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Almost all investigations examining the effects of early HIV infection on neuropsychological functioning in homosexual males have excluded subjects with cognitive risk factors such as recreational drug use and head injury. While insuring that results reflect the influence of the virus on cognition, this selection bias limits the ability to generalize findings. Comprehensive neuropsychological evaluations were compared between two groups of homosexual males with a variety of cognitive risk factors. Subjects were 132 HIV seropositive males (108 CDC class II & III and 24 CDC class IVA & IVC2) and 65 HIV seronegative controls. Recreational drug use in the six months prior to exam was found to interact with HIV infection and was associated with selective areas of cognitive decline and a significantly worse overall neuropsychological performance. Although significantly lower functioning in the domains of Verbal Memory and Attention and Speed of Information processing was noted for subjects with CDC class IVA and IVC2 compared to seropositives with CDC class II & III, overall neuropsychological performance was similar in these two groups. At this early stage of HIV infection, we did not find indication of association between neuropsychological performance and decreased immunological status. A history of head injury and recent recreational drug use emerged as primary cognitive risk factors associated with decreased neuropsychological performance. As 50% of our HIV seropositive subjects reported active recreational drug use, this cognitive risk factor in particular may contribute to the appearance of HIV-related cognitive deficits during early stages of HIV infection.

The efficacy of two doses of zidovudine was examined for the treatment of the acquired immunodeficiency syndrome (AIDS) dementia complex in a randomized, double-blinded, placebo-controlled trial conducted at nine study centers. For the initial 16 weeks, 40 subjects with mild to moderate AIDS dementia complex were randomized to one of three treatment arms: 400 mg of zidovudine five times daily, 200 mg of zidovudine five times daily, or placebo five times daily. After week 16, patients initially randomized to the placebo group were rerandomized to one of the two zidovudine treatment arms. The primary efficacy end point was improvement in performance on a battery of seven neuropsychological tests; the secondary end point was improvement on a protocol neurological evaluation directed at the cardinal features of the AIDS dementia complex. For the initial 16-week period, average z scores based on the neuropsychological test battery revealed a significant improvement in the combined treatment groups compared to the placebo group; however, when the two treatment groups were compared separately to the placebo group, only the group receiving the higher zidovudine dose exhibited significant improvement. After rerandomization of the placebo patients to one of the two treatment arms at week 16, this group also showed significant improvement in the average neuropsychological z score by week 32. These results extend previous observations that indicate a therapeutic benefit of zidovudine for the treatment of AIDS dementia complex.

Transmission studies have suggested that an optimal human immunodeficiency virus type 1 (HIV-1) vaccine should induce both neutralizing antibodies and cytolytic T cells to eliminate free virus and infected cells. A phase I trial in healthy HIV-1-seronegative persons was conducted with a combination HIV-1 vaccine regimen (strain IIIB) consisting of priming with a recombinant vaccinia (vac/env) virus expressing HIV-1 envelope and boosting with a gp160 glycoprotein derived from a recombinant baculovirus (rgp160). T-cell and antibody responses detected after immunization with either vac/env alone or rgp160 alone were generally of low magnitude and transient, and no subject developed neutralizing antibodies. In contrast, recipients of the combination regimen demonstrated in vitro T-cell proliferative responses to homologous HIV-1 antigens that were 3- to 10-fold higher than responses with either vaccine alone, and these responses were sustained for > 18 months in 75% of recipients. Moreover, both CD8+ and CD4+ cytolytic T cells were detected. Antibody responses (titer, 1:800 to 1:102,400) to homologous HIV envelope developed in all recipients of the combination regimen, and neutralizing antibodies were detected in 7 of 13. Thus, immunization with a live virus vaccine followed by boosting with a soluble protein offers promise for inducing the broad immunity needed in an HIV vaccine.

Purpose: As part of a longitudinal study of human immunodeficiency virus type 1 (HIV) infection, we attempted to identify early cerebral MR findings that might correlate to clinical evidence of central nervous system involvement., Methods: We studied 65 seropositive and 40 seronegative homosexual males using cranial MR, neurologic, immunologic, and neuropsychologic examinations., Results: The incidence of mildly enlarged ventricles, sulci, and punctate areas of abnormal signal in both groups was similar in both groups. Diffuse, poorly defined areas of abnormal white matter signal were difficult to consistently identify in seropositives. Enlarged adenoidal lymphoid tissue was found in 30 (46%) of seropositives and 2 (5%) of seronegatives (P = .0001). The incidence of sinus inflammatory change was similar in the two groups., Conclusion: MR of intracranial contents is substantially normal in a non-AIDS HIV(+) population.

