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R Detels

Publications and source records attributed to R Detels.

At least 109 records · Page 6Linked to original sources
PubMed1995

Virus burden in long-term survivors of human immunodeficiency virus (HIV) infection is a determinant of anti-HIV CD8+ lymphocyte activity.

Persons infected with human immunodeficiency virus (HIV) for > 8 years were studied to delineate virologic and immunologic attributes of long-term survival. Whereas those with 300-700 CD4+ cells/microL often had circulating cytotoxic T lymphocytes (CTL) against HIV antigens, those with > 1000 CD4+ cells/microL did not. The subjects with > 1000 CD4+ cells/microL had low virus burden, low levels of Gag-specific CTL precursors, and minimal CD8+ cell activation. Overall, elevated levels of CD8+ cells, CD38 antigen expression on CD8+ cells, and anti-HIV functions were correlated with increased virus burden, provirus load, and HIV plasma RNA levels. A factor that suppressed HIV replication was spontaneously secreted from CD8+ cells of most subjects but not from those with high CD4+ cell counts. CD8+ cell activities, therefore, may reflect chronic viral stimulation of the immune system. Long-term survivors with high levels of CD4+ cells maintained control of viral replication but lacked the CD8+ cell activities.

ADP-ribosyl Cyclase↗
PubMed1994

The effect of the interaction of acyclovir with zidovudine on progression to AIDS and survival. Analysis of data in the Multicenter AIDS Cohort Study.

OBJECTIVE: To examine the effect of acyclovir use on disease progression and survival in human immunodeficiency virus (HIV)-seropositive persons treated with zidovudine. SETTING: Four university-based or -affiliated clinics. DESIGN: Prospective cohort study of homosexual and bisexual men with semi-annual follow-up. Intent-to-treat Cox models were fit to determine the relation between the use of acyclovir (modeled as a time-dependent covariate) and disease progression, controlling for baseline and time-dependent clinical and laboratory prognostic variables. The acquired immunodeficiency syndrome (AIDS)-free duration and survival time were calculated from the first use of zidovudine. Analysis included study visits 7 to 17 (from 1987 to 1992). PATIENTS: 786 HIV-seropositive participants in the Multicenter AIDS Cohort Study who began zidovudine therapy before a clinical diagnosis of AIDS; of these, 515 subsequently received acyclovir. Participants were asked at each visit whether they had "used any medication for health reasons not related to AIDS or if they had taken any medication to help fight AIDS or the HIV virus"; 488 patients indicated acyclovir use under either or both questions, and 242 patients indicated only the latter use. RESULTS: The use of acyclovir for any indication was not associated with an effect on progression to AIDS but was associated with a 26% decrease in the risk for death (relative hazard, 0.74; P = 0.07). The use of acyclovir for HIV infection was also not associated with an effect on progression to AIDS but was associated with a 36% decrease in the risk for death (relative hazard, 0.64; P = 0.01). To further investigate these findings, we examined dose, constancy, and timing of acyclovir use. The median daily dose of acyclovir used for HIV infection was between 600 and 800 mg. No apparent dose effect on survival was found. Longer uninterrupted use of acyclovir for any indication was associated with an 18% decrease in the risk for death for three or more consecutive visits (relative hazard, 0.82; P = 0.23), a 28% decrease for four or more consecutive visits (relative hazard, 0.72; P = 0.09), and a 7% decrease per visit based on the cumulative number of visits while the patient received acyclovir (relative hazard, 0.93 per visit increase; P = 0.03). Use of acyclovir for any indication and use of acyclovir for HIV infection were each associated with a 44% decreased probability of death if the drug was used after AIDS developed (P = 0.007 and P = 0.005, respectively) but not before. To further investigate the prolongation of survival, two landmark analyses were done. The first analysis began at a landmark of 1 year after initiation of zidovudine therapy and compared three groups of patients: those who used acyclovir at or before this landmark, those who had never started acyclovir or started the drug after the landmark, and those who had never used acyclovir. The 90% survival times were 1325, 1059, and 982 days, respectively. The second analysis began at a landmark of developing either a CD4 count less than 50 cells/microL or clinical AIDS. The 90% survival times for the three groups were 398, 261, and 176 days, respectively. CONCLUSIONS: Our analysis suggests that consistent use of acyclovir at a dose sufficient to suppress herpetic recurrences (that is, 600 to 800 mg/d) has a clinically significant effect on prolonging survival in a well-characterized cohort with extensive previous exposure to herpesvirus infections. Further clinical investigation of low-dose acyclovir with concomitant antiretroviral therapy is warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Persistent cytomegalovirus infection of semen increases risk of AIDS.

