Search PubMed⌕ Search

Biomedical subjects

M T Schechter

Publications and source records attributed to M T Schechter.

At least 109 records · Page 6Linked to original sources

A decade of research on the natural history of HIV infection: Part 1. Markers.

Within the context of HIV disease, a marker may be described as a consequence of disease that varies over time but does not necessarily predict future disease course. To date, the most powerful marker of HIV disease progression is the CD4 cell count. Other immunologic markers include neopterin, beta 2-microglobulin, and total and HIV-specific immunoglobulin levels. Further research, which focuses on cell-mediated factors such as interleukins, tumour necrosis factor, natural killer cell activity and apoptosis, is required. Measures of viral burden, such as p24 antigenemia and proviral DNA or RNA, may also offer additional prognostic information. As methods involving quantitative polymerase chain reaction become more refined, it is hoped that they may soon be applied to the clinical setting. Clinical markers of interest include the appearance of minor opportunistic infections and the occurrence of acute retroviral syndrome, which may indicate a faster disease course. Although population-based studies have identified a number of HIV disease markers, further research is required to generalize these findings to the individual level.

AIDS-Related Opportunistic Infections↗

A decade of research on the natural history of HIV infection: Part 2. Cofactors.

Cofactors of HIV disease may be considered risk modifiers that are causally related to future disease course. The search for potential cofactors, of viral, host or environmental origin, may provide avenues for altering the natural history of HIV infection. Potential viral cofactors include viral strains, such as syncytium-inducing and nonsyncytium-inducing variants, and strains that are resistant to specific antiretroviral therapies. Although there is strong evidence that sexually transmitted diseases that lead to genital ulcers or abrasions are important cofactors of HIV transmission, their role as cofactors in HIV disease progression is less clear. Further study of agents such as human herpesviruses 6 and 8 and hepatitis C may shed light on the role of other infectious agents in progressive HIV disease. Far less research has been conducted on behavioural, genetic and sociodemographic factors that may influence HIV disease progression rates. Since current anti-HIV therapies do not offer a cure, but only a means of prolonging life, the identification of possible cofactors is critical.

Comorbidity↗

HIV/AIDS mortality in Canada: evidence of gender, regional and local area differentials.

OBJECTIVE: To assess the impact of HIV infection and AIDS on mortality patterns in Canada with specific reference to gender and regional differentials and to other leading causes of death. DESIGN: Descriptive, population-based study. SETTING: Canada. PATIENTS: All persons for whom HIV/AIDS [ninth revision of the International Classification of Diseases (ICD-9) 042-044] was recorded as the underlying cause of death as reported to Statistics Canada between 1987 and 1992. For comparative purposes data was obtained on five other leading underlying causes of death including coronary heart disease (ICD-9 410-414), motor vehicle accidents (ICD-9 E810-E819), and suicides (ICD-9 E950-E959) in men and women, lung cancer (ICD-9 162) in men and breast cancer (ICD-9 174) in women. Population figures were obtained from Statistics Canada estimates. MAIN OUTCOME MEASURES: Age and cause-specific mortality rates, standardized mortality ratios (SMR), potential years of life lost (PYLL) before age 65 years, and life expectancy lost due to a select underlying cause of death. RESULTS: Over the period 1 January 1987 to 31 December 1992, 5546 deaths attributed to HIV/AIDS (5229 in men and 317 in women) were recorded in Canada. SMR for men were significantly higher than the national average in the cities of Vancouver, Toronto and Montreal, whereas those for women were significantly greater only in Montreal. Deaths from HIV/AIDS accounted for 3.6% of PYLL in men and 0.4% of PYLL in women. In 1992, HIV/AIDS was the third leading cause of male PYLL surpassing lung cancer. In the cities of Montreal, Toronto, and Vancouver HIV/AIDS was the leading cause of PYLL and was responsible for significant decrease in life expectancy at birth in men over the study period. CONCLUSIONS: HIV/AIDS has had considerable impact on mortality within Canada, principally among men and particularly in the cities of Toronto, Vancouver and Montreal.

Acquired Immunodeficiency Syndrome↗

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↗

Analysis of nutritional intake in a cohort of homosexual men.

