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R Detels

Publications and source records attributed to R Detels.

At least 91 records · Page 5Linked to original sources
PubMed1996

Survival in HIV-infected patients who have received zidovudine: comparison of combination therapy with sequential monotherapy and continued zidovudine monotherapy. Multicenter AIDS Cohort Study Group.

BACKGROUND: Among patients who begin receiving zidovudine during intermediate-stage human immunodeficiency virus (HIV) infection, it is unclear whether changing to combination therapy (adding didanosine or zalcitabine) or sequential monotherapy (changing to didanosine or zalcitabine) significantly improves survival. OBJECTIVE: To determine, among patients who began receiving zidovudine during intermediate-stage HIV infection, the differential effects of changing to combination therapy (zidovudine with didanosine or zalcitabine) or sequential monotherapy (with didanosine or zalcitabine) or continuing zidovudine monotherapy. PATIENTS: 1077 HIV-seropositive men in the Multicenter AIDS (acquired immunodeficiency syndrome) Cohort Study who began receiving zidovudine before an AIDS-defining illness developed. SETTING: University-affiliated clinics in Baltimore, Chicago, Los Angeles, and Pittsburgh. DESIGN: Longitudinal cohort study, Treatment groups and important prognostic variables were modeled as time-dependent covariates in Cox proportional hazards models. MEASUREMENTS: Progression to AIDS and death. RESULTS: Compared with patients receiving continued zidovudine monotherapy, patients receiving combination therapy had a 45% improvement in survival (relative risk, 0.55 [95% Cl, 0.41 to 0.74; P < 0.001]) and patients who changed to sequential monotherapy had a 32% improvement in survival (relative risk, 0.68 [Cl, 0.52 to 0.89; P = 0.005]). In the landmark analyses, the median prolongation of survival associated with changing therapy was, at best, 3 to 6 months. Survival curves converged at 3.5 years for the 50 cells/mm3 disease-stage landmark, at 4.4 years for the 100 cells/mm3 landmark and at 4.9 years for the 150 cells/mm3 landmark. Mortality within these periods was 100%, regardless of treatment group or landmark. CONCLUSIONS: For patients who began receiving zidovudine during intermediate-stage disease, changing to either combination therapy or sequential monotherapy was associated with a statistically significant survival benefit compared with continuation of zidovudine monotherapy. The absolute increase in survival was modest, however, and long-term survival remained poor. Simultaneous time-dependent adjustment for changes in therapy and in important prognostic variables is necessary to derive relatively unbiased estimates of treatment effects in observational studies of HIV infection.

Antiviral Agents↗
PubMed1996

Survival from early, intermediate, and late stages of HIV infection.

OBJECTIVE: To estimate expected survival time among homosexual men infected with the human immunodeficiency virus type 1 (HIV-1) by (1) the calendar period before (1985-1988) and after (1989-1993) the widespread availability of acquired immunodeficiency syndrome (AIDS) treatments with antiretroviral and prophylactic interventions, and (2) stage of HIV disease. DESIGN: A prospective cohort study. A group of HIV-1-infected homosexual men were followed from July 1985 through June 1993 and evaluated every 6 months for the presence of clinical symptoms and measurement of the CD4 cell count. To measure the effectiveness of AIDS therapies in this nonrandomized study, we used 2 calendar periods as proxy measures of relative intensity of exposure to antiretroviral therapy. Stage of infection was defined by CD4 cell count and presence of HIV-related clinical symptoms or AIDS. SETTING AND STUDY PARTICIPANTS: Homosexual men infected with HIV-1 from the Multicenter AIDS Cohort Study. MAIN OUTCOME MEASURE: Survival time based on stage of HIV infection. RESULTS: The percentage of HIV-1-infected individuals free of AIDS and clinical symptoms at baseline who survived 2.5 years according to baseline CD4 cell counts of 0 to 0.100, 0.101 to 0.200, and 0.201 to 0.350 x 10(9)/L was 22%, 53%, and 83%, respectively, for the 1985-1988 calendar period, compared with 54%, 71%, and 91%, respectively, for men in the 1989-1993 calendar period. Among men free of AIDS with CD4 cell counts of greater than 0.350 x 10(9)/L, the relative hazard of mortality was 1.6 to 2.3 times higher for those with clinical symptoms compared with those free of clinical symptoms. CONCLUSIONS: Survival of AIDS-free HIV-1-infected individuals with CD4 cell counts of less than 0.350 x 10(9)/L has improved since antiretroviral and HIV prophylactic treatments have become available, but the long-term prognosis remains poor.

Antiviral Agents↗
PubMed1996

Elevated relative fluorescence intensity of CD38 antigen expression on CD8+ T cells is a marker of poor prognosis in HIV infection: results of 6 years of follow-up.

