High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects.

BACKGROUND: In clinical trials, canarypox ALVAC-human immunodeficiency virus (HIV) vaccines have been shown to elicit human HIV-specific cytotoxic T lymphocyte (CTL) responses in some but not all healthy uninfected adults.Methods. A clinical trial was conducted to examine whether the vaccine vCP1452 would elicit a greater HIV-specific CTL response when given at a dose of 10(8.0) TCID50 (60 participants) than when given at the regular dose, 10(7.26) TCID50 (40 participants); as a control, a placebo vaccine preparation also was administered (10 participants). RESULTS: Two weeks after the last vaccination in a series, HIV-specific CTL responses were not significantly different when measured by either chromium-release assay (8% and 16% in the high- and regular-dose recipients, respectively) or interferon- gamma ELISpot assay (8% and 15% in the high- and regular-dose recipients, respectively); moreover, recipients of the higher dose had greater local and systemic reactions (P<.001). CONCLUSIONS: High reactogenicity associated with an increased dose of vCP1452 negates the need for further evaluation of this strategy to boost the frequency of HIV-specific CTL response in seronegative human subjects. Development of highly immunogenic canarypox vectors requires further work to optimize vector and insert design, as well as novel ways to increase dosage and to reduce reactogenicity.

Non-injection substance use correlates with risky sex among men having sex with men: data from HIVNET.

Associations between substance use and sexual behavior were examined among 3220 seronegative men who have sex with men (MSM) in a HIV vaccine preparedness study. Relationships between current and past substance use and current sexual risk were evaluated using crude odds ratios and logistic regression to adjust for confounding variables. Heroin and injection drug use were uncommon (< 2%). Substances most often used were alcohol (89%), marijuana (49%), nitrite inhalants (29%), amphetamines or similarly acting stimulants (21%), cocaine 14% and hallucinogens (14%). Increased adjusted odds for unprotected sex were significantly associated with current heavy alcohol use (OR 1.66; CI 1.18, 2.33), past alcohol problems (OR 1.25; CI 1.05, 1.48), and current drug use (OR 1.26; CI 1.08, 1.48). When associations with specific drugs and nitrite inhalants were examined separately, current use of cocaine and other stimulants (OR 1.25; CI 1.01, 1.55), hallucinogens (OR 1.40; CI 1.10, 1.77), and nitrite inhalants (some (OR 1.61; CI 1.35, 1.92); heavy (OR 2.18; CI 1.48, 3.20)), were independently associated with unprotected sex. Those with past drug use or past heavy alcohol use but not currently using demonstrated no increase in sexual risk, suggesting an important role for substance-focused interventions in risk reduction efforts among MSM.

Cellular and humoral factors in colostrum of HIV infected and uninfected lactating mothers.

OBJECTIVE: To compare the cellular and humoral factors in colostrum from HIV infected and uninfected lactating mothers. DESIGN: Cross sectional study. SETTING: Maternity Ward. METHODS: Colostrum was collected from 130 mothers (62 HIV seropositives and 68 HIV seronegatives). These colostrum samples were tested for total cell count, cell viability, differential count, phagocytic activity of macrophages, 'T' cell counts, IgA, IgM and IgG levels. RESULTS: There was a statistically significant decrease in the phagocytosis and 'T' cell number (p <0.001) and in the IgA and IgG levels (p<0. 05) in the colostrum obtained from HIV seropositive mothers as compared to HIV seronegative ones. CONCLUSION: Some of the cellular and humoral factors are reduced in colostrum samples obtained from HIV seropositives as compared to normals.

Massage therapy is associated with enhancement of the immune system's cytotoxic capacity.

Twenty-nine gay men (20 HIV+, 9 HIV-) received daily massages for one month. A subset of 11 of the HIV+ subjects served as a within subject control group (one month with and without massages). Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number, Natural Killer Cell Cytotoxicity, soluble CD8, and the cytotoxic subset of CD8 cells. There were no changes in HIV disease progression markers (CD4, CD4/CD8 ratio, Beta-2 microglobulin, neopterin). Major neuroendocrine findings, measured via 24 hour urines included a significant decrease in cortisol, and nonsignificant trends toward decrease of catecholamines. There were also significant decreases in anxiety and increases in relaxation which were significantly correlated with increases in NK cell number. Thus, there appears to be an increase in cytotoxic capacity associated with massage. Implications for HIV+ men as those with other illnesses, particularly cancer, are discussed.

