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Biomedical subjects

R Detels

Publications and source records attributed to R Detels.

At least 145 records · Page 8Linked to original sources
PubMed1990

A simple method for improved assay demonstrates that HIV p24 antigen is present as immune complexes in most sera from HIV-infected individuals.

Improved detection and quantitation of p24 antigen of the human immunodeficiency virus (HIV) in sera was obtained by pH 2.5-3.0 pretreatment of samples before using a standard HIV p24 antigen ELISA. Pretreatment dissociated immune complexes and denatured antibodies with little or no compromise of p24 antigen immunoreactivity. For 652 HIV antibody-positive sera, direct comparison of the pretreatment with the conventional assay demonstrated substantial increase in both antigen positivity (50.6% vs. 12.4%) and in the level of p24 antigen in sera. Serum HIV antigen is mainly in the form of immune complexes in most individuals at all stages of HIV infection. Longitudinal study of 1 year (three measurements) on 29 seroconverters demonstrated two main patterns of p24 antigen expression in sera: 34.5% of infected individuals never express any form of detectable HIV antigen and 58.6% persistently demonstrate serum p24 antigen, usually in complex with antibody. Only 6.9% show episodic p24 antigen positivity.

Antigen-Antibody Complex↗
PubMed1990

Seroprevalence of human T cell leukemia viruses in selected populations of homosexual men.

This study sought to define the seroprevalence of human T cell leukemia virus (HTLV) types I and II in selected populations of homosexual men. Serum specimens were screened for antibodies to HTLV and to human immunodeficiency virus (HIV) by enzyme immunoassay; successive testing of specimens with positive results was done by Western blotting and radioimmunoprecipitation assay (RIPA) and then by polymerase chain reaction (PCR) assay on available peripheral blood mononuclear cells (PBMC). Of 1290 specimens, only 4 had antibodies against HTLV confirmed by RIPA. PCR analysis of DNA from PBMC from two subjects showed one to be HTLV-I and the other to be HTLV-II; both men also had HIV antibodies. These results demonstrate a lower seroprevalence rate for HTLV than some previous studies and emphasize the need for specific confirmatory tests.

Blotting, Western↗
PubMed1990

Serum beta 2-microglobulin level increases in HIV infection: relation to seroconversion, CD4 T-cell fall and prognosis.

Beta 2-microglobulin (beta 2-M), a marker that is increased in serum during immune activation, was investigated during the course of HIV infection. beta 2-M rose promptly in the first phase of HIV infection in people who were participating in a longitudinal study where serum samples and lymphocyte subset data were obtained at 6-monthly intervals. A rise in beta 2-M level in the first seropositive sample was seen in 93% of 50 HIV seroconverters, and those with high (or low) levels of beta 2-M at the end of year 1 tend to remain high (or low) in the ensuing years. Eighty-three per cent of seroconverters experienced a fall in CD4 T cells in the first year. The magnitude of the CD4 T-cell decline, however, did not correlate with the rise in beta 2-M in specific individuals in the first year. Nevertheless, 2-3 years after seroconversion, the initially increased beta 2-M levels did correlate inversely with the (reduced) level of CD4 T cells (P less than 0.001). Thus, the pattern of disease reflected by beta 2-M level is established in the first year of infection and persists through the following 2 years. beta 2-M levels were found to correlate with rate of CD4 T-cell fall in individuals with established HIV infection. Three groups of HIV-seropositive people with similar CD4 T-cell numbers at the first measurements (about 600-800 x 10(6)/l) but different rates of CD4 T-cell fall over the following 2 years were evaluated by beta 2-M levels. The group with stable CD4 T-cell numbers showed a significantly lower level of beta 2-M than the groups with moderately or rapidly declining CD4 T-cell numbers. Increases in beta 2-M levels during the 2 years of observation were found in people exhibiting a rapid decline in CD4 T cells (about 200 cells/year). The level of beta 2-M appears to be an indicator of HIV activity and of the rate of CD4 T-cell fall.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

HIV-1, HIV-2, and HTLV-I infection in high-risk groups in Brazil.