Relative fluorescence intensity measurements from a flow cytometer were used to evaluate expression of CD38 and HLA-DR antigens. These molecules are associated with cellular activation and are present at increased levels on the CD8+ lymphocytes of HIV-infected subjects. In the current study, the prognostic value of mean fluorescence intensity measurements of CD38 and HLA-DR on CD8+ cells was compared to results from our previous study in which we reported prognostic value for an elevated percentage of CD8+ cells that were positive for expression of the CD38 antigen (Giorgi et al.: JAIDS 6:904-912, 1993). Using the proportional hazards model, elevated mean fluorescence intensity of CD38 expression on CD8+ cells had prognostic value for development of AIDS that was almost identical to the prognostic value of the percentage of CD8+ cells that were positive for expression of CD38. This prognostic value was in addition to that provided by the patient's CD4+ cell measurement. To our knowledge, this is the first report that a measurement of fluorescence intensity can be used as a prognostic marker in an immunodeficiency disease. Efforts are needed to establish methods that will allow widespread application of this observation in the clinical management of HIV-infected subjects.

ADP-ribosyl Cyclase↗
PubMed1996

Persistently seronegative men from whom HIV-1 has been isolated are genetically and immunologically distinct.

Studies in both monkeys and humans have suggested that transient infection with HIV-1 can occur without provoking a measurable humoral immune response. The objective of this study was to look for genetic and immunologic correlates of transient HIV-1 infection in antibody-negative men from whom HIV-1 had been isolated. The distributions of MHC class I, class II, and TAP (transporter protein associated with antigen processing) region genes were compared between 23 persistently seronegative men from whom HIV-1 was isolated at least once (isol+/Ab-) and 137 men who seroconverted. A subset of 13 of the 23 isol+/Ab- men were compared to 27 seronegative men for distribution of CD25+CD4+ and CD25+CD8+ cells in the absence of exogenous immunologic stimulation. The prevalences of the TAP1.4, and a combination of TAP1.4, and TAP2.3 variants were significantly higher in the isol+/Ab- men. The proportion of CD8+ cells that expressed CD25+ antigen was also significantly higher in the isol+/Ab- men than in the seronegative men. We conclude that isol+/Ab- men may be genetically and immunologically distinct from HIV-1 susceptible men. We hypothesize that activated CD8+ cells may have cleared HIV-1 infection in these men through genetically mediated influences of the TAP genes on the presentation of peptides by HLA class I molecules.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection.

Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.

Acquired Immunodeficiency Syndrome↗
PubMed1996

KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma.

A major controversy regarding Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) is whether or not it is a ubiquitous infection of humans. Immunoassays based on KSHV- and Epstein-Barr virus (EBV)-coinfected cell lines show that most US AIDS-KS patients have specific antibodies to KSHV-related antigens. We have developed a sensitive indirect immunofluorescence assay (IFA) based on an EBV-negative, KSHV-infected cell line, BCP-1. When we used this IFA assay, KSHV-related antibodies were found in 71-88% of serum samples from US, Italian and Ugandan AIDS-KS patients, as well as all serum samples examined from HIV-seronegative KS patients. Although none of the US blood donors examined were KSHV seropositive by IFA, intermediate and high seroprevalence rates were found in Italian and Ugandan control populations. Antibody kinetics showed that more than half of the AIDS-KS patients who were examined IgG-seroconverted before KS development, and antibody levels did not decline after seroconversion. For these patients, seropositivity rates increased linearly with time, suggesting that the rate of infection was constant and that the risk of developing KS once infected with KSHV is not highly dependent on the duration of infection. These data strongly suggest that KSHV is not ubiquitous in most populations and that the virus may be under strict immunologic control in healthy KSHV-infected persons.

AIDS-Related Opportunistic Infections↗
PubMed1996

Risk factors for initiation of drug use among young males in southwest China.

To identify risk factors for drug use among young males in southwest China a cross-sectional survey and a non-concurrent cohort study were conducted. Demographic, behavioral and drug-use information was collected from young males aged 18-29 years. The non-concurrent cohort included the period 1 January 1991 to 1 August 1994. A total of 1548 subjects were interviewed. The cumulative incidence increased between 1991 and 1993. Multivariate analysis identified the following significant risk factors for drug use: being divorced/widowed/separated, having been encouraged by friends/others to try drugs, smoking cigarettes, belonging to the Jingpo ethnic group, and having a family member who used drugs in 1991. More than 6 years of education was a protective factor for drug use. Drug use in the community was associated with having been encouraged by friends or others to try drugs (71%), to smoking cigarettes (50%), and to belonging to the Jingpo group (24%). The results are consistent with community based prevention approaches which should be studied carefully because of the unique cultural and epidemiological situation in China.