To evaluate if persistent cytomegalovirus (CMV) infection of semen in human immunodeficiency virus type 1 (HIV-1) antibody-positive men increases AIDS risk, serial cultures for CMV every 3-6 months were attempted four or more times from 164 men followed 3 years. CMV was never isolated from 58 men, in 1 or 2 samples from 54 (intermittently positive), and in > or = 3 samples from 52 (persistently positive). The Cox model was used to estimate relative hazards while controlling for CD4 cell number. The relative hazard was 2.9 for those intermittently and 4.0 for those persistently positive (P < .001). No Kaposi's sarcoma occurred in culture-negative men, 3 cases (5.6%) in intermittently positive men, and 4 cases (7.7%) in persistently positive men (P < .04). Persistent CMV in semen increases the hazard of AIDS in HIV-1 antibody-positive men, possibly by activating CD4 cells to produce HIV-1. Thus, control of CMV in HIV-1-infected persons may slow progression to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

A longitudinal study of cytomegalovirus infection in human immunodeficiency virus type 1-seropositive homosexual men: molecular epidemiology and association with disease progression.

Cytomegalovirus (CMV) isolates from 234 asymptomatic human immunodeficiency type 1 (HIV-1)-positive men were analyzed for molecular relatedness using junctional hybridization. Of isolates shed simultaneously at two or more body sites, 36% from 22 men were different. Of 180 isolates collected from 67 men over 15 months, different strains were isolated serially from 27 men (40%), most from semen. After follow-up of 58 months (mean), the relative hazard of HIV infection progressing to AIDS was 1.8 (95% confidence interval [CI], 0.9-3.7) for men shedding the same strain of CMV and 3.0 (95% CI, 1.4-6.1) for men shedding different strains compared with men not shedding CMV in semen. The prevalence of CMV-specific IgM was higher in men shedding different versus same CMV strains (32% vs. 18%; P = .244). Thus, presence of multiple CMV strains in HIV-1-positive homosexual men is associated with progression to AIDS, possibly via activation of HIV-1-infected CD4 cells.

Cohort Studies↗
PubMed1994

Communicable disease control in England; recommendations from an American.

The problems associated with the Wakefield salmonella and the Stafford Legionnaires' disease outbreaks and the recommendations of the Acheson Committee formed in response led to the creation of the position of Consultant in Communicable Disease Control (CCDC) within the District Health Authorities. The reality of the position as implemented differs from that envisaged by the Acheson Committee and has resulted in ambiguities about the role of the CsCDC, the source of their support, and the range of their responsibilities. This paper, by an American invited to review the position, outlines the history of the position, the current status of CsCDC, and the barriers to effective performance of the position. It ends with a series of recommendations for improving disease control within England by solidifying the position, establishing its role in disease control within the National Health Service and recommending an educational/training pathway to attract and prepare physicians for the position.

Communicable Disease Control↗
PubMed1994

The UCLA population studies of chronic obstructive respiratory disease: XI. Impact of air pollution and smoking on annual change in forced expiratory volume in one second.

