Time for realism over HIV infection.
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Congresses as Topic↗
Biomedical subjects
M T Schechter
Publications and source records attributed to M T Schechter.
Rates of prescribing zidovudine post Concorde Trial.
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British Columbia↗
Impact of HIV infection and AIDS on death rates in British Columbia and Canada.
OBJECTIVE: To assess the impact of HIV infection and AIDS on death rates in British Columbia and Canada. DESIGN: Descriptive, population-based study. SETTING: British Columbia and Canada. PATIENTS: All people for whom HIV infection or AIDS was listed as the underlying cause of death in Canada and all provinces from 1987 to 1991, as reported to Statistics Canada, and all people for whom HIV infection or AIDS was listed as the underlying or antecedent cause of death in British Columbia and Vancouver from 1987 to 1992, as reported to the Division of Vital Statistics, British Columbia Ministry of Health. MAIN OUTCOME MEASURES: Age- and cause-specific patterns of death, and potential years of life lost (PYLLs) for men. RESULTS: From 1987 to 1991 a total of 4189 deaths from HIV infection and AIDS (in 3941 males and 248 females) in Canada and 686 such deaths (in 671 males and 15 females) in British Columbia were reported to Statistics Canada. The rate of death from HIV infection and AIDS was 1.39 times higher (95% confidence interval [CI] 1.29 to 1.50) in British Columbia than in Canada as a whole and 1.95 times higher (95% CI 1.65 to 2.29) when HIV infection was associated with specified malignant neoplasms than with other related causes. The PYLLs from HIV infection and AIDS for men rose steadily in Canada, from 17,615 in 1987 to 38,735 in 1991; the latter is comparable to the PYLLs from stroke and colorectal cancer. In Vancouver the PYLLs from HIV infection and AIDS for men increased sharply from 1987 to 1992, surpassing the PYLLs from heart disease, malignant neoplasms and accidents. CONCLUSIONS: From 1987 to 1991 the rate of death from HIV infection and AIDS in British Columbia was higher than the national average. In Vancouver HIV infection and AIDS have become the leading causes of premature death in men, exceeding heart disease, malignant neoplasms and accidents.
Acquired Immunodeficiency Syndrome↗
Higher socioeconomic status is associated with slower progression of HIV infection independent of access to health care.
In order to identify socioeconomic characteristics associated with slower progression of HIV infection, we conducted a nested case-control study within a cohort of 729 homosexual men. The study compared non-progressors (defined as subjects who, at a follow-up visit during the period October 1989-December 1990, had been HIV positive for at least 5 years, had a CD4 count > 0.5 x 10(9)/l, had a Karnofsky score of 100%, were at Centers for Disease Control (CDC) Stage III or less, and had never received zidovudine or prophylaxis against Pneumocystis carinii pneumonia) with rapid progressors (defined as those who had developed AIDS other than Kaposi's sarcoma within 6 years of seroconversion, or within 5 years of enrollment if already seropositive). Rapidly progressing subjects were matched to non-progressing subjects on the basis of date of enrollment if seroprevalent and date of seroconversion if seroincident. Socioeconomic data were taken from the questionnaire obtained at enrollment into the cohort during 1982-84. There were 41 subjects in each group. A significantly higher proportion of the non-progressors had annual incomes above $10,000, at enrollment (85 vs 62%; p = 0.019). Similarly, a greater proportion of the non-progressors were more likely to have finished secondary school (100 vs 84%; p = 0.020) than rapid progressors. A higher proportion of non-progressors reported employment in management and professional positions (35 vs 15%). The non-progressing group also had a significantly higher socioeconomic index based on self-reported occupation (45.1 vs 38.3; p = 0.035). The association with higher income persisted even after adjustment for baseline CD4 count and symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
Acquired Immunodeficiency Syndrome↗
Outmigrant ascertainment for bias assessment in environmental epidemiology.