To determine safety and efficacy of tumor necrosis factor (TNF) and interferon-gamma (IFN gamma) in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related complex, a randomized, double-blind study was conducted. Twenty-five patients with AIDS-related complex and CD4 lymphocytes less than or equal to 500 x 10(6)/L attended an AIDS Clinical Trials Unit of a tertiary referral center. Patients were administered tumor necrosis factor (TNF) (10 micrograms/m2) or IFN gamma (10 micrograms/m2), or both intramuscularly three times weekly for 16 weeks. Side effects from all three preparations included fever, constitutional symptoms, and local reactions. No significant hematologic, hepatic, renal, or coagulation abnormalities were observed. CD4 lymphocyte counts, beta 2-microglobulin, p24 antigen levels, and anti-p24 antibody did not change significantly during therapy. Similarly, no significant change was noted in rates of HIV isolation from peripheral blood mononuclear cells or plasma. TNF and IFN gamma were tolerable after premedication with acetaminophen; however, no significant change in markers of human immunodeficiency virus infection was demonstrated. These cytokines alone do not appear to be of benefit, nor do they appear to hasten the progression of HIV infection.

Recombinant soluble CD4 covalently linked to an immunoglobulin G heavy chain (rCD4-IgG) was evaluated clinically for the treatment of human immunodeficiency virus infection. The interference of rCD4-IgG with the measurement of peripheral blood CD4 lymphocytes by whole-blood lysis flow cytometric analysis was investigated using three commercial monoclonal antibody reagents. Addition of rCD4-IgG resulted in an artifactual decrease in measured CD4 number at rCD4-IgG levels of greater than or equal to 1 micrograms/mL; the threshold for this decrease was dependent on the concentration of monoclonal antibody in the commercial preparation used for the measurement of CD4. This artifactual decrease in CD4 cell count was observed in two patients who received rCD4-IgG intravenously. The apparent decrease in CD4 count was eliminated with the use of a single phosphate-buffered saline wash step before the addition of monoclonal antibody. rCD4-IgG can bind to anti-CD4 antibody and lower the measured CD4 cell count in vitro; this interference can be eliminated by a single or a double wash step and is necessary when using the whole-blood lysis flow cytometric technique of enumerating CD4 lymphocytes in patients receiving rCD4-immunoglobulin G.

To characterize neurological and neuropsychological findings associated with human immunodeficiency virus type-I (HIV) infection, 77 seropositive homosexual or bisexual males with no or minor symptoms of HIV were compared prospectively to 44 HIV seronegative men by observers blinded to serological status of the subjects. Neurological symptoms and examination findings were not significantly different between seropositives and seronegatives except for cranial nerve findings, predominantly mild hearing impairment. Mean performance scores for a 15-test neuropsychological battery were within an unimpaired range for both groups, although for five tests, mean scores were significantly poorer in seropositives. After adjustment for vocabulary score, and demographic and psychosocial variables, the mean score of seropositives was significantly worse only for the Benton Visual Retention Test. Magnetic resonance (MR) images of brain were abnormal in 14 (27%) of 52 seropositives and one of 10 seronegatives (value was not significant). HIV was isolated from cerebrospinal fluid (CSF) in 31 (61%) of 51 seropositives. The only clinical or laboratory difference between CSF culture positives and negatives was a higher CSF immunoglobulin synthesis rate in the former subjects (medians of 10.3 versus 0.1 mg/day; p = 0.03). An additional 13 seropositive subjects had immunologic evidence of central nervous system HIV infection, defined by a serum-to-CSF HIV antibody ratio of less than 5.5. Intracranial abnormalities on MR imaging were associated with CSF immunologic responses to HIV. Nervous system involvement occurred in the vast majority of men with early HIV infection, but clinically significant impairment was uncommon.