We conducted a serologic survey for antibodies to human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and human T-cell lymphotropic virus Type I (HTLV-I) in 704 Brazilians with the acquired immunodeficiency syndrome (AIDS) or at risk for it. The study population included 70 homosexual men (11 of whom were prostitutes), 58 bisexual men (19 of whom were prostitutes), 101 female prostitutes from three socioeconomic groups, 13 wives of men with hemophilia who were seropositive for HIV-1 antibodies, and 47 blood donors with positive Venereal Disease Research Laboratory tests for syphilis, all from Rio de Janeiro; 86 female prostitutes from two rural towns in Minas Gerais; 133 patients with AIDS from São Paulo; and 196 men with bleeding disorders who were seropositive for HIV-1 antibodies on enzyme-linked immunosorbent assay, from São Paulo and Rio de Janeiro. The prevalence of HIV-1 infection was highest in the homosexual male prostitutes (45 percent), the wives of patients with hemophilia (38 percent), the bisexual men (28 percent), the homosexual men who were not prostitutes (19 percent), and the female prostitutes from the lower class (9 percent). Combined HIV-1 and HIV-2 infection was found in 3 percent of the patients with AIDS and in 1 percent of the homosexual men. The prevalence of HTLV-I infection ranged from 1 percent in rural female prostitutes to 13 percent in HIV-1-positive men with bleeding disorders in Rio de Janeiro. Combined HIV-1 and HTLV-I infection occurred in 1 to 11 percent of some male subgroups. We conclude that in Brazil HIV-1 infection is already well established among homosexuals, bisexuals, and lower-class female prostitutes, with bisexual men probably acting as a bridge between the heterosexual and homosexual communities, that HTLV-I infection is prevalent in groups at risk for AIDS, and that HIV-2 infection has already been introduced into the country.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Serum and effector-cell antibody-dependent cellular cytotoxicity (ADCC) activity remains high during human immunodeficiency virus (HIV) disease progression.

The activity of both serum and effector cell antibody-dependent cellular cytotoxicity (ADCC) against human immunodeficiency virus (HIV-1, HIV) was assessed in HIV-infected individuals. The goal was to relate ADCC levels with the stage or progression of HIV disease. Serial serum samples, usually collected at 6-month intervals, from individuals at defined stages of HIV disease (seroconversion, the HIV-seropositive period before AIDS, and around the time of clinical AIDS diagnosis) were tested. HIV-coated CEM tumor cells were used as targets. Effector-cell ADCC activity was evaluated using fresh peripheral blood mononuclear cells (PBMC) from HIV-infected individuals at different stages of HIV disease. Samples were obtained from male homosexual participants in the Multicenter AIDS Cohort Study (MACS). In seroconverters, ADCC-inducing HIV-specific antibodies were detected at the time that the ELISA antibody test was first positive. Within several months, serum ADCC activity stabilized in each individual. In 29 HIV-seroprevalent individuals (HIV seropositive on their first visit), serum ADCC activity remained constant regardless of whether the individual's HIV disease was stable (high stable CD4; n = 9) or rapidly deteriorating (sharply declining CD4, n = 10; AIDS progressors, n = 10). With respect to effector-cell activity, PBMC from HIV-infected individuals with or without AIDS were capable of mediating ADCC with heterologous and usually with autologous sera. Although the level of NK cytotoxic activity and the level of antibody-armed effector cell activity have been reported to decline as disease progresses, our results support previous observations that ADCC effector-cell activity against antibody-coated targets does not decline in HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1989

T-cell subset alterations in HIV-infected homosexual men: NIAID Multicenter AIDS cohort study.

Immunologic changes in HIV-infected homosexual men without AIDS were studied using flow cytometry and monoclonal antibodies. A decline in CD4 cells occurred after anti-HIV antibodies detectable by ELISA developed. CD4 T-cell levels dropped to an average of 60% of their original level within 12-18 months after seroconversion. Subsequently, CD4 levels remained constant in most HIV seropositive men for several years. However, in men who developed AIDS, there was a rapid fall in the CD4 level during the 2 years prior to development of AIDS. Throughout the course of HIV disease, the total T-cell levels (CD3) remained constant, apparently due to CD8 lymphocytosis. The selective depletion by HIV infection of discrete functional subsets of CD4 cells was examined using 4B4, 2H4, HB-11, and Leu-8 monoclonal antibodies and dual color immunofluorescence. No selective depletion of CD4 subsets was noted using any of these reagents. However, selective activation of subsets of CD8 lymphocytes characterized disease progression. In particular, increases in the number of HLA-DR+, CD38+ (OKT10), and Leu-8- CD8 lymphocytes were associated with a fall in CD4 levels and development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Cross-sectional study of reverse transcriptase-inhibiting antibody as a marker of acquired immune deficiency syndrome.