The objective of this study was to examine differences in the nutritional intake of seronegative (SN) and seropositive (SP) AIDS-free subjects within a cohort of gay men. The nutritional intake of 145 SN and 139 SP subjects between October 1991 and September 1992 was evaluated using a self-administered 24-h dietary recall questionnaire. The calorie and nutrient content of all food items eaten in a day was coded using the Canadian Nutrient File database. SP subjects were estimated to have been HIV positive a median of 8 years (range, 0.5-9.8 years) and were AIDS-free as of November 1992. SP subjects were younger (median 38 versus 41 years; p = 0.009) and had lower body mass index (BMI) (median index 23.5 versus 24.5; p = 0.017). No significant differences was observed between the two serologic groups in regard to weight change over the previous year. Total caloric intake was significantly higher in the SP group (median, 2,198 versus 1,971 kcal; p = 0.019). SP subjects had higher intakes than SN subjects of protein (median, 94 versus 81 g; p = 0.011), fat (median, 79 versus 66 g; p = 0.023), carbohydrates (median, 240 versus 216 g, p = 0.032), and cholesterol (median 317 versus 252 mg; p = 0.017). These differences persisted after adjustment for age and BMI. In the SP group, there was no difference in caloric intake between those with CD4 counts above and below 200. HIV-infected individuals appear to have a caloric intake higher than that of HIV-negative homosexual controls from the same cohort.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Use of the Markov model to estimate the waiting times in a modified WHO staging system for HIV infection.

Seroconverting men in the Vancouver Lymphadenopathy--Acquired Immune Deficiency Syndrome Study cohort were studied in this analysis to estimate the waiting times in the different stages of the modified World Health Organization (WHO) staging system for human immunodeficiency virus infection. A time-homogeneous staged Markov model was used, and it was assumed that infected individuals progress irreversibly from Stages I to IV and eventually to death. There were 130 individuals who seroconverted during the study (seroincident) and were included in this analysis. With use of the modified WHO staging system, the estimated mean waiting times for progression to Stage IV were 9.5, 6.5, and 2.0 years from stages I, II, and III, respectively. The estimated survival times were 11.2, 8.2, 3.7, and 1.7 years from Stages I to IV, respectively. Waiting times and survival were not significantly different when the lymphocyte count was used instead of the CD4 cell count in application of the staging system. The application of a staged Markov model to the modified WHO staging system suggests that this is a clinically sensible model. Furthermore, our results confirm that in the absence of CD4 cell counts, lymphocyte counts can be used as an alternative without substantial loss of information.

Adult↗

Access to health care and geographic mobility of HIV/AIDS patients.

OBJECTIVE: To determine the patterns and determinants of mobility in persons with HIV infection or AIDS on a population basis. DESIGN: Descriptive cross-sectional population health study. TARGET POPULATION: 650 full members (i.e., HIV-positive) of the Vancouver Persons with AIDS Society who were residents of British Columbia and who allow the society to include unsolicited material with their monthly newsletter. MAIN OUTCOME MEASURES: Migration history, access to HIV-related care at diagnosis, current and pre-HIV sociodemographic characteristics, and current health status. RESULTS: Two hundred and fifty-two persons living with HIV/AIDS participated in the study. At the time of the survey, the majority of subjects were male (94 percent), aged between 30 and 54 years (87 percent), and able to carry out daily activities without assistance (84 percent). The median time since the known date of HIV infection was 6 years. Access to care at diagnosis was associated in this population with being diagnosed in the largest metropolitan area in the province (OR = 2.14; 95 percent CI: 1.18, 3.87), a pre-HIV income of $30,000 or more per annum (OR = 0.49; 95 percent CI: 0.27, 0.89), a known date of diagnosis prior to 1990 (78 percent versus 64 percent; p = 0.019), and living in the same residence from the date of known HIV diagnosis to the date of the survey (63 percent versus 51 percent; p = 0.024). CONCLUSION: Although no definitive causal association can be provided by this cross-sectional analysis, our results clearly highlight several ways in which the need for treatment and care potentially affect where persons with HIV/AIDS choose to live.

