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An antisense version of an HIV RNA sequence might be a promising treatment for HIV infection. The RNA sequence is called the Rev response element, or RRE, because the viral Rev protein binds to it. Binding of Rev to RRE is crucial for HIV replication. Researchers showed that both sense and antisense versions of RRE inhibited viral reproduction in an HIV-infected cell line.

Some strains of HIV appear to inhibit other strains when both are present in T cells. The infection of a cell by one strain when the cell is already infected with another is called superinfection. Normally, HIV-infected cells resist superinfection, but several researchers have successfully superinfected cell cultures. One group has found that the RF strain of HIV can superinfect cells infected with the LAI strain. When this happens, the RF strain inhibits the LAI strain, possibly because it has a more active Tat protein and because of its integration site on the host DNA.

CD4+ T cells appear to be capable of reacting to several different amino acid sequences in the variable region 3 (V3) of the gp160 glycoprotein of HIV-1. The gp160 glycoprotein plays an important role in HIV infection. Researchers developed five T cell lines specific for the gp120 and gp160 viral proteins from four HIV-infected people. They measured the response of these T cell lines to truncated forms of the V3 region that contained different sequences, or epitopes. Each T cell line was activated by different epitopes, indicating that there is a cluster of epitopes against which T cells will react. However, the T cell lines did not react against V3 regions from different viral strains.

Vaccination with HIV-1 rgp160 may be effective in increasing the variety of antibodies HIV infected patients generate against the virus. Twenty-eight patients in the early stages of HIV infection received vaccinations of rgp160. Researchers used immunoblotting and PEPSCAN, a modified enzyme-linked immunosorbent assay (ELISA), to analyze levels of antibodies generated against various sections of the HIV envelope called epitopes. For patients who were followed for 12 to 20 months, the average reactivity to various epitopes regions increased. Reactivity to C2 increased from 0% to 46%, for C3 from 0% to 82%, for C1 from 62% to 100%. PEPSCAN on eight of the patients indicated new immune response to envelope epitopes V1, C3, and C5. Furthermore, the PEPSCAN method provides a way to measure antibody response to specific epitopes.

HIV patients who receive recombinant gp 160 (rgp 160) vaccine may produce more anti-HIV B-cell clones and may exhibit increased antibody production by the original B-cell clones. B cells are components of the immune system. Antibodies are produced in response to viruses, bacteria and other substances. The rgp 160 vaccine consists of a protein that is a precursor to two HIV proteins. Researchers studied immune responses in 30 HIV-infected people receiving the vaccine. Patients initially received between three and six shots. Blood samples were drawn from all HIV patients before and during the vaccination series to measure B-cell clones and anti-viral antibodies. Twenty-five patients had a measurable oligoclonal spectrotype with clear bands indicating an increase in B-cell antibody production. By increasing immune system response, post-infection vaccination may be useful in treating HIV-infected patients.

Only some cells infected with HIV may produce viral RNAs that can infect host cells and reproduce. Researchers compared cloned DNA (cDNA) and proviral DNA from a sample of peripheral blood mononuclear cells from an asymptomatic HIV-positive man. Proviral DNA is host DNA in which viral RNA has taken up residence and reproduced itself. The cDNA represented five viral genotypes recovered from the same blood sample. The genetic sequence of eight cDNA clones was different from that of the proviral DNA samples. Certain proviral genotypes may be expressed more often than others. Another possibility is that the immune response to the virus may favor some proviral genotypes over others, aiding their survival. Information about the most common viral genotypes will affect research on vaccines and HIV gene therapy.

New techniques allowing researchers to measure antibody to HIV in cerebrospinal fluid (CSF) may shed light on the activity of HIV in the nervous system. Using the standard peptide enzyme-linked immunosorbent assay (ELISA) technique as well as two novel techniques, called PEPSCAN and BIAcore, researchers measured and mapped the antibody produced in response to a sequence of amino acids called a V3 loop peptide in a common strain of HIV. In a study of 21 men with HIV disease, all showed the antibody specific to the V3 loop using these techniques. Measuring synthesis and activity of antibody inside the spinal cord sheath, as well as characterizing virus found in CSF, may illuminate the nervous system's mechanisms for regulating immune activity.

Patients with AIDS and HIV (human immunodeficiency virus) infection have various degrees of immune deficiency. When these patients receive vaccinations to protect them against common diseases, their antibody response is often inadequate, making the vaccination ineffective. In addition, the general safety of vaccinations in these patients is not clear. Twenty-one asymptomatic subjects who had tested positive for HIV antibodies and who had received a standard battery of vaccinations upon joining the Army were compared with 21 subjects who received the same vaccinations but who were not HIV-seropositive. Subjects were matched for age, sex, and race. All received a complete physical evaluation and blood work, and their response to each vaccine was measured. HIV-infected individuals, though asymptomatic, showed significantly weaker responses to vaccinations than did matched non-HIV-infected controls. This was true whether the vaccination depended on the action of T-cells (which are killed by HIV) or not. However, HIV-seropositive patients responded to booster immunizations (follow-up shots after previous vaccination) similarly to controls, indicating that response to vaccination may decrease as the disease progresses. It is recommended that HIV-infected patients be immunized as early as possible in the course of their disease so that a maximal immunological response can be obtained. There is no clear evidence that doing so is harmful to patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