BACKGROUND: In the summer of 1985, the McGill Epidemiology Rapid Response Unit undertook a study comparing two areas exposed to emissions of 'sour gas' refineries to an unexposed area. One operational objective of the project was the identification and survey of all the people who had lived in the study area but had since moved (outmigrants). METHODS: We estimated the number of outmigrants (people who had ever lived in the area during the period 1957 to 1985) to be 3363 by using information obtained from our cross-sectional survey and from population statistics for the area of interest. Ten different methods combined lead to the identification of approximately 87% of all the outmigrants who left the study area during that period. We used vital statistics to identify the outmigrants who had died and mailed questionnaires to obtain the necessary information from the others. RESULTS: We confirmed the vital status of approximately 46% of them (1532/3363). The results from the outmigrant survey showed that they were younger than area residents, that they experienced lower rates of heart disease and hypertension and that they had moved for health reasons in only 1.3% of the cases. These findings were similar across comparison areas. CONCLUSION: We concluded that there was no effect due to migration bias on the cross-sectional study results. This evidence considerably strengthened the conclusions regarding the effects of exposure, a benefit that largely justified the cost of identifying and surveying the outmigrants.
Adolescent↗
The changing spectrum of AIDS index diseases in Canada.
OBJECTIVE: To describe the changing spectrum of AIDS index diseases in Canada over a 10-year period from 1981 to 1991. DESIGN: A descriptive, population-based study. SETTING: Canada. PATIENTS: All cases of AIDS in Canada reported by the Division of HIV/AIDS Epidemiology of the Department of National Health and Welfare. MAIN OUTCOME MEASURES: Age-standardized rates of initial AIDS manifestations (1987 Centers for Disease Control and Prevention case definition), by year of diagnosis among adults in Canada. RESULTS: A total of 6641 adult AIDS cases were examined. The rate of Pneumocystis carinii pneumonia (PCP) peaked in 1989 with a rate of 3.18 per 100,000, declining to 2.74 per 100,000 in 1991 (P = 0.894). Similarly, the rate of Kaposi's sarcoma (KS) stabilized during this interval from 1.06 per 100,000 in 1987 to 1.14 per 100,000 in 1991 (P = 0.189). In contrast, the rates of all other AIDS-defining illnesses increased from 1.48 per 100,000 in 1987 to 3.43 per 100,000 in 1991 (P = 0.001). For these other AIDS index diseases, significant rate increases were observed for esophageal candidiasis, cytomegalovirus (CMV) diseases, wasting syndrome, toxoplasmosis, and Mycobacterium avium complex (MAC) disease. CONCLUSIONS: Our study shows a leveling and decline in incidence of KS and PCP, respectively, and a concomitant increase of other diagnoses, especially esophageal candidiasis, CMV, wasting syndrome, toxoplasmosis, and MAC disease in Canada. These findings highlight the importance of developing specific strategies to prevent emerging AIDS index diseases and serve as a cautionary note to practicing clinicians, indicating the relative widening of the spectrum of HIV index diseases.
AIDS-Related Opportunistic Infections↗
Indirect costs of HIV/AIDS mortality in Canada.
OBJECTIVE: To estimate and compare the societal impact of HIV infection and AIDS with other selected causes of male mortality in terms of the indirect costs of future production lost. DESIGN: Descriptive, population-based economic evaluation study. PATIENTS: All men aged 25-64 years for whom HIV/AIDS or another selected disease was listed as the underlying cause of death in Canada from 1987 to 1991, as reported to Statistics Canada. SETTING: Canada. MAIN OUTCOME MEASURES: Present value of future earnings lost for men using a human capital approach based on potential years of life lost in men aged 25-64 years. RESULTS: Assuming a 2% annual growth in earnings and a 3% annual real discount rate, the present value of the total loss of future production for all men aged 25-64 years who died in Canada during 1987-1991 was estimated to be 39.74 billion 1990 US$. Deaths due to HIV/AIDS accounted for 5.3% of this total loss or 2.11 billion in 1990 US$. Future production loss due to HIV/AIDS more than doubled during the period from 1987 to 1991, from 0.27 to 0.60 billion 1990 US$. The loss in future earnings attributable to HIV/AIDS was exceeded only by that of ischaemic heart disease (15.2%), suicide (9.4%), motor vehicle accidents (6.6%), and lung cancer (6.6%). In total, these five causes of death accounted for 43.1% of the total indirect cost of production lost for men aged 25-64 years during the 5-year period. CONCLUSION: Our findings demonstrated HIV/AIDS mortality is already having a dramatic impact on future wealth production in Canada. If the past trend continues, the production lost in 1994 should exceed 0.86 billion 1990 US$ and will account for more than 10% of the total annual loss for men aged 25-64 years.