A cross-sectional study of 128 individuals infected with human immunodeficiency virus type 1 (HIV-1) was conducted to determine the correlation of reverse transcriptase-inhibiting (RTI) antibody to clinical disease. Thirty-two individuals were studied in each of four clinical groups: asymptomatic individuals, those with persistent generalized lymphadenopathy, those with acquired immune deficiency syndrome (AIDS)-related complex, and those with AIDS. Our study showed that 78% of asymptomatic individuals, 53% of those with persistent generalized lymphadenopathy, 50% of those with AIDS-related complex, and only 25% of those with AIDS have RTI antibody. Concurrent measurement of measles antibody level was used as an indicator of the immune status of these individuals. Measles antibody did not decline in persons with clinical disease, but asymptomatic individuals had lower antibody titers, possibly due to hypergammaglobulinemia associated with advanced HIV infection. These results indicate that more HIV-infected asymptomatic individuals than symptomatic individuals have RTI antibody. This suggests either that the RTI antibody level decreases with the progression of disease in HIV infection or that symptomatic individuals do not produce RTI antibody. The presence or absence of RTI antibody can thus be used as a marker of advanced disease.

AIDS-Related Complex↗
PubMed1989

A case-control study of multiple sclerosis.

We conducted a study of 145 persons with multiple sclerosis who had been identified in a 1970 survey and 145 friend controls, to investigate whether the development of MS was associated with exposure to uncommon viruses or an older age at infection with 1 or more common viruses. The most striking finding was a strong positive association for history of infectious mononucleosis (IM), suggesting older age at exposure to Epstein-Barr virus, the most common etiologic agent of IM. We also found significant positive associations for number of different domiciles before adulthood and for visits outside the United States; both would be compatible with an increased likelihood among cases of exposures to uncommon viruses or to multiple strains of a common agent. Cases were younger at menarche, increasing the probability of viral exposure after puberty.

Adolescent↗
PubMed1989

CD4 percentage, CD4 number, and CD4:CD8 ratio in HIV infection: which to choose and how to use.

Data from a 3 year longitudinal study of CD4 levels in 813 untreated HIV-seropositive men are presented. Baseline CD4 levels were used to stratify the men for the severity of HIV disease at the outset of the study, and each man's CD4 levels and progression to AIDS were evaluated. These data can be used to advise patients who are HIV seropositive on the likelihood that they will deteriorate immunologically or progress to AIDS based on their own CD4 cell level obtained from laboratory evaluation. Graphs are presented here for 1, 2, and 3 years of follow-up. As expected, each individual's absolute CD4 lymphocyte number, CD4 lymphocyte percent, and CD4:CD8 ratio were strongly correlated, and were similar in their ability to predict the development of AIDS. In this sense, all three are useful markers for monitoring individuals with HIV infection, and for many clinical situations from a practical point of view there is little to choose between the markers. However, the CD4 percent has slightly greater prognostic significance and shows slightly less variability on repeated measurements. Because of this, the CD4 percent may be preferable to the CD4 absolute number for use in stratifying individuals who are candidates for antiviral or immunotherapy for HIV infection, and for monitoring patients in clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Designing interventions to prevent HIV-1 infection by promoting use of condoms and spermicides among intravenous drug abusers and their sexual partners.

This paper summarizes the results of a 2-day workshop to identify the most effective educational strategies to promote use of condoms and spermicides for preventing heterosexual transmission of HIV-1 virus from intravenous drug abusers (IVDA) to their steady, nonintravenous drug abusing (NIVDA) sexual partners. Representatives from health departments, drug abuse treatment centers, academic institutions, service organizations, and the community discussed issues relating to population characteristics, educational strategies and recruitment techniques. A consensus document that identifies the most effective recruitment and intervention strategies was developed. Recruitment issues include locations, recruitment targets, anticipated difficulties, and ethical considerations. The majority of workshop participants agreed that an intervention should target the couple (both IVDA and NIVDA). Intervention concerns encompass obtaining trust, maintaining participation, and identifying guidelines to maximize program impact.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Serum neopterin changes in HIV-infected subjects: indicator of significant pathology, CD4 T cell changes, and the development of AIDS.