We assessed the relative impact of residential exposure to community air pollution and habitual cigarette smoking on lung function by comparing the annualized rate of change in forced expiratory volume in 1 s (FEV1) in current, former, and never-smokers 25 to 59 yr of age residing in three demographically similar areas of the Southern California air basin who had been chronically exposed to (1) moderate levels of photochemical oxidants and very low levels of other pollutants (Lancaster); (2) very high levels of photochemical oxidants, sulfates, and particulate matter (Glendora); and (3) high levels of sulfates, oxides of nitrogen, and probably hydrocarbons (Long Beach), together with moderate levels of sulfur dioxide. Of the 621 to 763 nonsmokers, 317 to 479 former smokers and 472 to 691 continuing smokers residing in the three areas who were studied initially, 53 to 64, 49 to 59, and 43 to 54%, respectively, were retested. For male residents, area of residence and smoking category each had highly significant effects on FEV1 decline (two-way ANCOVA; p < 0.001) without significant interaction (p > 0.4). After adjustment for baseline FEV1, age, height, and a history of allergy, the mean decline in FEV1 attributable to living in Long Beach compared with living in Lancaster was 23.6 ml/yr, which was 71% of the rate of decline in FEV1 (33.3 ml/yr), attributable to smoking > 1 pack of cigarettes per day. For female residents, a significant interaction was noted between area and smoking (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Phenotypically defined memory CD4+ cells are not selectively decreased in chronic HIV disease.

Simultaneous measurements of phenotypically defined memory CD4+ cells and in vitro proliferation to three recall antigens (Ags; tetanus toxoid, influenza, and Candida albicans) were performed in 53 HIV-seropositive subjects and 39 HIV-seronegative controls. The results indicate that the low proliferative responses to recall Ags of those who were HIV infected could be partly, but not fully, explained by a decrease of phenotypically defined memory CD4+ cells. This is, to our knowledge, the first report of experiments that simultaneously measured memory CD4+ cell numbers and function and then examined whether the low responses observed in seropositive subjects could be explained by low numbers of phenotypically defined memory CD4+ cells. A central finding of the study, which argues against prevailing dogma, was that within the CD4+ lymphocyte population, the proportion of cells displaying the memory phenotype was not selectively decreased in HIV-seropositive subjects as compared with the proportion of these cells in seronegative homosexual controls. An entirely new finding of the study was that AIDS patients, many of whom were unresponsive to all three recall Ags tested, actually had a significant increase in the proportion of CD4+ cells with the memory phenotype, and this fraction approached 100% in subjects with CD4+ cell numbers that were near zero. A final observation of the study, possible because some patients were on zidovudine (ZDV), was that there was no evidence that ZDV treatment led to an increased proliferative response to recall Ags in vivo. An in vitro study also found no effect of ZDV, dideoxycytidine (ddC), or azido-dideoxyuridine (AZU) on proliferative responses to recall Ags.

CD4-Positive T-Lymphocytes↗
PubMed1994

Thrush and fever as measures of immunocompetence in HIV-1-infected men.

The occurrence of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus type 1 (HIV-1)-infected individuals with high CD4+ counts indicates poor immunologic function. Thrush and persistent fever, easily recognized clinically, are potential measures of immunocompetence. This analysis establishes the complex interactions of CD4+ count, thrush, and persistent fever to predict the occurrence of PCP. Analyses used 20,632 person visits from 2,568 HIV-1-seropositive homosexual or bisexual men participating in the Multicenter AIDS Cohort Study (MACS). Comprehensive examinations were conducted semiannually, while occurrences of PCP were assessed continuously. The occurrence of thrush and fever increase in frequency as CD4+ levels decrease. The relative hazard of PCP in the presence of thrush compared with the absence of thrush rises (p < 0.05) from 1 for the lowest CD4+ category to approximately 5 in the highest categories. The relative hazard of PCP in the presence of fever compared with the absence of fever is above one (p < 0.05) in all CD4+ categories. No cases of PCP occurred in individuals on PCP prophylaxis with CD4+ counts > 200/mm3. These results suggest that HIV-1-related symptoms provide a measure of failing immune function that is not reflected by enumeration of CD4+ lymphocytes alone and support the United States Public Health Service recommendation that symptomatic individuals with CD4+ counts > 200/mm3 should be considered for PCP prophylaxis.

Bisexuality↗
PubMed1994

Resistance to HIV-1 infection. Multicenter AIDS Cohort Study.

