Journal of acquired immune deficiency syndromes最新文献

To evaluate the effectiveness of bleach disinfection of injection equipment, we tested HIV-1 inactivation by household bleach in needles and syringes. We obtained blood from HIV-1 infected injecting drug users (IDUs), placed small aliquots in needles and syringes. Blood with and without anticoagulant was incubated at room temperature for 3, 6, 18, and 24 h, and some needles and syringes from each condition were exposed to undiluted bleach for 15 and 30 s. The needles and syringes were then rinsed and the rinses were used to inoculate peripheral blood mononuclear cells (PBMNCs). HIV-1 replication was monitored using p24 enzyme linked immunosorbent assay (ELISA). We describe results that HIV-1 is inactivated in clotted and unclotted blood allowed to stand at room temperature for 3, 6, 18, and 24 h in needles and syringes using undiluted household bleach at 30 s of exposure time. These results are consistent with earlier findings that micropellets of HIV-1 were inactivated by bleach under similar conditions of exposure to bleach; 10% bleach was not effective at an exposure time of 30 s and undiluted bleach was not effective at an exposure time of 15 s to inactivate HIV-1 in clotted blood. Bleach concentration and exposure time are critical and HIV disinfection may not occur with inadequate exposure to bleach HIV.

To examine the putative protective effect of disinfectant use on HIV seroconversion among injecting drug users, we conducted a nested case-control study of black heterosexuals comparing 34 HIV seroconverters with 154 persistent seronegatives matched on gender, cocaine injection (yes/no), date of study entry, and duration of follow-up. Injecting drug users who reported using disinfectant all the time had an odds ratio of seroconversion of 0.87, as compared with those who reported no use of disinfectants; the corresponding odds ratio was 1.00 for those who used disinfectants less than all the time. We examined the effect of drug use and sex practice variables, and responses to a socially desirable responding scale as possible confounders for the effect of needle disinfection on HIV seroconversion; the adjusted odds ratios for disinfectant use and HIV seroconversion were unchanged in this analysis. Despite limited statistical power and the potential for residual confounding, these data suggest that disinfection of injection equipment is not a substitute for abstinence from drugs or use of sterile injection equipment.

In 1986, community outreach workers began distributing small bleach bottles to injection drug users (IDUs) in San Francisco as a simple means for them to reduce their risk of infection with HIV and other pathogens by quickly flushing their syringes with bleach. At inception, the intervention was based on four assumptions: (a) sole reliance on expanded drug treatment capacity could not achieve HIV prevention goals, (b) legal barriers made syringe distribution or exchange schemes unfeasible, (c) IDUs would act in their own interest if the measures offered were acceptable to them, and (d) using bleach would diminish the risk of HIV transmission from reusing injection equipment. Following successful implementation of this program in San Francisco, similar programs were developed in many locations. These programs serve as the principal means of preventing needle-borne HIV infection among IDUs not enrolled in drug abuse treatment in the United States. Needed are definitive laboratory studies to determine the effectiveness of bleach decontamination as presently used by IDUs.

This study examined the effects of leukemia inhibitory factor (LIF) on human immunodeficiency virus (HIV) replication in mononuclear phagocytes (MNP). LIF induced a dose-dependent increase in p24 antigen production in the chronically infected promonocytic cell line U1. The magnitude and time kinetics of the LIF effects were similar to interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF), other cytokines known to induce HIV replication in this cell line. To characterize mechanisms responsible for these LIF effects, levels of HIV mRNA, activation of the DNA binding protein nuclear factor (NF)-kB, signal transduction pathways, and potential interactions with other cytokines were analyzed. LIF increased steady-state levels of HIV mRNA at 2.0, 4.3, and 9.2 kB. This was detectable by 24 h and persisted until 72 h. The DNA binding protein NF-kB is a central mediator in cytokine activation of HIV transcription. NF-kB levels were higher in unstimulated U1 cells as compared to the parent cell line U937. In both cell lines LIF increased NF-kB activity. Induction of NF-kB and HIV replication by cytokines are at least in part dependent on reactive oxygen intermediates. The oxygen radical scavenger N-acetyl-L-cysteine, but not an inhibitor of nitric oxide synthase, inhibited LIF-induced HIV replication. LIF induces the production of other cytokines in monocytes but its effects on HIV replication were not inhibited by antibodies to IL-1, TNF, or IL-6. These results identify LIF as a stimulus of HIV replication.(ABSTRACT TRUNCATED AT 250 WORDS)

The human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) Tat proteins Tat-1 and Tat-2 stimulate transcription of the viral long terminal repeat (LTR) sequences and are required for efficient viral replication. A class of mutant Tat proteins, termed "transdominant mutants," has been described that possesses relatively low transactivation activity, yet is able to inhibit the function of wild-type Tat. These mutant proteins contain a nonfunctional TAR RNA-binding domain but apparently retain a functional activation domain. A potential limitation for therapeutic use of transdominant mutants described to date is their low but significant basal level of transactivation for the HIV-1 or HIV-2 LTRs. In order to make an improved transdominant mutant, we have constructed Tat-2 proteins that contain mutations in four contiguous arginines at residues 81 to 84 in the RNA-binding domain. Using purified proteins and in vitro RNA-binding assays, we verified that these mutant Tat-2 proteins are defective for TAR RNA binding. We also verified that these mutant Tat-2 proteins bind to a cellular protein kinase in vitro that we have previously shown to bind specifically to the Tat-1 and Tat-2 activation domain. Using plasmid cotransfection assays, we compared the phenotypes of these mutant Tat-2 proteins with the most potent Tat-1 transdominant mutant described to date. One Tat-2 mutant, named "R81-84A," was found to be equivalent to the Tat-1 mutant in ability to inhibit wild-type Tat transactivation of HIV-1 and HIV-2 LTRs. Moreover, the R81-84A mutant possessed a significantly lower basal level of transactivation than the Tat-1 mutant. The R81-84A Tat-2 mutant is therefore a promising reagent for future development as an anti-HIV agent. Additionally, our results suggest that wild-type Tat-2 transactivation of the HIV-2 LTR is especially sensitive to inhibition by transdominant mutants.

This report describes experiments assessing the effectiveness against HIV of potential disinfecting agents that are commonly available to IDU when they are sharing syringes. We exposed cell-free HIV, HIV-infected cells, and HIV-infected blood containing known quantities of HIV to household cleaning agents, alcohols, peroxide, and highly acidic materials for 1 min, in order to examine the effects of these materials on the infectivity of the HIV. Undiluted liquid laundry bleach and dilute liquid dish detergent reduced the number of culturable HIV to an undetectable level under the experimental conditions used. Diluted bleach was not completely effective. Other potential disinfecting agents, including ethanol, isopropyl alcohol, and hydrogen peroxide, were unable to disinfect high numbers of HIV-infected cells or infected blood. Liquid dish detergent warrants further study as a possible acceptable alternative to bleach. Our data provide support for recommendations to IDU that they disinfect shared syringes every time between users with full-strength liquid laundry bleach to reduce their risk of acquiring or transmitting HIV. When bleach is not available, liquid dish detergent or other available disinfecting agents such as rubbing alcohol, hydrogen peroxide, or high alcohol content beverages are more effective than water at disinfecting HIV, recognizing that these materials are less effective than bleach. Although these materials are effective, they should not be viewed as a substitute for decreased sharing of injection equipment by IDU, or increased availability of sterile needles and syringes.