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Biomedical subjects

J Raboud

Publications and source records attributed to J Raboud.

32 records · Page 2Linked to original sources
PubMed1997

Stavudine plus lamivudine in advanced human immunodeficiency virus disease: a short-term pilot study.

The short-term effects of stavudine (d4T) plus lamivudine (3TC) were evaluated among 48 human immunodeficiency virus-infected patients for whom zidovudine therapy had failed or who could not tolerate zidovudine. Patients were followed for 8 weeks after initiation of open-label d4T plus 3TC. Four patients discontinued therapy, because of neutropenia (1), hepatitis (1), or neuropathy (2). Reduction in virus load was -0.86 (+0.3 to -3.4) log10 copies/mL and CD4 cell increase was 30 (-100 to +290) cells/mm3. Virologic response was associated with a higher CD4 cell count, no prior exposure to d4T and 3TC, and no previous AIDS-defining illness. Virus load reduction for patients naive to 3TC and d4T was -1.47 (-0.14 to -3.37) log10 copies/mL. Short-term use of d4T plus 3TC is safe, well-tolerated, and associated with virologic and substantial immunologic benefits. Further evaluation of d4T and 3TC in combination is warranted.

Adult↗
PubMed1997

Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus infection. INCAS Study Group. Italy, Netherlands, Canada, Australia, and (United) States.

The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.

Biopsy↗
PubMed1996

Double-blind placebo-controlled pilot trial of acemannan in advanced human immunodeficiency virus disease.

SUMMARY: We assessed the safety and surrogate markers' effect of acemannan as an adjunctive to antiretroviral therapy among patients with advanced HIV disease receiving zidovudine (ZDV) or didanosine (ddI) in a randomized, double-blind, placebo-controlled trial of acemannan (400 mg orally four times daily). Eligible patients of either sex had CD4 counts of 50-300/microl twice within 1 month of study entry and had received 26 months of antiretroviral treatment (ZDV or ddI) at a stable dose for the month before entry. CD4 counts were made every 4 weeks for 48 weeks. P24 antigen was measured at entry and every 12 weeks thereafter. Sequential quantitative lymphocyte cultures for HIV and ZDV pharmacokinetics were performed in a subset of patients. Sixty-three patients were randomized. All were males (mean age 39 years). The mean baseline CD4 counts were 165 and 147/microl in the placebo and acemannan groups, respectively; 90 percent of the patients were receiving ZDV at entry. Six patients in the acemannan group and five in the placebo group developed AIDS-defining illnesses. There was no statistically significant difference between the groups at 48 weeks with regard to the absolute change or rate of decline at CD4 count. Among ZDV-treated patients, the median rates of CD4 change (ACD4) in the initial 16 weeks were - 121 and - 120 cells per year in the placebo and acemannan groups, respectively ( p = 0.45), ACD4 from week 16 to 48 was 0 and - 61 cells per year in the acemannan and placebo groups (p = .11), respectively. There was no statistical difference between groups with regard to adverse events, p24 antigen, quantitative virology, or pharmacokinetics. Twenty-four patients, 11 receiving placebo and 13 receiving acemannan, discontinued study therapy prematurely, none due to serious adverse reactions. Our results demonstrate that acemannan at an oral daily dose of 1600 mg does not prevent the decline in CD4 count characteristic of progressive HIV disease. Acemannan showed no significant effect on p24 antigen and quantitative virology. Acemannan was well tolerated and showed no significant pharmacokinetic interaction with ZDV.

Administration, Oral↗
PubMed1995

Didanosine compared with continued zidovudine therapy for HIV-infected patients with 200 to 500 CD4 cells/mm3. A double-blind, randomized, controlled trial. Canadian HIV Trials Network Protocol 002 Study Group.

OBJECTIVE: To compare the safety and efficacy of didanosine with that of continued zidovudine therapy in persons with human immunodeficiency virus (HIV) infection who had received zidovudine for at least 6 months and had CD4 cell counts of 200 to 500 CD4 cells/mm3. DESIGN: Double-blind, randomized controlled trial. SETTING: 10 Canadian university-affiliated specialty clinics. PATIENTS: 246 patients were assigned to receive standard doses of either zidovudine or didanosine. OUTCOME MEASURES: The primary clinical end point was the occurrence of a new, previously undiagnosed acquired immunodeficiency syndrome (AIDS)-defining illness or death. RESULTS: 245 of 246 patients were eligible (118 receiving didanosine and 127 receiving zidovudine). Sixty-six percent were asymptomatic, 30% had AIDS-related complex, and 4% had AIDS. The median baseline CD4 count was 320 cells/mm3. The median previous duration of zidovudine therapy was 471 days. Nine new AIDS-defining illnesses developed during the study; all but one were in the zidovudine group (relative risk, 7.9 [95% CI, 1.0 to 63.3; P = 0.02]). A change to didanosine led to a statistically significant increase in CD4 counts by week 2 that persisted until the end of the study at week 48 (P < or = 0.01). Viral sensitivity studies (done in 102 patients) showed that 28% of the zidovudine group and 21% of the didanosine group had high-level in vitro resistance to zidovudine (50% inhibitory concentration greater than 0.8 microM) at baseline (P = 0.49). Only one patient in the didanosine group developed high-level resistance to zidovudine during the study. In the zidovudine group, the cumulative probability of developing high-level resistance to zidovudine was 59% at 1 year (P = 0.01). Abdominal pain, leukopenia, and neutropenia were more frequent in the zidovudine group, and hyperuricemia was more frequent in the didanosine group (P < 0.05). CONCLUSION: In clinically stable patients with 200 to 500 CD4 cells/mm3 who had tolerated zidovudine for at least 6 months, a change to didanosine led to a decrease in the rate of disease progression, a sustained increase in CD4 counts, and a decrease in the chances of developing high-level resistance to zidovudine. Both drugs were generally well tolerated.