The pharmacokinetics of zidovudine were evaluated in 41 patients with Centers for Disease Control HIV class IVA infection. The patients were assigned escalating doses of zidovudine (300, 600, or 1,500 mg daily) and were randomized to receive either zidovudine alone or zidovudine with a high dose of acyclovir (4,800 mg per day). Single and multiple intravenous- and oral-dose pharmacokinetic studies were performed on days 1 and 7 and weeks 6 and 12 of therapy. Zidovudine concentrations were analyzed by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods. Zidovudine concentrations in serum declined in a biphasic manner, with half-lives ranging from 1 to 2 h, and were independent of acyclovir administration or length of zidovudine therapy. The median time of peak concentrations in serum following oral doses was 0.75 h (range, 0.25 to 3 h). Accumulation of zidovudine in serum was not observed, but the maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve increased proportionally with increased zidovudine doses. Mean day 7 oral Cmax values were 0.20 +/- 0.12, 0.55 +/- 0.33, and 1.0 +/- 0.5 micrograms/ml for 17 patients receiving total daily doses of, respectively, 300, 600, and 1,500 mg of zidovudine alone, whereas Cmax values were, respectively, 0.27 +/- 0.18, 0.43 +/- 0.33, and 1.2 +/- 0.80 micrograms/ml for 15 comparably treated recipients of zidovudine plus acyclovir (P was not significant). The median bioavailability of oral zidovudine was 67% (42 to 120%) and did not vary with dosage. Absolute and apparent total body clearances were similar among the patients given the various zidovudine doses regardless of whether there was concomitant acyclovir therapy. Drug-related toxicities were observed more frequently in the subjects who received high doses of zidovudine than they were in those who received median and low doses of zidovudine (P=0.03). Overall, acyclovir did not influence the disposition of zidovudine over a wide range of zidovudine doses. No unusual toxicities could be attributed to the zidovudine and high-dose acyclovir combination during the 12-week observation period.

The effect of human immunodeficiency virus type 1 (HIV) infection on semen parameters that assess fertility was investigated in 50 semen specimens from 21 asymptomatic or minimally symptomatic HIV-seropositive men and 3 specimens from 3 men with AIDS. HIV was isolated from 15 (30%) of 50 specimens from asymptomatic or minimally symptomatic persons and from 1 of 3 specimens from patients with AIDS. The men with AIDS all had pyosemia and grossly abnormal sperm. In contrast, semen specimens from other seropositive men did not differ significantly from semen specimens from healthy seronegative semen donors. No abnormality in sperm count, morphology, numbers or types of leukocytes in semen, or other seminal parameters was associated with HIV shedding in semen. Zidovudine therapy did not affect sperm morphology or seminal characteristics. Thus, although patients with AIDS had abnormal semen, the laboratory parameters that assess fertility were not affected by shedding of HIV in semen or concomitant therapy with zidovudine.

Fifty-two patients with acquired immunodeficiency syndrome were enrolled in this study to evaluate the relationship between cerebrospinal fluid (CSF) zidovudine concentrations and neurologic and human immunodeficiency virus (HIV) culture findings. Paired HIV-CSF culture and neurologic measurements were available in 30 and 45 patients, respectively. Twenty-nine patients were assessable for zidovudine CSF concentrations. Patients underwent lumbar puncture and neurologic testing before and after 8 weeks or more of oral zidovudine therapy (600 to 1500 mg/d). After 8 weeks of therapy, the frequency of HIV isolation from CSF cultures was unchanged. Significant neurologic improvement by examination was noted in 61.5% (32/52) of the patients. The median CSF zidovudine concentration among 29 patients was 0.047 mg/L (range, 0.015 to 0.198 mg/L). No correlation between CSF zidovudine concentration, cumulative dose, or HIV isolation from CSF and persistence or resolution of neurologic symptoms or signs was observed. The mechanisms by which zidovudine improves neurologic function are unclear and appear unrelated to direct clearance of virus from CSF.

In a randomised phase I trial of a recombinant vaccina virus vaccine expressing the gp160 envelope gene of the human immunodeficiency virus (HIVAC-1e) 35 healthy, HIV-seronegative males, 31 of whom had a history of smallpox immunisation and 4 of whom were vaccinia naive, were vaccinated and then boosted 8 weeks later with HIVAC-1e or standard NY strain vaccinia virus. The frequency, duration, and titre of virus isolation from the vaccination site and occurrence of local side-effects were similar between the two groups of vaccinees. Vaccinia-naive (vac-n) subjects shed virus from the vaccination site for longer and at a higher titre than did vaccinia-primed (vac-p) individuals (19 vs 7 days and 10(7) vs 10(5) pfu/ml, respectively). In-vitro T-cell proliferative responses to one or more HIV antigen preparations developed in 13 of 16 vaccinia-primed subjects inoculated with HIVAC-1e. T-cell responses were, however, transient and in no subject did antibodies to HIV become detectable. The 2 vaccinia-naive subjects vaccinated with HIVAC-1e showed strong T-cell responses to homologous and heterologous strains of whole virus and to recombinant gp160 protein that remained detectable for over a year; antibodies to HIV envelope also developed in both. Recombinant vaccinia virus vaccines induce T-cell priming to the foreign gene products in most individuals. If used as the sole immunising agent they will be most efficacious in vaccinia-naive individuals.