Serum neopterin is a metabolite of dihydroneopterin triphosphate, which is produced from GTP during immune activation. A study was undertaken in homosexual male subjects followed at 6 month intervals for 3 or more years to determine the value of serum neopterin changes induced by HIV infection. The significance of serum neopterin levels in evaluating prognosis of HIV-infected individuals was also assessed. Serum neopterin was found to be a useful indicator of the presence of HIV infection. Stratification of 29 HIV seroconverters showed a strong inverse correlation between the serum neopterin rise and the blood CD4 T cell fall in the first year following HIV infection. Thus, a small increase in neopterin (less than 5 nmol/L) at the time of HIV seroconversion was associated with minimal CD4 T cell reduction and a large increase (greater than 12 nmol/L) was associated with a much greater CD4 T cell fall. Neopterin levels were markedly different (lower) in individuals with little or no CD4 T cell fall when compared with those with moderate or marked rates of T cell fall. This relationship between serum neopterin and the CD4 T cell level was further confirmed by an evaluation of both parameters in a group of 799 seropositive homosexual men. In this analysis, serum neopterin was shown to have a significant predictive value for the development of AIDS within 3 years. Furthermore, when serum neopterin and CD4 T cell measurements were considered together, the prognostic value of the combination was significantly greater than either alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Seroconversion, sexual activity, and condom use among 2915 HIV seronegative men followed for up to 2 years.

A cohort of 2915 HIV-1-seronegative men from the four centers of the Multicenter AIDS Cohort Study (MACS) was followed at 6 month intervals for 24 months to identify men who developed antibodies to HIV-1. Two hundred thirty-two men (8%) seroconverted. The highest attack rate was among men who reported practicing both receptive and insertive anal-genital intercourse. The attack rate among men who reported practicing receptive but not insertive intercourse was 3.6 times higher than among men practicing insertive intercourse although those practicing insertive only reported 38% more different partners. Only two men seroconverted who reported not practicing analgenital intercourse in the 12 month prior to the first antibody-positive visit. Because men were followed every 6 months, one of these men could have been infected within 6 months of the actual development of HIV-1 antibodies. The seroconversion rate was significantly lower among men who reported using condoms with all their partners. The results of this study (a) reaffirm that receptive anal-genital intercourse is the major route of infection among homosexual men of HIV-1, (b) suggest that there is a low risk of HIV-1 infection to the insertive partner in anal-genital intercourse, (c) suggest that infection may rarely occur through sexual activities other than anal-genital intercourse, (d) provide evidence that condoms as currently used by men in the MACS provide significant but not complete protection against HIV-1 infection, and (e) suggest that the number of men in the homosexual community engaging in high-risk behavior is declining.

Bisexuality↗
PubMed1988

Patterns of CD4+ cell changes after HIV-1 infection indicate the existence of a codeterminant of AIDS.

Successive interval slopes of CD4+ cells each constructed from levels at three consecutive 6 month visits were compared over 3 years of follow-up among 565 persistently HIV-1 antibody-positive, 326 persistently antibody-negative, and 51 seroconverting homosexual men who had at least 500 CD4+ cells/mm3 at baseline and completed the first three 6 month visits. "Change" was defined as a difference between two successive interval slopes. Sixty-two percent of seroconverters meeting these criteria experienced a shift in one or more of their successive CD4+ interval slopes, the majority (56%) from a level slope to a negative slope (decreasing numbers of CD4+ cells), a significantly greater proportion than that observed among seronegatives (30%, p less than 0.0001). Fifty-eight percent of the seropositives maintained level interval slopes over the 3 years of follow-up. The majority (59%) of those men experiencing a shift went from a level to a negative interval slope, a significantly greater proportion than observed among seronegatives (30%, p less than 0.0001). The observed patterns of change in interval slopes are consistent with the laboratory observation that CD4+ cells must be activated to replicate HIV-1. The use of the interval slope strategy provides a method to identify a temporal focal point at which to examine possible codeterminants that trigger the production of HIV-1 and the subsequent decline in CD4+ cells.

AIDS Serodiagnosis↗
PubMed1987

Early effects of HIV on CD4 lymphocytes in vivo.

Low circulating CD4 cell numbers and CD4 cell dysfunction are distinguishing features of HIV-mediated disease. The current study delineates the in vivo effects of HIV on distinct functional subsets of CD4 cells in homosexually active men who have been infected with HIV for different lengths of time, and examines the capacity of lymphocytes from these men to proliferate in vitro in response to soluble antigen. Although peripherial blood mononuclear cells from most acquired immune deficiency syndrome (AIDS) patients did not proliferate in response to either tetanus toxoid or Candida albicans, cells from most HIV seropositive men without AIDS, many of whom had been infected for more than 18 mo, responded normally to both. Non-responsiveness in HIV-infected men without AIDS was a late event and was associated with longer duration of infection, lower CD4 cell numbers, and subsequent development of AIDS. A defect in this response was observed in only one of 19 HIV seropositive men whose CD4 levels were greater than 300/mm3, but in eight of 10 with levels less than 300/mm3. The defect could not be attributed to a selective depletion of defined CD4 subpopulations that respond to soluble antigen. Dual-color immunofluorescent flow cytometry indicated that 4B4+, 2H4-, and HB-11- CD4 cells were not lost at a faster rate than other CD4 subsets.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Risk factors for seroconversion to human immunodeficiency virus among male homosexuals. Results from the Multicenter AIDS Cohort Study.