Men from the Multicenter AIDS Cohort Study were classified as "susceptible" and "resistant" to HIV infection. Resistant men were still HIV antibody negative in 1993 and were estimated to have had > 45 different anal intercourse partners (median, 92; range, 46-504) in the 2.5 years before visit 2 (1985). Susceptible men were seroconverters who were estimated to have had < 13 different anal partners (median, 4; range, 0-12). Leukocyte groups were compared between the two groups of men. Values were excluded for 12 months before the first antibody-positive visit in the susceptible men. White blood cells, polymorphonuclear neutrophils, total lymphocyte count, CD8+ percentage and number, and CD3+ and CD4+ number were higher in the resistant men. Logistic regression analyses were used to develop 50 bivariate models. Higher levels of neutrophils and CD8+ cells were included in four of the six best-fitting bivariate models, suggesting that each is associated with resistance to HIV-1 infection. These results support the hypothesis that CD8+ cells may modulate the outcome of HIV-1 exposure.

CD8-Positive T-Lymphocytes↗
PubMed1993

Clinical manifestations of AIDS in the era of pneumocystis prophylaxis. Multicenter AIDS Cohort Study.

BACKGROUND: Among patients infected with human immunodeficiency virus type 1 (HIV-1), early and widespread use of prophylactic regimens against Pneumocystis carinii is changing the pattern of illnesses related to the acquired immunodeficiency syndrome (AIDS). METHODS: We conducted a subcohort analysis of 844 men with AIDS (87 percent of whom have since died) from a prospectively followed cohort of 2592 HIV-1-infected homosexual men. RESULTS: A total of 138 men received prophylaxis before the diagnosis of AIDS, but 39 (28 percent) nevertheless had P. carinii pneumonia at some time. Only four illnesses occurred more frequently in men who received P. carinii prophylaxis before the onset of AIDS: Mycobacterium avium complex disease, which developed in 33.4 percent, as compared with 17.3 percent of the 706 men who did not receive early prophylaxis; wasting syndrome (18.4 percent vs. 6.4 percent); cytomegalovirus disease (44.9 percent vs. 24.8 percent); and esophageal candidiasis (21.3 percent vs. 12.8 percent). Collectively, these four diseases accounted for the initial AIDS-related illness in 42.7 percent of those who received prophylaxis before the onset of AIDS, as compared with 10.7 percent of those who did not. During the three six-month periods before the diagnosis of AIDS (0 to 6, > 6 to 12, and > 12 to 18 months), the geometric mean CD4+ cell counts were 48, 87, and 147 per cubic millimeter, respectively, in men who received prophylaxis against P. carinii, as compared with 118, 211, and 279 per cubic millimeter in those who did not. CONCLUSIONS: M. avium complex disease, esophageal candidiasis, wasting syndrome, and cytomegalovirus disease are more common in HIV-infected patients who have received prophylaxis against P. carinii than in those who have not. Prophylaxis may delay the first AIDS illness for 6 to 12 months.

AIDS-Related Opportunistic Infections↗
PubMed1993

Racial and ethnic differences in human immunodeficiency virus type 1 (HIV-1) seroprevalence among homosexual and bisexual men. The Multicenter AIDS Cohort Study.

To determine whether the excess prevalence of human immunodeficiency virus type 1 (HIV-1) infection in US black and Hispanic homosexual men relative to white men can be explained by differences in sociodemographic factors, history of sexually transmitted diseases, or sexual and drug-use behaviors, the authors conducted a cross-sectional analysis of baseline HIV-1 seroprevalence and HIV-1 risk factors among 4,475 non-Hispanic white, 234 Hispanic white, and 194 black homosexual men from four centers in the United States (Baltimore/Washington, DC, Pittsburgh, Chicago, and Los Angeles). HIV-1 seroprevalence was significantly higher in Hispanic men (50%; odds ratio (OR) = 1.83, 95% confidence interval (CI) 1.41-2.39) and black men (47%; OR = 1.62, 95% CI 1.21-2.16) compared with white men (35%). Both Hispanic and black men more frequently reported a history of sexually transmitted diseases. Overall, Hispanics had the highest risk profile and blacks the lowest risk profile with respect to certain high-risk sexual behaviors (e.g., receptive anal intercourse and use of anonymous sexual partners) and recreational drug use. After multivariate adjustment, black race remained a significant independent risk factor for HIV-1 seropositivity (OR = 1.60, 95% CI 1.13-2.26), but Hispanic ethnicity was no longer statistically significant (OR = 1.17, 95% CI 0.82-1.69). Most of the excess HIV-1 prevalent infection among Hispanics was explained by their predominant recruitment from Los Angeles--the study center with the highest HIV-1 seroprevalence--and their greater prevalence of a history of sexually transmitted diseases and certain high-risk sexual practices. By contrast, adjustment for these same risk behaviors failed to explain the observed black-white differences in HIV-1 seroprevalence, and further studies are needed to elucidate the reasons for these unexplained racial differences. HIV-1 educational programs for homosexual men should take into account the behavioral differences that exist between white and minority racial/ethnic groups.