Adult↗

Is the human immunodeficiency virus-related Kaposi's sarcoma epidemic coming to an end? Insights from the Tricontinental Seroconverter Study.

A decline in the proportion of Kaposi's sarcoma among AIDS cases since the 1980s has been attributed to changes in sexual behavior among homosexual men and a decreasing exposure to a hypothesized Kaposi's sarcoma cofactor. Recent studies have shown that the incidence rate of Kaposi's sarcoma has remained relatively stable, which seems to argue against the hypothesis of a declining exposure to the putative cofactor. To examine this paradox, we evaluated the incidence of Kaposi's sarcoma, using Cox proportional hazard analyses, and performed a simulation to compare incidences of different AIDS outcomes among 407 homosexual men with documented dates of seroconversion. Our data show that men who seroconverted early in the epidemic did not progress faster to Kaposi's sarcoma than men who seroconverted more recently. A lower incidence rate of Kaposi's sarcoma would be expected among the latter group if exposure to the hypothesized cofactor is decreasing over time. The percentage of Kaposi's sarcoma among incident AIDS cases decreased over the years following seroconversion, but not over calendar time. This study demonstrates that the decline in the proportion of Kaposi's sarcoma among AIDS cases should not be interpreted as a decline in the incidence of Kaposi's sarcoma and that there is no evidence that a hypothesized Kaposi's sarcoma cofactor is declining over calendar time.

Acquired Immunodeficiency Syndrome↗

Use of pooling and outpatient laboratory specimens in an anonymous seroprevalence survey of HIV infection in British Columbia, Canada.

OBJECTIVE: To conduct an anonymous HIV seroprevalence survey to establish a baseline estimate of HIV seroprevalence in a general population; to evaluate serum pooling and alternative testing strategies as cost-saving measures. DESIGN: Prospective anonymous HIV seroprevalence study using outpatient laboratory specimens. SETTING: Two large non-hospital-associated outpatient chemistry testing laboratories in the major population centers in British Columbia, Canada. PATIENTS AND SERA: Leftover sera received for chemistry screen testing in outpatient laboratories were provided to the study after chemistry testing was completed. Those from patients aged < 15 and > or = 55 years were excluded. METHODS: Patient identifiers were erased from samples. Sera were pooled 10:1 and tested by viral lysate enzyme-linked immunosorbent assay (ELISA). Sera from HIV-positive pools were tested individually. All individual HIV-positive specimens were retested for verification of positivity using a recombinant protein ELISA. MAIN OUTCOME MEASURES: HIV seroprevalence rates were stratified by sex, age group, and geographic area; and costs of pooling and alternative algorithm strategy were compared with those of conventional methods. RESULTS: A total of 80,238 sera were collected from 66,658 individuals (53% women, 47% men). Of these, 276 men (88.3 per 10,000) and 24 women (6.8 per 10,000) were HIV-seropositive. The highest rates were in those aged 30-34 years, for both men and women. Using pooling and non-Western blot verification saved US$2.07 per specimen, or 80% of the cost for conventional testing. CONCLUSIONS: The anonymous outpatient laboratory setting is practicable to obtain a reasonable estimate of HIV seroprevalence rates in a general population. Such studies can be made cost-effective by pooling sera and using alternative confirmatory strategies.

AIDS Serodiagnosis↗

Rectal gonorrhoea as an independent risk factor for HIV infection in a cohort of homosexual men.