2507 homosexual men who were seronegative for human immunodeficiency virus (HIV) at enrollment were followed for six months to elucidate risk factors for seroconversion to HIV. 95 (3.8%) seroconverted. Of men who did not engage in receptive anal intercourse within six months before baseline and in the six-month follow-up period, only 0.5% (3/646) seroconverted to HIV. By contrast, of men who engaged in receptive anal intercourse with two or more partners during each of these successive six-month intervals, 10.6% (58/548) seroconverted. No HIV seroconversions occurred in 220 homosexual men who did not practise receptive or insertive anal intercourse within twelve months before the follow-up visit. On multivariate analysis receptive anal intercourse was the only significant risk factor for seroconversion to HIV, the risk ratio increasing from 3-fold for one partner to 18-fold for five or more partners. Furthermore, data for the two successive six-month periods show that men who reduced or stopped the practice of receptive anal intercourse significantly lowered their risk of seroconversion to 3.2% and 1.8%, respectively. Receptive anal intercourse accounted for nearly all new HIV infections among the homosexual men enrolled in this study, and the hazards of this practice need to be emphasised in community educational projects.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Selective alterations in immunoregulatory lymphocyte subsets in early HIV (human T-lymphotropic virus type III/lymphadenopathy-associated virus) infection.

In order to characterize the effects of HIV (human T-lymphotropic virus type III/lymphadenopathy-associated virus) on the immune system, Leu8- and Leu8+ subsets of CD4 and CD8 cells were studied in seropositive homosexually active men without acquired immune deficiency syndrome (AIDS). Controls included both heterosexual men and HIV-seronegative homosexually active men. The decrease in CD4 levels, observed in HIV-seropositive men who were asymptomatic, as well as in those who had persistent generalized lymphadenopathy or constitutional symptoms of HIV infection, occurred proportionally in both the Leu8- and the Leu8+ CD4 subsets. This observation, that HIV infection does not selectively diminish either subset of CD4 cells, indicates that the selective loss of T cell-mediated functions which accompanies the development of AIDS is not related to preferential loss of the Leu8+ CD4 subset. Among CD8 cells, however, HIV infection resulted in a threefold elevation in the number of Leu8- CD8 cells, while the number of Leu8+ CD8 cells remained constant. The increase in Leu8- CD8 cells was present in recent seroconverters, persistently seropositive men, and patients with AIDS. We propose that the increase in Leu8- CD8 cells represents an HIV-specific cytotoxic T-cell response. These cells may operate by killing infected CD4 cells, thereby partially controlling viral infection while simultaneously contributing to the destruction of the immune system.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The Multicenter AIDS Cohort Study: rationale, organization, and selected characteristics of the participants.

The Multicenter AIDS Cohort Study was designed to elucidate the natural history of the infection causing acquired immunodeficiency syndrome (AIDS), identify risk factors for occurrence and clinical expression of the infection, and establish a repository of biologic specimens for future study. A variety of recruitment techniques, including special assurance of confidentiality, were used to enroll participants. Nearly 5,000 homosexual men volunteered for semiannual interview, physical examination, and laboratory testing in four metropolitan areas. A significant majority of these men in each center (69-83%) reported having 50 or more lifetime sexual partners, and over 80% had engaged in receptive anal intercourse with at least some of their partners in the previous two years. By the time of the participants' initial evaluation (April 1984-April 1985), infection with the human immunodeficiency virus (HIV) had occurred in higher proportions of men in Los Angeles (51%) and Chicago (43%) than in Baltimore/Washington, DC (31%) and Pittsburgh (21%), presumably as a result of the higher number of partners and proportion with whom these men had engaged in high-risk practices (e.g., receptive anal intercourse). Follow-up evaluations are underway in this comprehensive longitudinal investigation of HIV infection.

Acquired Immunodeficiency Syndrome↗