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In a study of genetic variation in the AIDS virus, HTLV-III/LAV, sequential virus isolates from persistently infected individuals were examined by Southern blot genomic analysis, molecular cloning, and nucleotide sequencing. Four to six virus isolates were obtained from each of three individuals over a 1-year or 2-year period. Changes were detected throughout the viral genomes and consisted of isolated and clustered nucleotide point mutations as well as short deletions or insertions. Results from genomic restriction mapping and nucleotide sequence comparisons indicated that viruses isolated sequentially had evolved in parallel from a common progenitor virus. The rate of evolution of HTLV-III/LAV was estimated to be at least 10(-3) nucleotide substitutions per site per year for the env gene and 10(-4) for the gag gene, values a millionfold greater than for most DNA genomes. Despite this relatively rapid rate of sequence divergence, virus isolates from any one patient were all much more related to each other than to viruses from other individuals. In view of the substantial heterogeneity among most independent HTLV-III/LAV isolates, the repeated isolation from a given individual of only highly related viruses raises the possibility that some type of interference mechanism may prevent simultaneous infection by more than one major genotypic form of the virus.

The clinical spectrum of human T cell lymphotropic virus type III (HTLV-III) disease is associated with myriad cutaneous findings, commonly of infectious origin. A clinically characteristic, yet histologically nonspecific, papular eruption was observed in seven of thirty-five patients followed up for HTLV-III disease (acquired immunodeficiency syndrome and the related complex). Noncoalescing 2- to 5-mm skin-colored papules of the head, neck, and upper trunk typify the lesions. Histologically, a chronic perivascular infiltrate of mononuclear cells was regularly present. The eruption was often, but not always, pruritic. The clinical course was chronic. Many patients had persistent lesions for more than 9 months; however, the number of papules tended to wax and wane with time. Although the cause of this eruption is unknown, it is sufficiently distinct and frequent to be recognized by clinicians as a cutaneous sign of human retrovirus infection.

In a study of the immunologic significance of the genetic diversity present within single isolates of human immunodeficiency virus type 1 (HIV-1), the neutralization of viruses derived from molecular clones of the HIV-1 strain HTLV-IIIB by an extensive panel of sera was compared. Sera from HIV-1-infected patients and from goats immunized with polyacrylamide gel-purified HIV-1 envelope glycoprotein (gp120), native gp120, or gp120-derived recombinant peptides, showed marked heterogeneity in neutralizing activity against these closely related viruses. The change of a single amino acid residue in gp120 may account for such "clonal restriction" of neutralizing activity.

Oral hairy leukoplakia (HL) is a newly described lesion occurring principally on the lateral borders of the tongue in immunosuppressed homosexual men infected with human T-cell lymphotropic virus type III (HTLV-III). Clinically, HL appears as a slightly raised, poorly demarcated lesion with a corrugated or "hairy" surface. Histologically, the lesion is characterized by keratin projections on the surface (which often resemble hairs), parakeratosis, and acanthosis. In addition, large pale-staining cells with pyknotic nuclei are seen in the upper stratum malpighii, which appear similar to the koilocytes described in uterine condylomata. Candida organisms are frequently observed on the lesion surface. Little, if any, subepithelial inflammation is present. Human papillomavirus and Epstein-Barr virus have been identified in biopsy specimens from lesions of oral HL. The association of this lesion in patients with HTLV-III infection has been established. We saw a patient with HTLV-III infection and HL, in whom the immunochemical and ultrastructural findings revealed the presence of a mixed viral infection. Because oral HL may be of diagnostic value as an early indicator of HTLV-III infection, awareness of its characteristic clinical, histologic, immunochemical, and ultrastructural features is important.