Because exposure to semen is important for the sexual transmission of human immunodeficiency virus type 1 (HIV), the relationship of stage of infection and antiviral chemotherapy to isolation of HIV from semen was investigated. Whereas HIV was isolated from peripheral blood mononuclear cells of all seropositive persons tested, it was isolated from semen in only 11 (32%) of 34 men, including 3 of 6 who were studied sequentially over time. HIV was isolated from 6 (32%) of 19 semen specimens from 14 asymptomatic persons (Centers for Disease Control [CDC] class II or III) and from 10 (28%) of 36 semen specimens from 20 symptomatic patients (CDC class IV). Isolation of HIV from semen did not correlate with CD4+ or CD8+ T lymphocytes counts or zidovudine therapy. Seropositive men may shed HIV in semen early in the course of infection, and zidovudine therapy seems to have no effect on the recovery of HIV and, thus, on the potential for sexual transmission of HIV.

Background: The initially tested dose of zidovudine for the treatment of patients with advanced disease caused by the human immunodeficiency virus type 1 (HIV) was 1500 mg. Although this dose is effective, it is associated with substantial toxicity., Methods: To evaluate the efficacy and safety of a reduced dose, we conducted a randomized controlled trial in 524 subjects who had had a first episode of Pneumocystis carinii pneumonia. The subjects were assigned to receive zidovudine in either a dose of 250 mg taken orally every four hours (the standard-treatment group, n = 262) or a dose of 200 mg taken orally every four hours for four weeks and thereafter 100 mg taken every four hours (the low-dose group, n = 262)., Results: The median length of follow-up was 25.6 months. At 18 months the estimated survival rates were 52 percent for the standard-treatment group and 63 percent for the low-dose group (P = 0.012 by the log-rank test). At 24 months the estimated survival rates were 27 percent for the standard-treatment group and 34 percent for the low-dose group (P = 0.033). In both groups, 82 percent of the subjects had another opportunistic infection, and the length of time to that infection was similar in the two groups (P = 0.56 by the log-rank test). CD4 T-lymphocyte counts improved transiently in both groups, and serum levels of HIV antigen decreased in the subjects with antigenemia. The hemoglobin level declined to less than 5 mmol per liter (80 g per liter) in 101 subjects in the standard-treatment group and in 77 in the low-dose group (39 vs. 29 percent, P = 0.0009 by the log-rank test). The neutrophil count declined to less than 0.750 x 10(9) per liter in 134 subjects in the standard-treatment group and in 96 in the low-dose group (51 vs. 37 percent, P = 0.0001)., Conclusions: The reduced daily dose of zidovudine used in this study was at least as effective as the standard dose and was less toxic; however, with the use of a four-week induction period with a high dose followed by low-dose treatment, severe anemia and neutropenia were common complications of treatment with zidovudine.

Background: Zidovudine delays the progression of human immunodeficiency virus (HIV) infection but is associated with hematologic toxicity at high doses. Regimens are needed that preserve or enhance efficacy and reduce toxicity. Acyclovir has been reported to potentiate the effect of zidovudine on HIV in vitro., Methods: We conducted a Phase II open-label, dose-escalating trial to evaluate the clinical and antiviral effects of zidovudine at low (300 mg daily, 28 subjects), medium (600 mg, 24 subjects), and high (1500 mg, 15 subjects) doses, either with or without acyclovir (4.8 g) by random assignment. The subjects had the acquired immunodeficiency syndrome (AIDS)-related complex, but not AIDS. All of them had either HIV p24 antigenemia or plasma viremia and CD4-lymphocyte counts of 200 to 500 per cubic millimeter when they began treatment., Results: Performance scores and fatigue improved the most in the low- and medium-dose zidovudine groups (both P less than or equal to 0.025). Those assigned to low-dose zidovudine gained the most weight and had the greatest improvement in the mean CD4-lymphocyte count (from 321 per cubic millimeter at base line to 412 per cubic millimeter after 12 weeks, P = 0.01). The proportion of subjects in whom HIV antigenemia resolved, the decrease in the level of antigenemia, and the reduction in the plasma virus titers were similar at all three doses. Subjects assigned to receive the low or medium dose who subsequently crossed over to the 1500-mg dose (n = 19) did not have an increase in CD4-cell counts or a decline in levels of HIV antigen, but they did have dose-related toxicity. The addition of acyclovir to zidovudine was well tolerated, but it did not enhance any of zidovudine's antiretroviral effects., Conclusions: In this pilot study a very low dose of zidovudine (300 mg) had clinical and virologic effects similar to those of higher daily doses (600 and 1500 mg). The minimal effective dose of zidovudine for the treatment of HIV infection has yet to be determined, and further studies of very low daily doses are warranted.