Elevated IgE level in relationship to nutritional status and immune parameters in early human immunodeficiency virus-1 disease.

Elevation of IgE has been associated with T-cell dysregulation and with the occurrence of opportunistic infections in patients with acquired immunodeficiency syndrome. The precise cause of IgE overproduction during the early stages of human immunodeficiency virus (HIV)-1 disease, however, has not been established. In light of reports demonstrating that IgE production may be affected by vitamin E levels in an animal model, we evaluated nutritional status in relationship to plasma IgE levels and immune parameters in 100 asymptomatic HIV-1-seropositive and 42 HIV-1-seronegative homosexual men. Approximately 18% of the HIV-1-seropositive population demonstrated biochemical evidence of plasma vitamin E deficiency (< 5 micrograms/ml). Subsequent analysis of available samples indicated a dramatic elevation of IgE levels (308 +/- 112 IU/ml) in vitamin E-deficient seropositive subjects (n = 9) as compared with age and CD4-matched HIV-1-seropositive persons with adequate vitamin E levels (n = 16, 118.1 +/- 41.1 IU/ml) and significantly lower levels (59.5 +/- 15.7 IU/ml) in HIV-1-seronegative men (n = 20, p = 0.01). This effect, which was independent of CD4 cell count, did not appear to be influenced by atopic or gastrointestinal parasitic disease. The low plasma vitamin E levels were related at least in part to dietary intake (r = 0.552, p = 0.01), suggesting that supplementation may be warranted in HIV-1-infected persons in whom vitamin E deficiency develops. Analysis of covariance revealed a strong relationship between IgE levels and CD8 cell counts (p < 0.006), and between IgE level and vitamin E deficiency (p < 0.039).(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of natural killer cell activity in human immunodeficiency virus-infected subjects by in vitro treatment with biologic response modifier OK-432.

A decrease in natural killer (NK) cell function has been related to the progression of human immunodeficiency virus (HIV) infection. In the present study, we assessed the ability of a streptococcus-derived biologic response modifier, OK-432, to augment NK lysis of uninfected K562 and U937 cells and HIV-infected U937 cells by peripheral blood mononuclear cells (PBMC) from HIV-seropositive homosexual men. Optimal two- to fourfold increases in lysis of the three targets were observed after pretreatment of PBMC from HIV-negative subjects for 4 h with 2 micrograms of OK-432 per ml. This effect was related primarily to gamma interferon (IFN-gamma) production induced by OK-432 and was not linked to production of tumor necrosis factors alpha and beta or to monocytes in the cultures. The enhancing effect of OK-432 on NK cell function was diminished but still evident in PBMC from subjects with relatively early-phase (< 3-year) HIV infection and high CD4+ cell counts and was lower in subjects with longer-term HIV infection (> 3 years), in association with reduced production of IFN-gamma. Augmentation of NK cell activity in HIV-infected men by OK-432 was comparable to that induced by treatment of cells with 1,000 U of IFN-alpha or interleukin 2 per ml. The data suggest that the NK cell-enhancing effects of OK-432 are at least in part mediated by IFN-gamma and that OK-432 may be effective in treatment of patients with early-phase HIV infection.

Psychological distress and natural killer cells in gay men with and without HIV infection.

OBJECTIVE: The variability of the decline in immune function among those infected by HIV raises the possibility that psychological factors might help to explain the differences. Since studies of other populations have shown natural killer (NK) cells to be affected by psychiatric conditions, the authors examined this relationship in the context of HIV infection, expecting to find fewer NK cells to be associated with greater psychological distress. METHOD: Forty-six HIV-negative and 74 HIV-positive gay men who were participating in a longitudinal study had NK cells enumerations performed (by staining for CD56) 36 months after entry into the study. Comparisons were made between HIV-negative, HIV-positive asymptomatic, and HIV-positive symptomatic men by using a variety of clinician-rated and self-report measures of psychological function and absolute NK cell number. RESULTS: HIV-negative men had more NK cells than the groups of HIV-positive men. The groups' measures of psychological distress did not differ in any clinically meaningful ways. In general, the presence of DSM-III-R diagnoses and the measures of distress did not relate to NK cell number. CONCLUSIONS: NK cell number is not related to measures of psychological distress in these gay men with and without HIV infection.