During the six months from October 1985 through March 1986, blood samples from 306,061 civilian applicants for military service from the United States were tested for antibody to the human immunodeficiency virus (HIV). Four hundred sixty subjects were positive for the antibody as determined by Western (immune) blot reactivity. The mean prevalence of HIV infection in this population of teenagers and young adults was thus 1.50 per 1000. According to multivariate analysis, the following demographic factors were found to be significant independent predictors of a positive HIV-antibody test: age (adjusted odds ratio = 1.10 per year), black race (adjusted odds ratio = 2.04), male sex (adjusted odds ratio = 1.84), residence in a densely populated county (adjusted odds ratio = 1.05 per 1000 per square mile), and residence in a metropolitan area with a high incidence of the acquired immunodeficiency syndrome (adjusted odds ratio = 1.53). Antibody-positive applicants were identified in 43 of the 50 states. Counties with high prevalence rates for HIV (greater than 5 per 1000) were located in New York State (four counties), New Jersey (three counties), California (two counties), Maryland (two counties), and Texas, Colorado, and Washington, D.C.

Suramin has been reported to inhibit the reverse transcriptase activity of a number of retroviruses and to reduce the in vitro infectivity and cytopathic effect of HTLV-III/LAV, the etiologic agent of acquired immune deficiency syndrome (AIDS). The clinical pharmacokinetics of suramin were investigated as part of a pilot study to evaluate the safety and efficacy of this drug for the treatment of patients with diseases caused by HTLV-III/LAV. A dose of suramin 6.2 g was given intravenously over a five-week period to four patients. After the last dose, the plasma half-life of suramin was 44 to 54 days. This is among the longest half-lives reported for any therapeutic substance given to humans. Total plasma levels of suramin were greater than 100 micrograms/mL for several weeks. In vitro activity of suramin was found at concentrations as low as 50 micrograms/mL. Metabolites were not found in plasma, and urinary excretion accounts for elimination of most of the drug. Suramin is approximately 99.7% bound to plasma proteins. The results from these initial clinical pharmacokinetic studies might assist the design of further therapeutic trials of suramin, especially the selection of frequency of dosing and adjustments for renal impairment.

Suramin was given to ten outpatients with acquired immunodeficiency syndrome (AIDS) presenting as Kaposi's sarcoma (KS) or as an AIDS-related complex (ARC). Side-effects associated with the administration of 6.2 g of suramin over 5 weeks included fevers, rashes, urinary abnormalities, and transient rises in hepatic aminotransferases. Peak serum levels of over 100 micrograms/ml were attained. There was evidence of HTLV-III infectivity and replication in lymphocytes from four patients before therapy. The detectable virus level fell in each case by the time of the last dose, and in three cases it became undetectable at the end of therapy. In each case, viral replication was again detected in the weeks or months following the administration of suramin. Despite this in-vivo virustatic effect, no significant clinical or immunological improvement was observed using this short-term regimen. However, the results provide a rationale for investigating longer-term regimens.

In a program screening civilian applicants for U.S. military service for human immunodeficiency virus (HIV) infection, we studied the frequency of false positive diagnoses retrospectively among applicants seropositive for HIV in a subpopulation with a very low prevalence of infection. That subpopulation was defined as consisting of all applicants tested between October 16, 1985, and June 30, 1987, who were young (17 or 18 years of age) and resided in a rural county in a state with a low incidence of reported acquired immunodeficiency syndrome (n = 135,187). Serum specimens from 15 applicants positive for HIV in this low-prevalence subpopulation were retrieved from a serum bank and retested by two Western blot methods, radioimmunoprecipitation, and an immunoassay constructed from a molecularly cloned and expressed viral envelope polypeptide. Fourteen of the 15 samples were unequivocally positive on all retest assays, and 1 was negative. Thus, the measured rate of false positive diagnoses in this program was 1 in 135,187 persons tested. Factors important in achieving a low false positive rate were redundant, multistep testing algorithm, conservative criteria for interpreting Western blots, the requirement that a second, newly drawn serum specimen be tested for verification before a diagnosis of HIV was considered established, and tight quality control of laboratory testing procedures. We conclude that a screening program for HIV infection in a low-prevalence population can have an acceptably low false positive rate.