Black or African American↗
PubMed1993

Trends in the incidence of outcomes defining acquired immunodeficiency syndrome (AIDS) in the Multicenter AIDS Cohort Study: 1985-1991.

Incidence of clinical outcomes defining acquired immunodeficiency syndrome (AIDS) may be expected to change as a consequence of progressive immunosuppression and use of chemoprophylaxis before the onset of AIDS. Using Poisson regression methods, we examined trends in the incidence of initial and secondary AIDS-defining illnesses from 1985 to 1991 among 2,627 homosexual men participating in the Multicenter AIDS Cohort Study who were seropositive for human immunodeficiency virus type 1. The incidence of Pneumocystis carinii pneumonia rose steeply until 1987 but has declined since then (p < 0.001), while the other AIDS-defining conditions have showed significant (p < or = 0.039) upward trends. Trends for Kaposi's sarcoma, lymphoma, neurologic disease, and cytomegalovirus/herpes simplex virus infections were explained by progressive immunosuppression, but residual downward and upward trends were present for P. carinii pneumonia and other opportunistic infections (bacterial, fungal, and protozoal infections and wasting syndrome). Despite selection bias, those receiving P. carinii pneumonia chemoprophylaxis showed a significantly lower incidence of P. carinii pneumonia (relative risk = 0.32, 95% confidence interval 0.16-0.63), and the time trends of P. carinii pneumonia were explained by progressive immunosuppression and use of prophylaxis. No significant effects on all other diagnoses were seen in those selected to receive antiretroviral therapy. Secondary diagnoses showed a strongly significant (p < 0.001) increase in non-P. carinii pneumonia and non-Kaposi's sarcoma among those with initial diagnoses of Kaposi's sarcoma. Overall, the trend observed in the incidence of other opportunistic infections underscores the need for developing and testing new strategies to curtail or delay the onset of these diseases.

AIDS-Related Opportunistic Infections↗
PubMed1993

Relationship of hepatitis B virus infection to human immunodeficiency virus type 1 infection.

The Multicenter AIDS Cohort Study (MACS) was designed to study the natural history of human immunodeficiency virus type 1 (HIV-1) infection, including the relationship between hepatitis B virus (HBV) and HIV-1 infection. In total, 4954 homosexual men were recruited from April 1984 through March 1985 and have been followed up thereafter every 6 months. Hepatitis B surface antigen and hepatitis B core antibody were tested for at the first visit by RIA or EIA; HIV-1 antibody testing was done at each visit by ELISA and confirmed by Western blot assay. The role of HBV infection in HIV-1 seroconversion was studied by stratification for sexual behavior and disease visit by visit. The adjusted risk ratio was 2.02 for hepatitis B surface antigen carriers and 2.14 for hepatitis-immune cases compared with hepatitis B-susceptible subjects. Similar results were obtained using a logistic regression model. After taking into account changes in sexual behavior and disease over time, the authors conclude that past HBV infection remains suspect as a cofactor or as a surrogate for other factors associated with HIV-1 seroconversion.

Blotting, Western↗
PubMed1993

Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study.