To evaluate prospectively the relationship between current and past sexual practices and seroprevalence of cytomegalovirus (CMV) in adult women, 1481 women (1101 white, 301 black, 79 other) attending a sexually transmitted disease clinic underwent a standardized interview and genital examination. CMV seroprevalence was higher in black (78%) than in white (59%) women. In logistic regression models that adjusted for age and years of education, CMV seropositivity in white women was associated with younger sexual debut (P = .001), more lifetime sex partners (P = .025), recent new partner(s) (P = .003), and parity (P = .002), and was inversely associated with use of barrier contraception (P = .006). In black women, after adjustment for demographic characteristics, CMV antibody was associated with greater numbers of recent sex partners (P = .007), new sex partners (P = .04), and with cervical infection with Chlamydia trachomatis (P = .05). This study confirms that sexual activity is an important determinant of CMV infection in both white and black women; however, the relative contributions of sexual and nonsexual transmission of CMV apparently vary and require further investigation.

Objective: To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection., Design: A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts., Setting: Multicenter trial at AIDS Clinical Trial units., Subjects: Seven hundred eleven subjects with mildly symptomatic HIV infection., Intervention: Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months., Measurements and Main Results: Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively., Conclusion: Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.

The role of age-dependent responses in infantile amnesia was examined. Ten- and 15-day old rats were trained in an approach-mother, avoid-shock paradigm and tested for retention immediately and after a 1-day delay. Ten-day-old rats were also tested after 6 days. Half of all the pups received a shock reactivation treatment before the delayed retention tests and half did not. In comparison to immediate retention, performance declined after 1 day but was reinstated by reactivation. A similar reactivation effect was found on 10-day-old pups tested after 6 days except that a different age-specific response was substituted for the original behavior. These effects were not found in untrained controls. These data show that learning may be expressed differently when acquisition and retention are measured at different developmental stages, a pattern that may be mistaken for infantile amnesia.

Zidovudine is the only drug currently approved for the treatment of HIV infection. The present recommended doses found to be efficacious in patients with AIDS (200 mg every 4 h) achieve serum zidovudine concentrations greater than 0.267 micrograms/ml (1 mumol/l). Since patients often take zidovudine with food, we have investigated the effect of a liquid high-fat meal on the rate of absorption of zidovudine and on the peak serum concentration achieved. Eight patients received their usual dose of zidovudine (100 mg or 250 mg), with and without a liquid high-fat meal, on two separate study days, in a randomized crossover fashion. Blood and urine samples were collected over a 4-h period. In the absence of food, zidovudine is rapidly absorbed; the time to reach maximal serum concentration (Tmax) was 0.68 (+/- 0.25) h and the mean peak serum concentration (Cmax) achieved was 0.49 (+/- 0.3) micrograms/ml (dose normalized to 100 mg dose). In the presence of a high-fat meal, Tmax was significantly prolonged [1.95 (+/- 0.69) h; P less than 0.05] and the Cmax reduced [0.245 (+/- 0.12) micrograms/ml; P less than 0.05]. This demonstrates that to achieve maximal zidovudine serum concentrations, patients should take this medication on an empty stomach.

Zidovudine (azidothymidine, AZT) disposition was examined during a hemodialysis session in an HIV-infected male with mesangial proliferative glomerulonephritis. Serum concentrations of zidovudine and its glucuronidated inactive metabolite (G-ZDV) were measured by HPLC. Zidovudine pharmacokinetics were similar to previous reports in patients with normal renal function, however, G-ZDV concentrations were significantly elevated (23-440 times zidovudine concentration). Hemodialysis did not appreciably reduce zidovudine or G-ZDV levels. Significance of chronically elevated G-ZDV levels is unknown.

Study Objectives: To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum, and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement., Patients: Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period., Interventions: Lumbar puncture was done on all patients. Rabbit inoculation was used to test cerebrospinal fluid for viable T. pallidum. Patients with normal fluid received recommended benzathine penicillin therapy according to the stage of syphilis; patients with CSF abnormalities were offered 10-day therapy for neurosyphilis., Results: Treponema pallidum was isolated from the CSF of 12 (30%) of 40 patients (95% CI, 17 to 46) with untreated primary and secondary syphilis; isolation of T. pallidum was significantly associated (P = 0.008) with the presence of two or more abnormal laboratory variables (among leukocyte count, protein concentration, and CSF-Venereal Disease Research Laboratory [VDRL] test). Two (67%) of 3 early latent (CI, 13 to 100) and 3 (20%) of 15 late latent syphilis patients (CI, 5 to 47) also had reactive CSF-VDRL tests and elevated cell and protein levels, although T. pallidum was not isolated. Concurrent infection with the human immunodeficiency virus (HIV) was not associated with isolation of T. pallidum, increased number of CSF abnormalities, or reactive CSF serologic tests for syphilis, although CSF pleocytosis was commoner in subjects infected with HIV. Treatment with conventional benzathine penicillin G (2.4 mIU) failed to cure 3 of 4 patients with secondary syphilis from whom T. pallidum was isolated before therapy; all 3 patients in whom treatment failed were HIV seropositive when treated or seroconverted during follow-up., Conclusions: Central nervous system invasion by T. pallidum is common in early syphilis, and is apparently independent of HIV infection. Examination of the CSF may be beneficial in patients with early syphilis, and therapy should be guided by knowledge of central nervous system involvement. Conventional benzathine penicillin G therapy may have reduced efficacy in patients with early syphilis who are also infected with HIV.