Acquired Immunodeficiency Syndrome↗
Increasing age is associated with faster progression to neoplasms but not opportunistic infections in HIV-infected homosexual men.
OBJECTIVE: To characterize the associations of age and progression rates to AIDS-defining neoplasms and opportunistic infections (OI) in HIV-infected homosexual men. METHODS: Data from 407 homosexual men with documented dates of HIV seroconversion participating in cohort studies from four geographic locations were merged. Kaplan-Meier and Cox proportional hazards analyses were conducted with respect to the association of age with time from seroconversion to the first AIDS-defining neoplasm and OI. RESULTS: Among the 407 participants, 139 (34%) were diagnosed with AIDS; 45 (11%) with neoplasms and 90 (22%) with OI. Older age at seroconversion was significantly associated with faster progression to neoplasms, but not to OI. For each 10-year increase in age the risk for neoplasms increased 1.65-fold [95% confidence interval (CI), 1.12-2.43], after adjustment for clinical treatments. For OI this risk estimate was 0.98 (95% CI, 0.72-1.34). CONCLUSIONS: Increasing age is associated with faster progression to AIDS-defining neoplasms, but not with progression to OI. This has not been previously reported and may explain conflicting results in other studies among homosexual men that considered AIDS as a single entity. Our findings suggest that age and AIDS manifestations should be considered, particularly in the context of natural history studies, clinical trials and mathematical modelling.
AIDS-Related Opportunistic Infections↗
Decreasing frequency but worsening mortality of acute respiratory failure secondary to AIDS-related Pneumocystis carinii pneumonia.
OBJECTIVE: To describe changes in incidence and outcome of acute respiratory failure (ARF) due to AIDS-related Pneumocystis carinii pneumonia (PCP) at a tertiary care center over the 4-year period starting April 1, 1987 with reference to previously reported data from the preceding 6 years. METHODS: All patients admitted to St. Paul's hospital with a diagnosis of AIDS-related PCP during the study period were reviewed with regard to diagnostic, clinical, therapeutic, and outcome variables. RESULTS: A total of 456 episodes of PCP were diagnosed during the study period. These were compared against 127 cases diagnosed between 1981 and 1987. The frequency of hospitalization for PCP decreased to 78% in 1987 to 1991 from 100% in 1981 to 1987 (p < or = 0.001). A similar decreasing trend was observed with regard to the incidence of PCP-related ARF that declined from 21% in 1981 to 1987 to 9% in 1987 to 1991 (p = 0.009). Despite this, overall PCP-related mortality remained stable at 12% in 1981 to 1987 and 9% in 1987 to 1991 (p = 0.26). The proportion of patients with PCP-related ARF who received mechanical ventilation decreased from 89% in 1981 to 1987 to 64% in 1987 to 1991 (p < 0.001). Despite this, the case fatality rate among mechanically ventilated patients increased from 50% in 1981 to 1987 to 89% in 1987 to 1991 (p = 0.003). These changes were associated with a significant change in the pattern of use of corticosteroids as adjunctive therapy for AIDS-related PCP. In 1985 to 1986, nearly 100% of patients admitted to the ICU received corticosteroids only after admission to the ICU, following the development of ARF. In contrast, in 1989 to 1990, 50% of patients were admitted to the ICU already receiving systemic corticosteroids. The rise in the proportion of patients receiving corticosteroids prior to ICU admission between these two intervals was statistically significant (p = 0.017). CONCLUSION: Our data show a decreasing frequency but a worsening mortality of ARF secondary to AIDS-related PCP. We conclude that ARF secondary to AIDS-related PCP developing despite maximal therapy, including adjunctive corticosteroids, carries a dismal prognosis.
