, vertical transmission to the fetus and/or neonate is an increasingly significant therapeutic problem. Currently the use of zidovudine is one of the few specific measures available, and as a potentially teratogenic and fetotoxic agent, any decision for its use requires evaluation of the potential for fetal damage. In a series of 104 cases of intentional or inadvertent use of zidovudine at differing gestations in pregnancy, there were eight spontaneous first trimester abortions, eight therapeutic terminations, and eight cases of fetal abnormality occurring among a total of 88 cases where the pregnancy progressed. Analysis and correlation of antenatal data and drug therapy with individual cases failed to show any specific abnormality that could reasonably be attributed to zidovudine therapy. While not proving safety, these data add to previous smaller series with similar findings, thus lending tenuous support to the use of this agent. Continuing studies are required, particularly to clarify the possibility of long-term developmental defects.

Previous studies have suggested that salivary secretions may act as inhibitors of HIV-1 replication in vitro. This inhibitory activity was determined to be associated mainly with secretions obtained from the human submandibular-sublingual glands, and subsequent electron micrographs revealed the association of viral particles with the salivary sediment. Fractionation of human submandibular-sublingual (HSMSL) saliva by size-exclusion chromatography was initiated, and resulting fractions were tested for their ability to modulate the replication of HIV-1 using a plaque assay on HeLa CD4+ cell monolayers. Results indicated that the filtration-sensitive inhibitory activity was primarily associated with the mucin-rich fractions, and the inhibitory activity was found to reduce the number of infectious units by 75%. To determine the identity of the salivary components involved, adsorption experiments involving the interaction of HIV particles with immobilized salivary components were performed. Immunological counter staining revealed an interaction of HIV particles as well as recombinant gp120 with the lower-molecular-weight mucin. Electron microscopic examination of the mucin-rich fractions-HIV incubates revealed the aggregation of virus particles by salivary components. These results suggest that human salivary mucins may have a role in modulating the infectivity of HIV-1.

The purpose of this cross-sectional investigation was to address for the first time at what stage(s) the human immunodeficiency virus (HIV) has an influence on resting energy expenditure (REE). The subjects were 53 gay male volunteers who were grouped according to HIV status and symptoms. REE was measured by indirect calorimetry. REE was significantly different between WR 0 (1.11 kcal/min) and WR 3/4 (1.45 kcal/min) (p < 0.05). The indication of a change in REE in the midstages of HIV infection lends support for early intervention of nutritional support.

Much confusion exists about federal regulations governing the enrollment of prisoners in experimental clinical trials. Given the high prevalence of HIV infection in certain incarcerated populations, the issues surrounding clinical trials need clarification. A review of the history of prisoners as human subjects and current federal regulations regarding research on prisoners is provided. Experience at two New York State Designated AIDS Centers with inmates and experimental drug trials is described. Guidelines for enrollment of inmates in clinical trials are presented.

HIV-induced cytokine dysregulation, including overproduction of the antiproliferative and cytolytic IFN alpha cytokine, represents a major component of the immune disorders characterizing AIDS. To block the overproduction of IFN alpha we designed an AIDS vaccine combination which included both an anti-HIV and/or an anti-IFN alpha immunization. The safety and immunogenicity of this multicomponent vaccine were tested in mice, Cercopithecus, two HIV noninfected individuals, and six HIV-1 seropositive immunocompromised patients enrolled in a 1-year open clinical trial. We now report the result of a 9-month short-term randomized, blind, placebo-controlled clinical trial (Phase I/II) performed in HIV-1 patients (22 individuals) to confirm safety/tolerance of the anti-IFN alpha vaccine and its immunogenicity and to evaluate whether the complex vaccine initially used could be simplified by removal of HIV component(s). Three groups of patients received inactivated IFN alpha (i-IFN alpha) associated with the immunomodulator P40 with HIV-1 antigens (groups B and C) or without (group A), and one group (D) was placebo. The clinical follow-up documented among those receiving i-IFN-alpha showed that none developed AIDS and/or required antiretroviral chemotherapy. Viral load did not increase and CD4 cell count as well as cell-mediated immunity (CMI) stabilized or even significantly increased in group A. Immunogenicity of the preparations was determined by a positive delayed-type hypersensitivity (DTH) reaction to i-IFN alpha and the presence of serum antibodies to i-IFN alpha and to HIV-1 peptides, occurring only in treated patients. As previously planned, based on these safety data, the trial has been extended for an additional year and all patients were switched to protocol A (i-IFN alpha+P40). This second period of the trial, now open and ongoing, should allow us to evaluate further the innocuity of the i-IFN alpha preparation and whether anti-IFN alpha vaccine could provide a long-lasting CD4 cell count as well as CMI stabilization.