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The [beta]-chemokines RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein-1[alpha] (MIP-1[alpha]), and MIP-1[beta] are the natural ligands of the HIV-1 coreceptor CCR5 and compete with the virus for receptor binding. We show that secretion of the [beta]-chemokines by activated lymphocytes starts before cellular DNA synthesis is detected and demonstrate that transient prolongation of the [G.sub.1] phase of the cell cycle by treatment with cytostatic drugs results in increased levels of the three chemokines in culture supernatants. Supernatants collected from peripheral blood mononuclear cells exposed to hydroxyurea, which arrests the cell cycle in late [G.sub.1], contained high levels of [beta]-chemokines. These supernatants were able to inhibit HIV-1 replication when added to cultures of infected lymphocytes. The observed antiviral effect likely was due to the increased levels of [beta]-chemokines RANTES, MIP-1[alpha], and MIP-1[beta] because (i) supernatants greatly inhibited the replication of HIV-1 BaL, whereas they affected HIV-1 IIIb replication only slightly; (ii) neutralizing antibodies against the chemokines abrogated the antiviral effect of the supernatants; and (iii) the hydroxyurea concentrations shown to up-regulate chemokine levels were not sufficient to inhibit virus replication by depletion of intracellular nucleotide pools. Although antiviral properties have been reported previously for the cytostatic agents shown here to up-regulate [beta]-chemokine levels, our results provide an additional mechanism by which these drugs may exert antiviral activity. In summary, increased extracellular levels of anti-HIV-1 [beta]-chemokines resulting from transient prolongation of the [G.sub.1] phase of the lymphocyte cell cycle by treatment with cytostatic drugs may help to control the replication of CCR5-using strains of HIV-1.

The most effective weapon against viral diseases is immunization. It is not yet known, however, whether immunization will ultimately prove to be effective in the battle against AIDS. It is well established that patients infected with the AIDS virus (human immunodeficiency virus, HIV) develop antibodies against the virus, but these antibodies cannot prevent the ultimate progression of the disease. However, it may be possible to slow the progression of AIDS by assisting, with immunization, the production of antibodies in patients already infected with HIV. This possibility was evaluated in 30 subjects in the early stages of HIV infection. The patients were inoculated not with the AIDS virus, but with gp160. This protein is a part of the outer envelope of HIV; gp160 for inoculation purposes was prepared by cloning the gp160 gene and growing large quantities in the laboratory. The 30 subjects were divided into six groups; each group was vaccinated according to one of two schedules and at one of three different doses of vaccine. Measurements of the antibody response to gp160 showed that 19 of the 30 patients developed increased levels of antibodies in response to the immunization. A critical factor determining the response of the patient appears to be the stage of the disease. HIV-infected patients suffer a progressive loss of T cells with the CD4 antigen from their blood, and this loss serves as a useful measure of the progression of the infection. In the present study, 13 of the 16 subjects who still had more than 600 CD4 cells per milliliter of blood developed a successful antibody response, in contrast with 6 of the 14 subjects who had fewer than 600 CD4 cells per milliliter. It is too early to tell if the patients with a successful response to the gp160 vaccine will have a slower progression of disease. However, after 10 months the CD4 cell count has not decreased in the 19 patients who responded to immunization, while an average 7.3 percent decrease in the CD4 count was observed in the 11 subjects who did not respond. The results of this study indicate that the gp160 vaccine is safe and capable of eliciting an immune response in some HIV-infected patients. Furthermore, there is reason to suspect that the disease progression may be slower in the patients who responded successfully to immunization. (Consumer Summary produced by Reliance Medical Information, Inc.)

The prevalence of AIDS has been monitored since 1981, and the resulting information should help to predict the future course of this disease. However, the factors that determine infection with the human immunodeficiency virus (HIV), which causes AIDS, have changed within the past 10 years. The condition of AIDS is the clinical end stage of HIV infection and serves as an endpoint in surveillance studies, or studies that monitor AIDS epidemiology. The temporal, or time-related, trend in the incidence of AIDS reflects the history of HIV infection. This approach does not provide sufficient information about new cases of HIV infection over the past two to three years, a period of changes in the HIV epidemic. Direct measurement of the incidence of HIV infection would provide more accurate information about the HIV epidemic. However, the incidence of HIV infection can only be indicated by repeated testing for HIV antibodies, or the presence in the blood of immune proteins specifically directed against HIV. The groups that undergo routine testing for HIV antibodies include blood donors and United States military personnel. The temporal trend and demographic features of HIV seroconversion, or appearance of HIV antibodies, were assessed in United States Army personnel between November 1985 and October 1989. The results showed that 429 of 718,780 soldiers showed evidence of HIV seroconversion. The rates of seroconversion decreased between November 1985 and October 1989. The risk of HIV seroconversion was associated with race or ethnicity, age, sex, and marital status. It is estimated that about 220 soldiers were infected with HIV during 1989 and 1990, and the rate of HIV infection will probably decrease in the future. (Consumer Summary produced by Reliance Medical Information, Inc.)

The prevalence of AIDS (acquired immunodeficiency syndrome) in teenagers living in the United States is at present relatively low. Of all AIDS cases reported, approximately 0.4 percent have been in persons aged 13 to 19 years old. However, AIDS represents only the advanced stage of human immunodeficiency virus (HIV) infection, and the number of HIV-infected teenagers in this country is not known. As a follow-up to a survey conducted in October 1985 which assessed the prevalence of HIV infection in the US military, a similar survey was conducted which focused on HIV-infected individuals under the age of 20 years. The results of blood tests that were performed on 1,141,164 teenagers who applied for entry into the military between October 15, 1985 and March 31, 1989 were examined. Of this number, 393 applicants tested positive for HIV infection, which represented about one in every 3,000 (0.34 per 1,000) applicants nationwide. No significant difference in the frequency of HIV positivity was noted between the sexes (0.35 per 1,000 in males compared with 0.32 per 1,000 in females). However, blacks tested positive for HIV infection significantly more frequently than whites or Hispanics, at 1.06 per 1,000 compared with 0.18 per 1,000 in whites and 0.31 per 1,000 in Hispanics. A marked difference in prevalence was observed by geographic area. In the north-central states, the incidence was less than 0.1 per 1,000, compared with greater than 2 per 1,000 in urban counties of New York, the District of Columbia, Maryland, and Texas. Although the applicants to the military may not be representative of all teenagers nationwide, the data provide a basis for estimating the prevalence of HIV infection by geographic area and demographic groups. It is concluded that HIV infection is a real and immediate threat to US teenagers and it is not uncommon in this population, despite the fact that thus far, there have been few AIDS cases reported. (Consumer Summary produced by Reliance Medical Information, Inc.)