The acquired immune deficiency syndrome (AIDS) has been reported in more than 2800 persons in the United States (70 per cent of whom are homosexually active men). AIDS is manifested by impaired cell-mediated immunity that results in various opportunistic infections (especially pneumonia caused by Pneumocystis carinii) or malignant disease (especially disseminated Kaposi's sarcoma). The cause is unknown, and effective treatment is not yet available. AIDS apparently is not highly infectious for persons outside the acknowledged high-risk groups.

Persistent, generalized lymphadenopathy (PGL) is a recognized component of human immunodeficiency virus (HIV) infection. We conducted longitudinal studies of B and T cell function in seven homosexual men with HIV infection and PGL. All seven had abnormal antibody-mediated immunity as studied by sequential assessment of in vivo antibody responses after immunization with the T-dependent neoantigens bacteriophage phi X 174 and keyhole limpet hemocyanin (KLH), the T-independent tetradecavalent pneumococcal polysaccharide vaccine, and the recall antigens diphtheria and tetanus toxoid. Compared to HIV-negative heterosexual controls, PGL patients responded with lower antibody titers and, following immunization with phage, failed to develop immunologic memory and to switch from IgM- to IgG-isotype antibody. In vitro antigen-induced antibody production was markedly diminished; and some patients showed depressed mitogen responses. There was a correlation between the degree of compromised immunity and the clinical condition; those with the most severe symptoms showed the most extensive immune deficiency. Yet despite obvious immunologic impairment five of the seven men have remained clinically stable over a 3-year follow-up period.

Behavioral observations were made on the reaction to tailshock and footshock in 5- to 20-day-old hooded rats. For detection thresholds, age differences were found for footshock but not for tailshock. During intershock intervals, more generalized activity and freezing were elicited by footshock, whereas more responding directed to the shock source was elicited by tailshock. The unconditional responding to shock indicated that the older animals had a larger behavioral repertoire of defensive reactions and responded differentially to different shock intensities. The younger animals appeared to have a more limited and stereotyped repertoire of defensive reactions and to be more sensitive to the same nominal shock level. These normative data should prove useful in evaluating motivational and response repertoire problems when assessing learning processes developmentally.

That organisms cannot remember events occurring during infancy may be the result of common forgetting processes exacerbated by the organism's increase in size during development or a unique process such as insufficient neurological development at the time of the early experience. To establish the uniqueness of infantile forgetting, size change was made irrelevant by exposing infant rats to "off-baseline" Pavlovian fear conditioning and assessing the effect of an apparatus-free conditioned stimulus upon independently established bar pressing. In Experiment 1, bar pressing by rats exposed to Pavlovian contingencies when 20-22 days old was substantially suppressed by the conditioned stimulus both 1 and 42 days after conditioning. In Experiment 2, pups conditioned when 17-19 and 20-22 days old again showed excellent retention, whereas pups conditioned when 11-13 and 14-16 days old showed total forgetting 42 days later. In Experiment 3, pups conditioned when 14-16 days old remembered well after 5 days, less well 10 days later, and not at all after 20 days. These findings suggest that size change may contribute to the forgetting of events occurring late in development, but that neurological immaturity may underly the forgetting of earlier events.

Plasma corticosterone fluctuations of infant rats were examined in a learning task. A blood sample for analysis of plasma corticosterone was collected from groups of 10- and 15-day-old pups following either no disturbance, standard maternal deprivation only, or deprivation and training in an established approach-mother, avoid-shock conflict task. In the latter condition, pups remained in the goalbox either alone or with an anesthetized dam for either 15 or 60 min before blood sample collection. Plasma corticosterone levels were elevated following deprivation plus training in pups of both ages and following deprivation only in the 15-day-old pups. Further, the presence of the dam in the goalbox reduced plasma corticosterone elevations, particularly among 15-day-old pups and at 60 min. These findings suggest that the mother's capacity to moderate the pup's plasma corticosterone response may contribute to her reinforcement value in infant-learning paradigms.