OBJECTIVE: To determine whether certain sexually transmitted diseases are independent risk factors for HIV transmission in a cohort of homosexual men. METHODS: Eligible cases were identified as those who had seroconverted between November 1982 and November 1990. Two persistently HIV-seronegative control participants were randomly selected for each case from all participants who remained seronegative in November 1990. For cases, risk factor data were taken from an index visit which was defined as the first seropositive visit, while for controls these data were obtained from a matched visit which occurred within two months of the index visit for the corresponding case. Mantel-Haenszel methods and logistic regression were used to compare differences in risk factors for seroconversion between cases and controls. RESULTS: A total of 125 cases and 250 controls were eligible for this study. Cases were significantly more likely to have had reported any gonorrhoea (17% versus 6%; OR = 2.94; 95% CI: 1.51-5.73) or syphilis (7% versus 2%; OR = 3.78; 95% CI: 1.33-10.79) than controls during the seroconversion period. Multivariate logistic regression revealed rectal gonorrhoea to be independently associated with risk of seroconversion (odds ratio = 3.18; p = 0.044), whereas urethral gonorrhoea (p = 0.479) and pharyngeal gonorrhoea (p = 0.434) were not after inclusion of rectal gonorrhoea. In addition, the following variables were also shown to exert an independent effect on seroconversion: frequency of anal intercourse, use of illicit drugs, number of male sexual partners, and lack of a post-secondary education. CONCLUSIONS: In this observational study, rectal gonorrhoea was found to be associated with HIV seroconversion after adjustment for a number of HIV risk factors. We cannot rule out that rectal gonorrhoea was not directly associated with HIV infection but rather with other residual lifestyle factors not fully adjusted for in the analysis. However, the relationship with gonococcal involvement of a specific anatomic site lends support to a biological association between gonorrhoea and HIV infection, rather than to alternative non-biologic explanations. Our findings are consistent with previous studies reporting an association between HIV infection and non-ulcerative sexually transmitted diseases. Such a direct association might be explained by postulating that gonorrhoea results in inflamed rectal mucosa and compromised epithelial integrity, thereby predisposing an individual to subsequent HIV infection.

Adult↗

Quantification of the variation due to laboratory and physiologic sources in CD4 lymphocyte counts of clinically stable HIV-infected individuals.

We have conducted a study to quantify the amount of variation in the CD4 lymphocyte counts of HIV-infected individuals due to laboratory and physiological factors. Thirty HIV-infected male volunteers had blood drawn on six occasions: three times in each of 2 weeks, 4 weeks apart. Two tubes of blood were drawn at each visit, and duplicate measurements were obtained from one of the tubes of blood. Differences between duplicate measurements from a single tube of blood and between CD4 counts obtained from two tubes of blood drawn on the same day were attributed to laboratory factors. Differences between CD4 counts obtained on different days were attributed to a combination of laboratory factors and physiologic factors, which included the effects of exercise, tobacco, and the consumption of alcohol and caffeine. The mean absolute CD4 count at the first visit was 450 (range 86-1,081). The short-term coefficient of variation of CD4 count was 13.7 (95% CI: 12.9, 14.6). Physiologic and laboratory factors accounted for 85% and 15% of the variation in CD4 counts, respectively. Variation in the absolute white blood cell count, lymphocyte percentage, and CD4 percentage accounted fo 52%, 29%, and 19% of the physiologic variation in CD4 counts, respectively. Our results confirm a high degree of short-term variability of CD4 counts among HIV-infected individuals, which can be largely attributed to physiological factors. This variability can be minimized more effectively by repeating CD4 counts over time than by repeating measurements at a single visit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lower socioeconomic status and shorter survival following HIV infection.

We studied the association between socioeconomic status and survival in a prospective study of 364 HIV-infected homosexual men who were recruited during 1982-84. The participants were divided by annual income; those earning above Canadian $10,000 (high-income; n = 274) and those below $10,000 (low-income; n = 90) at recruitment. The latter threshold closely approximated to the poverty level for this population. Low income men were significantly younger than high income men but the groups were similar with respect to baseline CD4 counts, subsequent use of anti-retrovirals and prophylaxis against Pneumocystis carinii pneumonia (PCP), and number of visits attended during follow-up. Subjects were followed for a median of 9.5 years (range 1.8-13.1). By Dec 31, 1993, there were 135 deaths yielding a cumulative mortality rate of mean 45% (SD 4.0) at 11.5 years. Men aged 30 or more at infection had poorer survival than those under 30 (mortality risk ratio 1.56; 95% CI 1.09-2.24; p = 0.015), and longer survival was significantly associated with a higher CD4 count at the earliest seropositive visit. The age-adjusted mortality risk ratio for low income men compared with high income men was significantly increased at 1.63 (95% CI 1.11-2.40; p = 0.013). The significant risk of death for low income men persisted despite adjustment for age at infection, CD4 count, use of zidovudine, dideoxyinosine, and dideoxycytidine, use of PCP prophylaxis, and year of infection. We cannot attribute our findings to income loss as a result of more rapid HIV progression because the same effect was present in people who provided income data before seroconversion. Similarly, our findings are not due to differential access to care because the study was done within the context of a universal health care system, and the two income groups received treatments equally. This finding is consistent with the association of lower socioeconomic status with increased morbidity and mortality observed within large populations and in other diseases.