An issue currently being discussed is whether persons who commit sexual crimes should undergo mandatory testing for infection with the human immunodeficiency virus (HIV). Paraphilic sex offenders have intense cravings for sexual behavior that not only deviates from the norm, but frequently involves inappropriate partners, such as children (pedophilia). Other examples of paraphilia include masochism and transvestism. In April 1990, the prevalence of antibodies to HIV was examined from blood samples from 77 paraphilic sex offenders. These offenders were being treated at the Sexual Disorders Clinic at Johns Hopkins Hospital in Baltimore, Maryland. Many of the offenders also engaged in more socially appropriate sex with consenting adult partners. Although the sexual behavior of the individuals included in the study necessarily involved actual or potential exchange of body fluids, which can increase the risk of spreading HIV, none of the 77 paraphilic sex offenders tested had antibodies to HIV (as determined by a test known as ELISA), indicating that they were not infected with the virus. (Consumer Summary produced by Reliance Medical Information, Inc.)

Human immunodeficiency virus (HIV, which causes AIDS) may lead to impaired immune function, even in HIV-infected individuals who have not developed symptoms of illness. The immunological responses against three types of vaccines were assessed in 21 individuals who had antibodies in their blood against HIV (HIV seropositive), but who did not have any symptoms of disease. Twenty individuals who did not have antibodies against HIV (HIV seronegative) served as controls. The three vaccines were: multiple, live but weakened, viral vaccines; viral protein molecules, known as toxoids; and viral sugar molecules. All of the seronegative individuals responded to two or more types of vaccines, compared with 48 percent (10 of 21) of the seropositive individuals. Fifty-two percent (11 of 21) of the seropositive subjects responded to only one of the three types of vaccines used. Laboratory tests revealed that the immune systems of the nonresponders were dysfunctioning. Abnormalities included defects in the functioning of helper T cells, defects in the suppression of the immune response, defects in B cells, and increased production of nonspecific antibody molecules. These abnormalities could be used to predict nonresponsiveness to the vaccines. These data suggest that in early stages of HIV infection, before clinical symptoms develop, many functions of the immune system are defective. This effect was observed in the weakened responses to the three types of vaccines. These findings must be taken into consideration when developing vaccines against HIV. (Consumer Summary produced by Reliance Medical Information, Inc.)

The human immunodeficiency virus (HIV) exists as two major types, 1 and 2. The CD4 molecule on the surface of host cells is the primary binding site for both viruses. However, research has now shown that there are some significant differences in the manner in which these two types interact with CD4. Since the viruses bind to CD4 in preparation for penetration and infection of the host cell, several schemes for treatment of HIV infection focus on blocking the viral binding sites with soluble CD4, which can be prepared in large quantities by the techniques of recombinant DNA. Experiments in tissue culture show that when the binding sites of HIV-1 are blocked by soluble CD4, infectivity is inhibited. However, HIV-2 seems to be more resistant to inhibition by this technique. The amount of soluble CD4 that induces the same degree of inhibition is from 50 to 400 times greater for HIV-2 than for HIV-1. However, antibodies against CD4 on the host cell surface equally inhibit the binding of both types, suggesting that HIV-2 is not evading the inhibition by CD4 simply by binding to an alternate receptor. The HIV-2 type was consistently found to have greater infectivity, and binding analysis using radioactively labelled virus revealed that fewer HIV-2 particles were bound to target cells at saturation compared with HIV-1. Both the reason for these differences and their clinical implications remain uncertain. (Consumer Summary produced by Reliance Medical Information, Inc.)

Although an enormous amount of information is known about HIV (human immunodeficiency virus), the virus which causes AIDS (acquired immunodeficiency syndrome), the techniques available to inhibit HIV from causing infection are still limited. A new agent which has potential use in the treatment of HIV infection is a soluble form of CD4, the receptor on T lymphocytes to which the virus binds, allowing it to enter the cell. The theory behind the use of soluble CD4 is that the virus will bind to the soluble CD4, which has been injected into the bloodstream of infected individuals in large quantities and circulates freely. It is hoped that all of the virus will bind to the soluble receptors and there will be no virus left to bind to the CD4 which is present on the surface of healthy cells. In this way, infection of body cells would be prevented. However, the practical application of this theory is complicated. The immune system might recognize the soluble CD4 as foreign, creating an immune response to it and to the T cells that naturally contain it. This could cause destruction of the T cells, which are necessary for an immune response against the virus, making the condition of the patient worse. An immune response to the soluble receptor could also cause suppression of the immune system, inhibiting a response against the virus. However, phase I trials to test soluble CD4 have been promising, showing that concentrations up to 30 milligrams a day do not adversely affect the immune system. Further study is necessary in many areas of the therapy including: the modification of CD4 so that it can be administered more effectively to maintain high blood levels; long-term toxicity; and addition of substances to CD4 to make it toxic to the virus. The most effective therapy against the development of AIDS would be one that inhibited the virus at different phases of its life cycle. The use of soluble CD4 could be an important part of that therapy. (Consumer Summary produced by Reliance Medical Information, Inc.)