Antiviral agents under investigation for the treatment of patients infected with the human immunodeficiency virus (HIV) are reviewed. Multiple mechanisms exist by which antiviral agents might inhibit the replication of HIV or eradicate its latent form in affected cells, or both. These mechanisms include (1) interference with the cell surface receptor for HIV, (2) prevention of uncoating of viral particles, (3) inhibition of reverse transcriptase, (4) prevention of integration and posttranscription processing, (5) interference with viral assembly, and (6) interference with virus release. Most agents developed thus far work by inhibiting HIV reverse transcriptase. Suramin, ribavirin, ammonium 21-tungsten-9-antimoniate (HPA-23), foscarnet (phosphonoformate, PFA), inosine pranobex (isoprinosine), peptide T, ampligen, AL 721, dideoxycytidine, and zidovudine (formerly azidothymidine) have antiretroviral activity in vitro. To date zidovudine is the only antiretroviral agent approved by the FDA as clinically effective. However, zidovudine has serious toxicities, including neutropenia and anemia; in some patients dosage reduction or cessation of therapy may be necessary. Because treatment with zidovudine does not cure HIV infection, numerous studies are under way with other anti-HIV agents. Ultimately, combinations of agents probably will be used to suppress or eradicate HIV. While the search for more efficacious and less toxic treatments continues, the development of zidovudine in such a short time provides hope that progress toward a cure will be made rapidly.

To determine which markers of human immunodeficiency virus type 1 (HIV) replication correlate most closely with progressive disease, we compared the following: (1) the frequency of isolation of HIV from peripheral-blood mononuclear cells (PBMC), (2) the frequency of isolation of the virus from cell-free plasma (plasma viremia), (3) the presence and titer of p24 antigen in plasma, and (4) the presence and titer of antibody to p24 antigen. We studied 213 persons who were positive for HIV antibody and 71 who were negative. HIV was isolated from PBMC from 207 of the 213 antibody-positive patients (97 percent), regardless of the clinical stage of the infection. Plasma viremia, in contrast, was correlated with the clinical stage of the infection. It was detected in 11 of 48 patients (23 percent) with asymptomatic infection, 32 of 71 (45 percent) in Class IVa of the Centers for Disease Control (those with AIDS-related complex), and 75 of 92 (82 percent) in Class IVc (those with AIDS) (P less than 0.01). Plasma HIV titers ranged from 10(0) to 10(4.3) and rose from a mean of 10(1.4) in asymptomatic patients to 10(2.5) in those with AIDS (P less than 0.02). Only 45 percent of patients with plasma viremia had HIV p24 antigen in either serum or plasma, and no correlation was found between the amount of p24 antigen in plasma and the plasma HIV titers. Follow-up tests indicated that plasma viremia was associated with a more marked decline in the CD4-lymphocyte cell count and the development of symptomatic disease (P = 0.034). We conclude that plasma viremia is a more sensitive virologic marker of the clinical stage of HIV infection and viral replication than the presence of p24 antigen or antibody in plasma. Not only whole blood but cell-free plasma from HIV-infected patients should be considered potentially infectious.

This report describes the case of a homosexual man with non-Hodgkin's lymphoma, whose primary complaint involved his ocular system.

The prevalence of antibody to LAV/HTLV-III among homosexual men attending a community clinic and a sexually transmitted disease clinic in Seattle, Washington in early 1985 was 42 per cent and 32 per cent, respectively. Seropositivity was apparently not related to age or number of sexual partners. The high prevalence of LAV/HTLV-III seropositivity in an area where overt AIDS (acquired immune deficiency syndrome) is still relatively uncommon suggests that public health measures to prevent acquisition and transmission of LAV/HTLV-III should be a high priority even in areas with low incidences of AIDS.