Adolescent↗
PubMed1996

Use of antiherpes drugs and the risk of Kaposi's sarcoma: data from the Multicenter AIDS Cohort Study.

To determine if use of antiherpes drugs protects against the development of AIDS-associated Kaposi's sarcoma (KS), data from 935 homosexual men with AIDS from the Multicenter AIDS Cohort Study were analyzed. In nested case-control analysis, neither acyclovir use for human immunodeficiency virus infection (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.56-1.26; P = .39) nor acyclovir use for any indication (OR, 1.02; 95% CI, 0.76-1.38; P = .89) was associated with a reduced risk of KS as initial AIDS diagnosis. In longitudinal analysis, acyclovir was also not protective against developing KS as a late manifestation of AIDS (after initial non-KS AIDS diagnosis). Among men with cytomegalovirus disease, ganciclovir use (relative risk [RR], 0.56; 95% CI, 0.22-1.44; P = .23) and foscarnet use (RR, 0.40; 95% CI, 0.051-3.10; P = .38) were associated (although not significantly) with a reduced risk of KS. Thus, acyclovir use does not appear to reduce the risk of KS, but further study of other antiherpes drugs such as ganciclovir and foscarnet is warranted.

AIDS-Related Opportunistic Infections↗
PubMed1996

Risk factors for intravenous drug use and sharing equipment among young male drug users in Longchuan County, south-west China.

OBJECTIVES: To identify the risk factors for intravenous drug use and sharing of equipment in Longchuan County in south-west China. METHODS: Demographic information and sexual and drug-use-related behavior between 1 January 1991 and 1 August 1994 were collected retrospectively from a cohort of young male drug users aged 18-29 years in 82 villages. RESULTS: A total of 433 drug users were identified. The cumulative incidence of intravenous drug use was 40.0% during the 3.7-year study period. The annual incidence increased from 10% in 1991 to over 30% in 1994. Risk factors for intravenous drug use among drug users, according to the multivariate model, included having had premarital/extramarital sex [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.01-2.3], having a family member who used drugs in 1991 (OR, 1.8; 95% CI, 1.1-2.9), and currently not married (OR, 1.6; 95% CI, 0.98-2.7). Being Buddhist protected against intravenous drug use (OR, 0.4; 95% CI, 0.2-0.9). The population attributable fraction was 30% for not being currently married, 17% for having had premarital/extramarital sex and 14% for having a family member who used drugs. The risk factor for sharing of equipment was being of Jingpo ethnicity (OR, 5.8; 95% CI, 2.5-13.8). The average incidence of sharing equipment was 19.6% per year. The population attributable fraction for sharing equipment was 58.5% for being Jingpo. CONCLUSIONS: The incidence of intravenous drug use and sharing equipment is increasing. Therefore, it is urgent that vigorous, effective intervention programs be initiated in southern Yunnan. Unmarried, sexually promiscuous Jingpo drug users with a family history of drug use should be especially targeted. Given the problems of transport and communication in this remote area of China, intervention programs which use existing social, governmental and community networks should be implemented.

Adolescent↗
PubMed1996

Rapid evolution of human immunodeficiency virus strains with increased replicative capacity during the seronegative window of primary infection.

The relationship between host and virus was examined during the initial stages of human immunodeficiency virus type 1 (HIV) infection in a volunteer from the Multicenter AIDS Cohort Study (MACS). The individual was asymptomatic and unaware of his infection during an initial donation of blood and inguinal lymphoid tissue. Proviral DNA, however, was present in cells from both sources, HIV RNA was detected in the plasma, and CD4+ cell levels were reduced by approximately 50% compared with previous donations in the MACS. In a second blood donation 12 days later, plasma HIV RNA increased 200-fold in tandem with viral isolates with an increased growth phenotype in vitro. HIV burden was ultimately suppressed upon seroconversion and the emergence of HIV-specific CD8+ cytotoxic T lymphocytes. These observations provide further evidence that the potential benefits of early treatment may be maximized during the early stages of infection, when viral fitness may be low but is unopposed by immune responses.

CD4-Positive T-Lymphocytes↗
PubMed1996

High risk behavior related to HIV transmission among recently diagnosed TB patients in Jakarta.