Acquired Immunodeficiency Syndrome↗

Determinants of HIV disease progression among homosexual men registered in the Tricontinental Seroconverter Study.

Data on 403 homosexual/bisexual men with documented dates of human immunodeficiency virus (HIV) seroconversion were merged. All subjects originated from cohort studies that started between 1982 and 1984 in Amsterdam, The Netherlands; San Francisco, California; Sydney, Australia; and Vancouver, British Columbia, Canada. With respect to the four geographic locations, no statistically significant differences in progression time from HIV seroconversion to acquired immunodeficiency syndrome (AIDS) and death as well as in AIDS diagnoses patterns could be demonstrated. The median time from HIV seroconversion to AIDS was 8.3 years, that from HIV seroconversion to death was 8.9 years, and that from AIDS to death was 17 months. The authors evaluated HIV disease progression with respect to demographic, clinical, and behavioral cofactors. Younger age and use of prophylaxis against Pneumocystis carinii pneumonia were significantly related to slower progression from seroconversion to death. In addition, an association between slower progression and earlier dates of seroconversion was found. No relation of sexual behavior; history of sexually transmitted diseases; or use of alcohol, tobacco, and recreational drugs with rates of disease progression could be demonstrated.

AIDS Serodiagnosis↗

Prevalence of HIV infection in provincial prisons in British Columbia.

OBJECTIVE: To ascertain the prevalence of HIV infection among people entering provincial adult prisons in British Columbia and to study associations between HIV infection and specific demographic and behavioural characteristics. DESIGN: Prospective, unlinked, voluntary survey involving HIV antibody testing of saliva specimens. SETTING: All adult provincial prisons in British Columbia through which inmates are admitted to the provincial correctional system. PARTICIPANTS: All adult inmates admitted to provincial prisons in British Columbia between Oct. 1 and Dec. 31, 1992. OUTCOME MEASURES: Rate of HIV positivity. Independent variables included sex, native status (native or non-native), self-reported HIV status, age group and history of injection drug use. RESULTS: A total of 2482 (91.3%) of 2719 eligible inmates volunteered for testing. Refusal was not associated with sex, native status, self-reported HIV status or age group; inmates who reported a history of injection drug use were more likely than the others to refuse HIV antibody testing (12.9% v. 6.8%; p < 0.001). The 2482 inmates who were tested for HIV were similar to the general inmate population with regard to sex, native status and age group. A total of 28 inmates were confirmed to be HIV positive, for an overall prevalence rate in the study population of 1.1% (95% confidence interval 0.8% to 1.6%). The prevalence rates were higher among the women than among the men (3.3% v. 1.0%; p = 0.023, Fisher's exact test) and among the inmates who reported a history of injection drug use than among those who did not report such a history (2.4% v. 0.6%; p < 0.001). There was no association between HIV status and native status or age group. Logistic regression analysis revealed the higher prevalence rate among the women to be explained by more of the women than of the men reporting a history of injection drug use. Of the 30 people who stated that they were HIV positive and who were tested, 19 (63.3%) had a negative result; conversely, 17 who reported that they were HIV negative or had not been tested had a positive result. CONCLUSIONS: Unlinked, voluntary HIV antibody testing of inmates can achieve high participation rates. The overall prevalence rate of 1.1% and the rate among the female inmates of 3.3% confirm that HIV infection is a reality in prisons and that the virus has established a clear foothold in inmate populations. Harm-reduction interventions should include a comprehensive education program for inmates on infectious diseases, the availability of condoms throughout prisons and the distribution of bleach for sterilizing needles and syringes. From a public health perspective, these data suggest an urgent need for access to sterile injection equipment in addition to other preventive measures.

AIDS Serodiagnosis↗