Age at first pregnancy and risk of colorectal cancer: a case-control study.

Results from a case-control study of colorectal cancer conducted in Toronto and Calgary, Canada, are reported with respect to pregnancy-related variables. A total of 158 female "ever-married" colon cancer cases, 71 rectum cancer cases, 242 neighborhood controls, and 257 hospital controls were interviewed to obtain a complete pregnancy history. The results indicate a strong protective effect of early age at first pregnancy for both colon and rectum cancers, with little or no effect noted for the total number of pregnancies. There is a suggestion that age at first pregnancy may have a greater effect on right colon cancer than on left colon cancer. In addition, there also is a suggestion that non-live-birth outcomes may be a risk factor for both colon and rectum cancer. The similarity of these results to those of other studies on large bowel cancer and on breast cancer support the hypothesis that carcinogenesis in the large bowel may be at least partly mediated by female sex hormones.

An exploratory case-control study of brain tumors in adults.

An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies.

Determinants of short- and long-term outcome in patients with respiratory failure caused by AIDS-related Pneumocystis carinii pneumonia.

OBJECTIVES: To determine (1) predictors of in-hospital mortality and long-term survival in patients with acute respiratory failure (ARF) caused by acquired immunodeficiency syndrome-related Pneumocystis carinii pneumonia (PCP) and (2) long-term survival for patients with ARF relative to those without ARF. METHODS: A retrospective medical chart review was conducted of all cases of PCP-related ARF for which the patient was admitted to the intensive care unit of a single tertiary care institution between 1991 and 1996. Data were extracted regarding physiologic scores, relevant laboratory values, and duration of previous maximal therapy with combined anti-PCP agents and corticosteroids at entry to the intensive care unit. Duration of survival was determined by Kaplan-Meier methods from date of first hospital admission and compared for patients with and without ARF. RESULTS: There were 41 admissions to the intensive care unit among 39 patients, with 56.4% in-hospital mortality. Higher physiologic scores (Acute Physiology and Chronic Health Evaluation II [APACHE II], Acute Lung Injury, and modified Multisystem Organ Failure scores) were predictive of in-hospital mortality. Duration of previous maximal therapy also predicted in-hospital mortality (45% for patients with <5 days of previous maximal therapy vs 88% for those with > or =5 days of previous maximal therapy; P = .03). Combining physiologic scores and duration of previous maximal therapy enhanced prediction of in-hospital mortality. There was no difference in long-term survival between patients with PCP with ARF and those without ARF (P = .80), and baseline characteristics did not predict long-term survival. CONCLUSIONS: In-hospital mortality of patients with acquired immunodeficiency syndrome-related PCP and ARF is predicted by duration of previous maximal therapy and physiologic scores, and their combination enhances predictive accuracy. Long-term survival of patients with ARF caused by PCP is comparable to that of patients with PCP who do not develop ARF, and determinants of in-hospital mortality do not predict long-term survival.

Application of the World Health Organization system for HIV infection in a cohort of homosexual men in developing a prognostically meaningful staging system.

OBJECTIVE: Validation of a modified version of the recently proposed World Health Organization (WHO) staging system for HIV infection and disease in a cohort of homosexual men. METHODS: Five hundred and thirty HIV-positive men followed for a median of 51 months (range, 1-98 months) were eligible for analysis. Subjects were classified into stages at their first seropositive visit and at all subsequent visits. RESULTS: As of 1 April 1991, 136 subjects (26%) had progressed to stage IV of the modified WHO system on the basis of their CD4 lymphocyte counts, and 78 subjects (15%) had died. Kaplan-Meier estimates for progression to stage IV from stages I, II and III were 52.8 +/- 7.5% over 6.6 years, 58.1 +/- 7.1% over 5.9 years and 66.5 +/- 9.7% over 5.7 years (log-rank P = 0.0001). Estimated median times to stage IV were 6.4, 5.3 and 3.8 years from stages I, II and III, respectively. Estimated median times to death were 10.9, 8.2, 6.3 and 1.7 years from stages I to IV, respectively. Results remained unchanged when CD4 lymphocyte count was replaced with lymphocyte count in the laboratory axis of the staging system. CONCLUSIONS: The proposed staging scheme, based on the WHO system, provides a prognostically meaningful classification for HIV infection in a cohort of homosexual men. Furthermore, the use of absolute lymphocyte count as a valid alternative for CD4 lymphocyte count has implications for the applicability of this system in many parts of the world where diagnostic resources are limited.

Effects of long-term seropositivity to human immunodeficiency virus in a cohort of homosexual men.