A cohort of 98 HIV-infected initially AIDS-free homosexual men from the Multicenter AIDS Cohort Study (MACS) was followed for 6 years to investigate whether CD8+ cell subsets have prognostic value for progression to AIDS. In the present study, four subsets of CD8+ T cells that previously have been shown to be selectively elevated in HIV-infected asymptomatic persons, specifically the CD8+ T cell subsets that were CD38+, HLA-DR+, CD57+ and L-selectin negative (Leu8-), were measured. Forty-nine of the 98 developed AIDS. Prognostic value of these CD8+ cell subsets was evaluated using the proportional hazards model. Levels of both CD38+ CD8+ and Leu8- CD8+ cells individually had prognostic value for progression to AIDS. In contrast, CD57+ CD8+ and HLA-DR+ CD8+ cell subsets levels did not have prognostic value. After adjustment for level of CD4+ T cells, however, only the elevation in the CD38+ CD8+ cell subset had additional prognostic value. These results suggest that the level of CD38+ CD8+ cells could be used together with the CD4+ T cell level to more accurately predict progression to AIDS among HIV-infected men. These results provide further support for the observation that dramatic and progressive activation of CD8+ T cells in HIV infection occurs. The power of elevated levels of the CD38+ CD8+ subset to predict poor prognosis in this cohort suggests these CD8+ T cells reflect an immune stimulation that is ultimately unable to control disease progression.

ADP-ribosyl Cyclase↗
PubMed1993

The relationship between T-cell levels and CMV infection in asymptomatic HIV-1 antibody-positive homosexual men.

To investigate the relationship between cytomegalovirus (CMV) infection and progression of HIV-1 disease, a group of 234 asymptomatic, HIV-1 antibody-positive homosexual men were examined for CMV isolation and levels of CMV IgM antibodies, CMV IgG antibodies, and CD4+ and CD8+ T-lymphocytes. CMV IgG antibodies were present in 100% and CMV IgM antibodies in 22% of the men. CMV was isolated from the semen of 45% of the men. No relationship was observed between CMV IgM antibodies and CMV in semen or CD4+ levels. CD4+ cell levels were significantly lower in those from whose semen CMV was isolated. In addition, an inverse relationship was observed between the concentration of CMV in semen and CD4+ levels. We postulate that the seminal tract may be a reservoir for systemic CMV infection in HIV-infected homosexual men. Reinfection from this or other sources may result in recurrent stimulation of HIV-1 replication and lead to a further decline in CD4+ cells. Clarification of whether persistent CMV infection is secondary to HIV-1-induced immunodeficiency or, conversely, promotes a more rapid decline in immunocompetency will require follow-up studies.

AIDS-Related Opportunistic Infections↗
PubMed1992

Predictors of the risk of development of acquired immunodeficiency syndrome within 24 months among gay men seropositive for human immunodeficiency virus type 1: a report from the Multicenter AIDS Cohort Study.

The natural history of infection with human immunodeficiency virus type 1 (HIV-1) is characterized by a relentless decline in CD4-positive lymphocytes and the ultimate development of acquired immunodeficiency syndrome (AIDS). However, variables other than the CD4-positive lymphocyte level contribute to the measurement of risk for AIDS and can be used as predictors of AIDS onset. This study was undertaken to identify factors that, independently of the CD4-positive lymphocyte level, would predict the risk of AIDS over 24 months in a cohort of HIV-1 seropositive homosexual men receiving no antiretroviral therapy. Demographic, clinical, and laboratory data from 1,325 white, HIV-1 seropositive participants in the Multicenter AIDS Cohort Study who have been studied for 4 years were analyzed with univariate and multivariate methods. To control for stage of infection, the baseline percentage of CD4-positive lymphocytes (a known marker of disease progression), and the decline of CD4-positive cells during the first 6 months of observation were used as continuous variables. The variables that were independently associated with an increased risk of developing AIDS were: low baseline CD4 percentage, decline in the CD4 percentage during the first 6 months of follow-up, the presence of serum immunoglobulin A at baseline, decrease in hemoglobin during the first 6 months of follow-up, incident fatigue, and the interaction of decline in the CD4 percentage and incident thrush. While low CD4 percentage and other variables have been previously described as prognostic markers, decline in the CD4 percentage and the interaction of that decline and incident thrush have not previously been described as being of prognostic importance. These variables and the analytic method for estimating prognosis may prove useful for selecting and evaluating antiretroviral therapy, instituting prophylactic measures against certain opportunistic infections, and recruitment into clinical trials. Because study participants received no antiretroviral prophylaxis during the period under analysis, the method could be used to estimate the prognosis for those receiving investigational treatment were they to remain untreated, effectively making any participant in a clinical trial his own untreated control.

Acquired Immunodeficiency Syndrome↗