This study investigated the demographic and high risk behavior characteristics among recently diagnosed pulmonary tuberculosis patients aged 18-40 years old in Jakarta, Indonesia. Three hundred and four participants were recruited voluntarily from two general hospitals. Among the study population, 38.5% were unemployed, 69.7% were in low socio-economic condition, and 69.7% had a high school or higher level of education. About 8% had received a transfusion, 0.3% were intravenous drug users (IVDU) and had sex with other IVDU's no males admitted to being homosexual, 3.2% of males were bisexual, 20.1% (35.5% of males, 4% of females) engaged in extramarital heterosexual intercourse, and 3.6% (7.1% of males) had one or more sexually transmitted diseases (STD). We found very strong associations between gender and extramarital heterosexual activity (p < 0.001, prevalence odds ratio (POR 13.11), between occupation and extramarital heterosexual activity (p < 0.001, POR 3.84), and between extramarital heterosexual contact and a history of an STD (p < 0.001, POR 20.86). High risk activities were common among these TB patients, especially among males. These results suggests that the necessary social conditions for transmission of HIV are common in Jakarta.

Adult↗
PubMed1995

Natural killer cell immunodeficiency in HIV disease is manifest by profoundly decreased numbers of CD16+CD56+ cells and expansion of a population of CD16dimCD56- cells with low lytic activity.

Natural killer (NK) cells were enumerated by three-color immunofluorescence in 255 uninfected and 399 human immunodeficiency virus-infected adults. Several dramatic alterations were observed. First, the median number and percentage of CD16+CD56+ NK cells, the subset that comprises > 90% of the NK cells in healthy adults, were severely decreased (median, 175/mm3 in uninfected controls; 63/mm3 in HIV-infected non-AIDS subjects). Even subjects with > 800 CD4+ cells/mm3 had decreased CD16+CD56+ NK cell levels (97/mm3). Second, the number of CD16+CD56- cells, an NK population that is rare in healthy adults, was elevated (median, 20/mm3 in uninfected controls; 64/mm3 in HIV-seropositive non-AIDS subjects). Third, the expression of CD16 on the NK cells was markedly reduced; some CD56+ cells and virtually all CD56- cells were CD16dim. Fourth, fluorescence-activated cell-sorting studies revealed little NK- or antibody-dependent cellular cytotoxic activity in the CD16dimCD56- cell population. These results indicate that the pathogenesis of HIV disease includes numerical alterations in subpopulations of NK cells. A better understanding of how HIV infection causes this aspect of pathogenesis is needed.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Evaluation of secular trends in CD4+ lymphocyte loss among human immunodeficiency virus type 1 (HIV-1)-infected men with known dates of seroconversion.

The rate at which immunodeficiency develops in untreated human immunodeficiency virus type 1(HIV-1)-infected persons might be increasing or decreasing over time because of viral evolution or other factors. Beginning in 1984, Multicenter AIDS Cohort Study investigators recruited HIV-1-seronegative homosexual/bisexual men from four US metropolitan areas and examined them semiannually for HIV-1 seroconversion. To assess possible secular changes in the natural history of HIV-1 infection, the authors examined CD4+ lymphocyte data from 354 men who seroconverted between 1984 and 1991. To control for measurement differences among centers and over time, the authors adjusted CD4+ lymphocyte values to those of persistently seronegative participants. CD4+ lymphocyte percentage measurements at the first seropositive visit formed a U-shaped pattern, with the lowest values observed in 1988 and 1989. The authors observed no consistent secular pattern of CD4+ percentages at later visit dates, except that mean CD4+ percentages were consistently lowest in men who seroconverted in 1988. In a proportional hazards model, the time to the adjusted CD4+ lymphocyte count of < 500 cells/mm3 was not associated with the secular time of seroconversion (relative hazard = 1.05, 95% confidence interval 0.97-1.13). The authors' data do not suggest a major change in the natural history of HIV-1 infection of this population.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Prognostic factors in human immunodeficiency virus-positive patients with a CD4+ lymphocyte count < 50/microL.

This analysis investigated variability of survival time in a cohort of 553 human immunodeficiency virus type 1 (HIV-1)-infected homosexual or bisexual men with < 50 CD4+ cells/microL. Median survival after the first CD4+ cell count < 50/microL was 1.34 years; 25% survived > or = 2 years. Multivariate analysis showed longer survival with concurrent acyclovir and zidovudine use, hemoglobin > or = 12 g/dL, and full-time employment (P < .0001). Other significant covariates associated with longer survival included African-American race, no prior AIDS illness, weight loss < 4.5 kg, and zidovudine use (with or without concurrent acyclovir) after CD4+ cells fell to < 50/microL. An easily derived score identified Multicenter AIDS Cohort Study subjects likely to survive > 2 years after CD4+ cell count was < 50/microL. Survival once CD4+ cell count fell below 50/microL may be longer for persons with a good performance status and specific clinical markers. Health care providers should consider these variables in decision-making strategies and design of clinical trials.

Acyclovir↗