The long-term effects of HIV infection were evaluated by comparing data from two visits a mean of 18 months apart in groups of 148 persistently seropositive and 287 persistently seronegative homosexual men. At each visit, the seropositive men exhibited lower CD4 counts, CD4/CD8 ratios, hemoglobin concentrations and lymphocyte counts, and higher C1q binding, IgG and IgA levels. More important, the decline of the CD4/CD8 ratio and the rise of the C1q binding, IgG and IgA, progressed significantly in the seropositive group between visits. Seropositive men were at elevated risk of developing constitutional symptoms and generalized lymphadenopathy. An association was present between development of symptoms and inversion of the CD4/CD8 ratio. The 11 seropositive men who have progressed to AIDS had lower CD4 counts and CD4/CD8 ratios, and higher C1q binding, IgG and IgA, than 134 seropositive AIDS-free men a mean of 21.4 months prior to diagnosis. The AIDS group demonstrated greater decline between visits in the CD4 count, hemoglobin and white blood count (WBC) than the seropositive AIDS-free group. The present data document the long-term effects of HIV infection in a seropositive cohort and suggest the possibility of a subgroup particularly susceptible to the progressive effects of HIV that precede the development of the acquired immunodeficiency syndrome (AIDS).

Comparison of sexual behaviors, unprotected sex, and substance use between two independent cohorts of gay and bisexual men.

OBJECTIVE: To compare demographic characteristics, sexual practices, unprotected receptive and insertive anal intercourse, substance use and rates of HIV-1 seroconversion between two prospective cohorts of HIV-negative men who have sex with men. DESIGN: Comparative analysis of two independent cohorts. METHODS: Between May 1995 and April 1996, 235 HIV-negative Vanguard Project (VP) participants were enrolled and between January and December 1985, 263 HIV-negative participants in the Vancouver Lymphadenopathy AIDS Study (VLAS) completed a follow-up visit. The VP participants were compared with VLAS participants with respect to self-reported demographic variables, sexual behaviors, unprotected sex, substance use and rates of HIV-1 seroconversion during follow-up. RESULTS: In comparison with the VLAS participants the VP participants were younger (median age, 26 versus 34 years; P< 0.001), more likely to be non-Caucasian (75 versus 97%; P< 0.001), and were less likely to have attended university/college (35 versus 46%; P = 0.014). The VP participants reported a higher mean number of male sex partners in the previous year (15 versus 12; P= 0.026) and a higher mean number of regular partners (1.7 versus 0.6; P < 0.001). The VP participants were more likely to report engaging in receptive (92 versus 60%; P< 0.001) and insertive (90 versus 69%; P < 0.001) anal intercourse with regular partners and receptive anal intercourse with casual partners (62 versus 38%; P< 0.001). The VLAS participants were more likely to report never using condoms during insertive and receptive anal intercourse with both regular and casual partners. The VP participants were less likely to report using nitrite inhalants (34 versus 43%; P= 0.033), but more likely to report the use of cocaine (30 versus 8%; P< 0.001), LSD (21 versus 3%; P < 0.001), amphetamine (11 versus 1%; P< 0.001), heroin (3 versus 0%; P= 0.010) and methyldiamphetamine (17 versus 10%; P= 0.034). The VLAS participants were nine times more likely to report high-risk sexual behavior, after controlling for differences in age, ethnicity, substance use, and method of recruitment between cohort members. After adjustment for differences in demographics, sexual behaviors, and level of substance use, the risk ratio for seroconversion among VLAS participants remained significantly elevated compared with VP participants. CONCLUSION: These data provide evidence that men who have sex with men who were enrolled in the VP were more sexually active than their VLAS counterparts were 10 years ago as measured by self-reported numbers of regular and casual partners and frequency of anal intercourse with these partners. However, condom use appears to be significantly higher among VP participants, which has contributed to a lower rate of HIV-1 infection.

One world, one hope: the cost of providing antiretroviral therapy to all nations.

OBJECTIVE: To estimate the potential direct cost of making triple combination antiretroviral therapy widely available to HIV-positive adults and children living in countries throughout the world. METHODS: For each country, antiretroviral costs were obtained by multiplying the annual cost of triple antiretroviral therapy by the estimated number of HIV-positive persons accessing therapy. Per capita antiretroviral costs were computed by dividing the antiretroviral costs by the country's total population. The potential economic burden was calculated by dividing per capita antiretroviral costs by the gross national product (GNP) per capita. All values are expressed in 1997 US dollars. RESULTS: The potential cost of making triple combination antiretroviral therapy available to HIV-positive individuals throughout the world was estimated to be over US$ 65.8 billion. By far the greatest financial burden was on sub-Saharan Africa. The highest per capita drug cost in this region would be incurred in the subregions of Southern Africa (US$ 149) followed by East Africa (US$ 116), Middle Africa (US$ 44), and West Africa (US$ 42). In the Americas, subregional data indicated the highest per capita drug cost would be in the Latin Caribbean (US$ 22), followed by the Caribbean (US$ 17), Andean Area (US$ 7), the Southern Cone (US$ 6), North America (US$ 6), and Central American Isthmus (US$ 5). In Asia and Europe the percentage of the GNP necessary to finance drug therapy was less than 1% in most countries examined. CONCLUSION: Our results demonstrate that the cost of making combination antiretroviral therapy available worldwide would be exceedingly high, especially in countries with limited financial resources.