AIDS-Related Opportunistic Infections↗
Aetiology of AIDS.
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Acquired Immunodeficiency Syndrome↗
Use of backcalculation for estimation of the probability of progression from HIV infection to AIDS.
Backcalculation has been used to estimate the rate of past HIV infection and to predict future AIDS incidence. In this study we examine another use: estimating the probability of progression from HIV infection to AIDS as a function of time from infection. Given observed AIDS incidence data, the technique of backcalculation estimates the most likely number of persons infected with HIV in the past. Assumptions about probability of progression from HIV infection to AIDS are necessary. By varying these assumptions and examining the resulting goodness of fit to the AIDS incidence data, we can theoretically estimate parameters of progression. We report on implementation of this method and examine its practical utility in deciding among four competing progression models specified on a priori grounds. The four specific models comprise three Weibull distributions with medians of 8, 10, and 12 years, respectively, and one model that begins as a Weibull with 8 year median but where the hazard is level after 3.5 years. To employ asymptotic maximum likelihood methods, we define a two parameter family of progression models that includes all four a priori models. One parameter sets the scale for an initial Weibull progression (the shape parameter being fixed for all models), and the other specifies a levelling point after which the hazard remains constant. AIDS incidence data from Canada's national surveillance system provided the empiric data for this evaluation. First we corrected these data for reporting delay by Poisson modelling of the delay distribution. We used three parametric families of infection curves: step-function, log-logistic, and logistic. The results support the hypothesis of an early levelling of the hazard function. When we fixed the scale parameter to that of the Weibull curve with 8 year median, the maximum likelihood estimate of the levelling point was 2.7 years, and a clearly superior fit was produced compared to a pure Weibull progression with the same scale parameter (likelihood ratio chi-square of 10.6 on 1 degree of freedom, p = 0.001). The maximum was indistinguishable in fit from the levelling point of 3.5 years hypothesized in advance (chi-square = 0.30, d.f. = 1, p = 0.58). Backcalculation, however, could not determine the Weibull scale parameter itself because the likelihood was quite flat as a function of this parameter. We conclude that one must determine the parameters governing the initial shape of the hazard function from other kinds of data.(ABSTRACT TRUNCATED AT 400 WORDS)
Acquired Immunodeficiency Syndrome↗
HIV-1 and the aetiology of AIDS.
The belief that HIV-1 infection causes AIDs has been questioned, and the suggestion made that to know the correct cause of AIDS the incidence of disease in patients with and without risk behaviours and with and without antibody to HIV-1 must be known. We describe findings in such a cohort. In 715 homosexual men followed for a median of 8.6 years, all 136 AIDS cases occurred in the 365 individuals with pre-existing HIV-1 antibody. Most men negative for HIV-1 antibody reported risk behaviours but none developed any AIDS illnesses. CD4 counts fell in anti-HIV-1-positive men but remained stable in antibody-negative men, whether or not risk behaviours were present. The hypothesis that AIDS in homosexual men is caused not by HIV-1 infection but by drugs and sexual activity is rejected by these data. HIV-1 has an integral role in the pathogenesis of AIDS.
Acquired Immunodeficiency Syndrome↗
AIDS: the fictions, the facts.
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Acquired Immunodeficiency Syndrome↗
Oral corticosteroids in patients with mild Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome (AIDS).