Adult↗
PubMed1995

Potential applications of proviral load measurement in clinical retrovirology.

We have previously noted an association between proviral load and the severity of immune disease in individuals with a wide range of CD4 cell counts. Using the quantitative DNA polymerase chain reaction technology developed in our laboratory, we sought to extend these observations, with a view to establishing guidelines for the use of proviral load in a clinical context. We studied 199 patients with a range of CD4 cell counts attending an urban tertiary care center. Proviral load/10(6) peripheral blood mononuclear cells (PBMCs) was measured using a microtiter plate assay designed specifically for this purpose. Human immunodeficiency virus proviral DNA was detected in 193 of 199 clinical samples. Levels of proviral load were tabulated for patients and evaluated in seven categories defined by CD4 cell counts. Although a wide range of proviral loads was observed in each category of patients, there was a trend toward increasing proviral load with decreasing CD4 cell count. Statistically significant relationships were observed between proviral load and the CD4 cell count and the CD4 cell percentage (Spearman's correlation coefficient -0.19, p = 0.01 for both absolute CD4 and CD4 percentage). These relationships were quite weak and could not be taken to explain disease progression in isolation. If we defined a cutoff between low and high proviral loads at 100 copies/10(6) PBMCs, we noted that 52% (24 of 46) of patients with CD4 cell counts > 400/microliters had lower loads, as compared with 16% (24 of 143) of those with more advanced disease (p < 0.01). There is a weak, but statistically significant association between proviral load and CD4 cell depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4 Lymphocyte Count↗
PubMed1992

Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗
PubMed1991

A comparison of health-related quality-of-life measures for rheumatoid arthritis research. The Auranofin Cooperating Group.

Twenty-eight instruments measuring pain, clinical, functional, and global characteristics were administered to 303 patients in a six-month randomized clinical trial of auranofin and placebo in the treatment of patients with rheumatoid arthritis. The instruments were compared with respect to their responsiveness in detecting a treatment effect, the time involved in administering the instrument, the need for the presence of an interviewer, and ease of administration. The instruments' ability to detect a treatment effect was the deciding characteristic in the clinical, pain, and global categories in choosing the preferred instrument. The counts of tender and swollen joints were found to be the most responsive clinical measures, the 10-cm pain line was the most responsive and the fastest to administer of the pain instruments, and the categorical self-assessment of arthritis was the most responsive global measure. In the functional ability category, the Health Assessment Questionnaire (HAQ), the Keitel Functional Assessment, and the Quality of Well-Being (QWB) Questionnaire were equally responsive. The HAQ was the shortest and the only self-administered questionnaire. The QWB has had the most extensive validation work but was a complex instrument requiring intensive interviewer training. The Keitel was the most time-consuming instrument, but had the advantage of high interobserver agreement. The design of future trials can be guided by the information obtained in this study on their relative efficiencies and ease of use.

Adult↗
PubMed1991

Clinical utility and specificity of anticardiolipin antibodies.

Established solid phase assays for anticardiolipin antibodies (aCL) are often characterized by high levels of nonspecific binding. As a result, only very high levels of aCL have been reported to be associated with a variety of clinical conditions including systemic lupus erythematosus (SLE), recurrent intravascular thrombosis and unexplained recurrent fetal loss. We have developed an ELISA replacing direct evaporation of soluble cardiolipin with cardiolipin micelles in physiological saline as the antigen binding step in the assay. Levels of IgG aCL were detected in various sera at dilutions of 1/100 to 1/3200, showing improved assay sensitivity. Assay specificity was determined using double stranded DNA and ovalbumin as irrelevant binding antigens and no crossreactivity was found. The controversial use of Tween 20 in the assay was investigated and results showed it decreases nonspecific binding without interfering in antibody detection. This assay has enabled us to identify differences in the prevalence and level of aCL antibodies in sera from healthy nonpregnant controls (0/25 positive), healthy pregnant controls (5/47 positive for IgG and 8/47 positive for IgM) and from women with unexplained recurrent fetal loss (16/62 and 14/62 positive, respectively). We support the observation that aCL are not normally distributed, and therefore nonparametric methods of statistical analysis are necessary to determine population prevalence. We confirm that aCL IgM are a relatively nonspecific finding, and extreme caution must be used in basing any clinical decisions on the presence of this antibody alone.