Study Objective: To analyze the relation between human immunodeficiency virus (HIV) infection and the antibody response to plasma-derived hepatitis B vaccine., Design: Open-label longitudinal cohort study; blinded laboratory studies., Setting: University-affiliated municipal hospital., Patients: Homosexually active men with negative assays for hepatitis B surface antigen (HBsAg), hepatitis B core antigen, and antibody to HBsAg; recruited in a sexually transmitted disease clinic or referred from community practitioners., Interventions: Immunization with 20 micrograms of plasma-derived hepatitis B virus vaccine intramuscularly, repeated after 1 and 6 months; standardized evaluation at entry and at 1, 2, 6, and 7 months., Measurements and Main Results: Low antibody response or nonresponse to vaccination occurred in 7 of 16 HIV-seropositive patients, compared with 6 of 68 HIV-seronegative patients (P = 0.002). Median levels of antibody to HBsAg 7 months after the first vaccine dose were 205.3 sample ratio units for HIV-seronegative patients and 15.5 sample ratio units for HIV-seropositive patients. By multivariate analysis, vaccine response was associated with HIV antibody status and not with cytomegalovirus infection, lymphocyte subset results, or impaired cutaneous delayed hypersensitivity., Conclusions: Infection with HIV is associated with suboptimal antibody response to plasma-derived hepatitis B virus vaccine. Determination of antibody levels after vaccination in HIV-seropositive patients may be warranted.

To investigate the relationships among cytomegalovirus infection, sexual behavior, human immunodeficiency virus (HIV) seropositivity, and indexes of cellular immunity, 180 homosexual men and 26 heterosexual men were studied. Among the homosexual men, cytomegalovirus seropositivity was associated with increased T8 lymphocyte counts (p less than 0.001) and reduced T4/T8 ratios (p = 0.006); these results were independent of HIV infection. Cytomegalovirus seropositivity was also associated with increasing age, numbers of sexual partners, and the practice of anal-receptive intercourse. At the first visit, cytomegalovirus was isolated from none of 13 cytomegalovirus-seropositive heterosexual subjects, compared with 62 (36 percent) of 171 seropositive homosexual men (p less than 0.005). Viral isolation was most common from semen. Among 32 cytomegalovirus-seropositive homosexual subjects from whom culture specimens were obtained more than four times over 10 to 30 months, 72 percent of the specimens were culture-positive. The mean duration of cytomegalovirus excretion in semen was 22 months, and in urine, the duration was nine months. Cytomegalovirus excretion was associated with younger age and reduced lymphocyte proliferation in response to cytomegalovirus, but not with antibody to HIV. Cytomegalovirus infection is sexually transmitted among homosexual men, perhaps by rectal intercourse, and is associated with alterations in T lymphocyte subsets. Most seropositive homosexual men excrete cytomegalovirus intermittently, primarily in the semen.

To assess the epidemiology and natural history of persistent generalized lymphadenopathy (PGL) and subclinical immunodeficiency in relation to serologic evidence of lymphadenopathy-associated virus/human T-lymphotropic virus type III (LAV/HTLV-III) infection, 109 homosexual men with PGL, 47 homosexual men without lymphadenopathy who attended a sexually transmitted disease (STD) clinic, 25 homosexual male university students, and 26 heterosexual men who attended the STD clinic were studied. In 1982-1983 antibody to LAV/HTLV-III was present in 97%, 35%, 21%, and 4% of the four groups, respectively (P less than .001). Subclinical immunodeficiency was more closely associated with LAV/HTLV-III seropositivity than with lymphadenopathy. Cohorts of 78 homosexual subjects with PGL, 35 homosexual subjects from STD clinic, and 15 homosexual university students were followed for median periods of 13.5, 20, and 14.5 months, respectively. The seroconversion rate was 23% per year among seronegative subjects, and 4% of seropositive subjects developed overt acquired immunodeficiency syndrome (AIDS). Among seronegative subjects, there was significant improvement in T4:T8 ratios (P = .001), whereas most seropositive subjects continued to have subnormal total counts of T4 lymphocytes and low T4:T8 ratios. Some cases of subclinical cellular immunodeficiency apparently are unrelated to LAV/HTLV-III infection, and the presence of antibody to this virus is associated with an unfavorable immunologic prognosis.

Single-dose ceftriaxone, 125 mg given intramuscularly, was compared with spectinomycin 2.0 g given intramuscularly in the treatment of women with uncomplicated gonorrhea. Cervical or anorectal gonococcal infection was eradicated in 54 (98 percent) of 55 women treated with ceftriaxone and 22 (96 percent) of 23 treated with spectinomycin. Cure rates for pharyngeal gonococcal infections were nine of 10 for ceftriaxone and four of eight for spectinomycin (p = 0.18). Neither agent eradicated concurrent Chlamydia trachomatis infection. The geometric mean minimal inhibitory concentration for ceftriaxone was 0.0038 microgram/ml for 65 pretreatment cervical isolates of beta-lactamase-negative Neisseria gonorrhoeae and all isolates were inhibited by 0.063 microgram/ml. Neither drug caused perceptible toxicity, but patient acceptance was better for ceftriaxone than for spectinomycin. A single 125 mg dose of ceftriaxone is an excellent regimen in the treatment of uncomplicated gonorrhea in women.