OBJECTIVE: To assess the effect of oral corticosteroids in patients with mild Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome (AIDS). DESIGN: Prospective, double blind, placebo controlled, randomized trial. METHODS: Included were AIDS patients having their first episode of P. carinii pneumonia, who had no other known active pulmonary pathology, who had no contraindications for corticosteroids and who had received no other anti-P. carinii medications for more than 48 h. Subjects received either prednisone, 60 mg/day for 7 days, followed by a progressive tapering over 14 days, or identical placebo. The present analysis pertains to patients with mild P. carinii pneumonia as defined by a baseline resting oxygen saturation greater than 90% and a decrease in oxygen saturation during exercise while breathing room air of not less than 5 percentage points. Early deterioration, the end-point of the trial, was defined as a 10% decrease from baseline oxygen saturation on day 3 or thereafter. RESULTS: At study termination, there were 12 subjects in the placebo group and 11 in the corticosteroid group. Baseline characteristics were not statistically different between the treatment groups. Early deterioration developed in 7 and 1 patients in the placebo and corticosteroid groups respectively (P = 0.027). In addition, by day 3, a number of parameters were less favorable in the placebo group relative to the corticosteroid group including median oxygen saturation (85% vs 97%; P = 0.003), lactic dehydrogenase (1514 vs 763; P = 0.013), median respiratory rate (30 vs 22; P = 0.003), median heart rate (100 vs 81; P = 0.002), and median temperature (39 vs 37; P = 0.024). Even though patients suffering early deterioration in the placebo group were switched to corticosteroids, significant differences between the groups remained at day 30 with regard to exercise tolerance. More than half of patients assigned to the corticosteroid group exercised for a median of 6.5 min on day 30 (P = 0.017). CONCLUSION: Oral corticosteroids prevent early deterioration and increase exercise tolerance in patients with mild AIDS-related P. carinii pneumonia as defined on the basis of pulse oximetry.
AIDS-Related Opportunistic Infections↗
Clinical correlates of in vitro HIV-1 resistance ot zidovudine. Results of the Multicentre Canadian AZT Trial.
OBJECTIVE: To describe the rate of development of in vitro HIV resistance to zidovudine (ZDV) and its prognostic implications within the Multicentre Canadian AZT Trial (MCAT). METHODS: HIV-infected subjects in Centers for Disease Control (CDC) stages IIB, III and IVC-2 with CD4 cell counts > 270 x 10(6)/l were treated with ZDV as part of a dose-range study. Participating volunteers underwent prospective clinical and laboratory evaluations at regular intervals. Viral cultures and sensitivity testing were performed every 12 weeks in a predefined subset of 50 volunteers. An isolate was designated ZDV-resistant if it had a median inhibitory concentration (IC50) for ZDV at least 50-fold higher than that of virus isolated from the same subject before initiation of antiviral chemotherapy. The relationship between resistance and subsequent disease progression was studied using the Mantel and Byar method, for which, at each instance of disease progression, 2 x 2 tables classifying progression versus resistance status were constructed. The observed number of progressions was compared with that expected under the null hypothesis using Mantel-Haenszel methods adjusted for baseline CD4:CD8 ratio. RESULTS: The Kaplan-Meier estimate for the cumulative development of in vitro resistance was 64% [95% confidence interval (CI), 41-78] at 180 weeks. Baseline CD4:CD8 ratio was negatively associated (P = 0.10) with the subsequent development of resistance (proportional hazard, 0.44; 95% CI, 0.17-1.10). After adjusting for baseline CD4:CD8 ratio, the numbers of observed and expected progressions following the development of resistance were 15 and 7.6, respectively (P = 0.008). A similar relative risk of progression between resistant and non-resistant states was found in the two CD4:CD8 strata; observed and expected progressions were 4 and 2.3 and 11 and 5.2 in the high and low CD4:CD8 strata, respectively. CONCLUSIONS: In vitro resistance to ZDV developed in 64% of subjects after 180 weeks of ZDV therapy. Lower CD4:CD8 ratio at baseline was associated with faster development of resistance. In addition, the development of resistance was found to be a marker of subsequent disease progression. This association persisted after adjustment for baseline CD4:CD8 ratio. Whether in vitro resistance to ZDV is merely a surrogate marker or a determinant of disease progression remains to be established.