Adolescent↗
PubMed1991

Comparison of three HIV antigen detection kits in sequential sera from a cohort of homosexual men.

HIV antigen detection kits are available from a number of commercial sources. Abbott, Coulter, and Du Pont antigen kits were used to test 661 sera collected sequentially from 65 members of the Toronto Sexual Contact Study (TSCS). The sera had been collected at 3-month intervals over 4 years from nine persistently HIV-seronegative men, 14 seroconverters, and 42 seroprevalent participants. Antigen was not detected in any seronegative men. Two of 14 seroconverters were antigen positive in the specimen immediately preceding seroconversion (by all kits). Antigen was detected in 22 of 56 seropositive participants; of these, 16 of 22 demonstrated the emergence of antigen during observation. Discrepancies were noted in the time of detection of antigen (ranging from 3 months to more than 3 years) in nine participants. Although overall concordance among all kits for all specimens appears high (95.4%), when the bias introduced by testing multiple specimens from the same patient is removed, the lower bound of concordance among all three kits is estimated to be 80%. Similarly, after correction, the upper and lower bound of estimates of sensitivity are Abbott 96, 92%; Coulter 88, 63%; and Du Pont 88, 58%. There are significant differences in the performance characteristics of these commercial products for the detection of HIV antigen in serum.

AIDS-Related Complex↗
PubMed1990

Tubal sterilization and the long-term risk of hysterectomy.

To assess the effect of tubal sterilization on the risk of hysterectomy, we studied 7414 women aged 20 to 49 years who had had a tubal sterilization at a health maintenance organization between January 1, 1968, and December 31, 1983. Compared with a population-based cohort of nonsterilized women, women sterilized while 20 to 29 years old were 3.4 times more likely to have had a subsequent hysterectomy (95% confidence interval, 2.4 to 4.7). Adjustment for the effects of potential confounders with a subset of 276 women did not appreciably alter this association. For multivariate comparisons with 5323 wives of vasectomized men, there was no significant elevation in the risk of hysterectomy following sterilization among women sterilized while 20 to 29 years old. Tubal sterilization was not associated with hysterectomy for married women who underwent tubal sterilization at age 30 or older. These results do not support a biological basis for the relationship between tubal sterilization and hysterectomy.

Adult↗
PubMed1990

Cofactors of progression to acquired immunodeficiency syndrome in a cohort of male sexual contacts of men with human immunodeficiency virus disease.

In a cohort of 249 male sexual contacts of men with acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition in Toronto, Ontario, Canada, 143 cohort members were seropositive on enrollment and 16 seroconverted between initial recruitment in July 1984 to July 1985 and December 1988. Data on age, smoking and drinking status, recreational drug use, and history of sexually transmitted diseases and other diseases were obtained from interviews at induction and during follow-up on the cohort members every 3 months. Cox relative risk regression models, in which time was calculated from estimated date of human immunodeficiency virus (HIV) infection for seroprevalent cohort members and from 90 days prior to the first positive test for seroconverters, examined the potential effect of use of a variety of recreational drugs and the occurrence of selected infections on the risk of development of AIDS. Thirty-five cohort members developed AIDS while under study. No significant association with risk of progression to AIDS was noted for use of various recreational drugs (singly or in combination), history of specific infections, age at enrollment, or smoking and drinking status at enrollment. Only estimated duration of HIV infection appeared to be associated with increasing risk of development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Efficiency gains from the addition of controls to matched sets in cohort studies.

We evaluate relative efficiencies of added controls in matched cohort studies in terms of the asymptotic variance of the estimate of the log relative risk associated with a single binary exposure variable. We calculate expected contributions to the information based on the Cox proportional hazards model under the assumption that the failure times for exposed and unexposed individuals have independent exponential or Weibull distributions and that the censoring variable, when present, also has an exponential distribution or a Weibull distribution with a shape parameter common to that of the failure time distribution. With estimation of a relative risk of four or less, one gains little with an increase in the ratio of unexposed to exposed cohort members beyond five or so.

Cohort Studies↗
PubMedDate not supplied

Needle sharing behaviour among injection drug users (IDUs) in treatment in Montreal and Toronto, 1988-1989.

Injection drug users (IDUs) entering treatment programs in Montreal and Toronto were recruited for a study of drug using behaviour and risk of HIV infection. Only those who had injected within 6 months of entering their treatment program were eligible for participation. 183 subjects were recruited in Montreal and 167 in Toronto between November, 1988 and October, 1989. Each participant completed a standardized interviewer-administered questionnaire which focussed on, among other things, drug history and needle sharing behaviour. Approximately three-quarters of respondents in both cities reported sharing needles and syringes within the 6-month period prior to their entry into treatment. Our analysis, which focussed on variables associated with needle sharing revealed that having a sexual partner who injected, trouble obtaining sterile needles and syringes and cocaine injection were significantly and independently associated with needle sharing in a logistic regression model which also controlled for city of recruitment.

AIDS Serodiagnosis↗