Adult↗
Differences in time from HIV seroconversion to CD4+ lymphocyte end-points and AIDS in cohorts of homosexual men.
OBJECTIVE: To evaluate the decline in CD4+ counts in relation to the incidence of AIDS in different cohorts of homosexual men and to quantify possible consequences of laboratory variation in CD4+ measurement. METHODS: Our study includes 403 men with well documented dates of HIV seroconversion originating from five cohort studies among homosexual men. Differences in time from HIV seroconversion to the first CD4+ count dropping < 500 or 200 x 10(6)/l and to AIDS were evaluated using Kaplan-Meier survival analyses. RESULTS: We found considerable differences between cohorts in CD4+ depletion, but not in the incidence of AIDS (1987 definition). CONCLUSIONS: Variation in CD4+ depletion appears to be mainly the result of laboratory differences. Policy recommendations on a basis of CD4+ counts probably requires a calibration of measurement. The 1993 AIDS case definition leads to a site-specific shortening of the incubation time, which complicates the study of the natural history of HIV infection and of trends in the AIDS epidemic.
Acquired Immunodeficiency Syndrome↗
Combining pooling and alternative algorithms in seroprevalence studies.
Data from two seroprevalence studies and one comparative study of confirmatory algorithms were used to compare the costs and sensitivities of six algorithms for determining seropositivity to human immunodeficiency virus (HIV). We evaluated confirmatory strategies by using the CBC Recombigen HIV enzyme immunoassay (EIA; Cambridge BioScience, Worcester, Mass.) and immunoblotting followed by radioimmunoprecipitation assay to confirm indeterminate immunoblotting results with and without pooling of samples during screening. The least expensive algorithm was that in which sera were pooled during screening and EIA was used to confirm positive test results. The cost savings associated with this confirmatory test were greater when the prevalence of HIV infection was higher. Savings from pooling of sera for screen testing diminished as HIV prevalence increased. The sensitivity and specificity of EIA with respect to immunoblotting and radioimmunoprecipitation assay were estimated to be 0.9992 and 0.9977, respectively. We found that the implementation of pooling during screening and the use of EIA as the confirmatory test do not affect the statistical reliability of estimates of seropositivity but do result in considerable cost savings.
Algorithms↗
The psychological consequences of predictive testing for Huntington's disease. Canadian Collaborative Study of Predictive Testing.
BACKGROUND: Advances in molecular genetics have led to the development of tests that can predict the risk of inheriting the genes for several adult-onset diseases. However, the psychological consequences of such testing are not well understood. METHODS: The 135 participants in the Canadian program of genetic testing to predict the risk of Huntington's disease were followed prospectively in three groups according to their test results: the increased-risk group (37 participants), the decreased-risk group (58 participants), and the group with no change in risk (the no-change group) (40 participants). All the participants received counseling before and after testing. Standard measures of psychological distress (the General Severity Index of the Symptom Check List 90-R), depression (the Beck Depression Inventory), and well-being (the General Well-Being Scale) were administered before genetic testing and again at intervals of 7 to 10 days, 6 months, and 12 months after the participants received their test results. RESULTS: At each follow-up assessment, the decreased-risk group had lower scores for distress than before testing (P < 0.001). The increased-risk group showed no significant change from base line on any follow-up measure, but over the year of study there were small linear declines (P < 0.023) for distress and depression. The no-change group had scores lower than at base line on the index of general well-being at each follow-up (P < or = 0.045). At the 12-month follow-up, both the increased-risk group and the decreased-risk group had lower scores for depression and higher scores for well-being than the no-change group (P < or = 0.049). CONCLUSIONS: Predictive testing for Huntington's disease has potential benefits for the psychological health of persons who receive results that indicate either an increase or a decrease in the risk of inheriting the gene for the disease.
Adult↗