PIP: In 1997, an estimated 5.8 million people worldwide were infected with HIV, of whom 90% lived in developing countries, especially in sub-Saharan Africa. While antiretroviral therapy has been shown to prolong survival in people with HIV/AIDS, many of the countries with the highest rates of HIV infection have little or no access to antiretroviral therapy, for a number of reasons, including cost. Findings are presented from a study conducted to estimate the potential direct cost of making triple combination antiretroviral therapy widely available to all of the world's HIV-infected population. The potential cost of making such therapy available to HIV-positive people worldwide was estimated to be over US$65.8 billion, in 1997 US dollars, with the greatest expenditures needed in sub-Saharan Africa. The highest per capita drug cost in sub-Saharan Africa would be incurred in Southern Africa (US$149), followed by East Africa (US$116), Middle Africa (US$44), and West Africa (US$42). In the Americas, per capita drug costs would be US$22 in the Latin Caribbean, US$17 in the Caribbean, US$7 in the Andean Area, US$6 in the Southern Cone and North America, and US$5 in the Central American Isthmus. In Europe and Asia, the percentage of GNP needed to finance drug therapy was less than 1% in most countries examined. For each country, antiviral costs were determined by multiplying the annual cost of triple antiretroviral therapy by the estimated number of HIV-positive people accessing therapy. Per capita therapy costs were calculated by dividing the antiretroviral costs by the country's total population. The potential economic burden was calculated by dividing per capita antiretroviral costs by the gross national product (GNP) per capita.

Low HIV-1 proviral DNA burden detected by negative polymerase chain reaction in seropositive individuals correlates with slower disease progression.

During 1989, 316 members of a cohort of homosexual men were tested for HIV-specific DNA by the polymerase chain reaction (PCR) using a pair of gag-region primers. Of 125 HIV-seronegative subjects, 123 (98.4%) were PCR-negative while 158 (82.7%) of 191 HIV-seropositive subjects were PCR-positive. Fewer of the 33 subjects who were seropositive and PCR-negative were at Centers for Disease Control (CDC) stage IV than the seropositive, PCR-positive subjects (6 versus 25%; P = 0.030). The seropositive, PCR-negative group had higher mean CD4 counts (640 versus 490 x 10(6) cells/l; P = 0.006), higher CD4: CD8 ratios (0.92 versus 0.64; P = 0.004), lower immunoglobulin (Ig) G levels (1290 versus 1645 mg/dl; P = 0.002), lower IgA levels (168 versus 251 mg/dl; P less than 0.001), and lower C1q binding activity (8 versus 14%; P = 0.010) than the seropositive, PCR-positive subjects. The median rate of CD4 cell decline in the 3 years preceding the PCR sample was less marked in the seropositive, PCR-negative group than the seropositive, PCR-positive group (-58 versus -77 x 10(6) cells/l per year; P = 0.028). To control for duration of infection, we restricted the analysis to the subgroups of 11 seropositive, PCR-negative subjects and 34 seropositive, PCR-positive subjects who had seroconverted earlier in the cohort study. Both subgroups had similar durations of infection, yet the same pattern of differences persisted.(ABSTRACT TRUNCATED AT 250 WORDS)

Susceptibility to AIDS progression appears early in HIV infection.

To investigate whether predictors of AIDS progression are operative very early in the natural history of HIV infection, we conducted a nested case-control study within a cohort of 119 subjects who seroconverted while under observation in a prospective study of homosexual men. For each of the 18 cases who have progressed to AIDS, we randomly selected three controls who had seroconverted within 3 months of the case but who have remained AIDS-free. Cases and controls were compared with regard to laboratory and clinical parameters obtained at the time of the earliest HIV-positive result. The median duration between the estimated date of seroconversion and this first positive result was 4 months for cases and 6 months for controls. Cases exhibited lower CD4 counts (657 versus 774 x 10(6)/l; P = 0.037), lower CD4: CD8 ratios (0.98 versus 1.39; P = 0.003), higher immune complex levels (C1q binding: 25 versus 15%; P = 0.002), lower hemaglobin concentrations (14.8 versus 15.2 g/l; P = 0.011), higher immunoglobulin (Ig) A levels (272 versus 184 mg/dl; P = 0.003), and higher IgG levels (1530 versus 1300 mg/dl; P = 0.037) than controls. Cases exhibited higher CD8 counts of marginal statistical significance (732 versus 597 x 10(6)/l; P = 0.059). No differences were observed with respect to IgM levels, total lymphocyte or white blood cell counts, or the frequency of generalized lymphadenopathy. A total of 27.8% of cases but only 11.5% of controls reported one or more symptoms during the 6-month period preceding the first positive visit (P = 0.027). We conclude that laboratory and clinical abnormalities which are predictive of more rapid progression to AIDS may appear very early in HIV infection. This suggests that some of the factors responsible for more rapid disease progression are present in the host prior to or shortly after infection occurs.

Increasing incidence of HIV infections among young gay and bisexual men in Vancouver.

Since the beginning of the HIV epidemic in north America, the majority of HIV infections have occurred among men who engage in sexual relations with other men. As the HIV epidemic enters its third decade, gay and bisexual men continue to have among the highest rates of HIV infection. Previous studies have highlighted the decline in the incidence of HIV and risk behaviour among gay and bisexual men. However, several studies have suggested that young gay and bisexual men continue to engage in unprotected sexual behaviours and are at continued risk of HIV infection. Recent reports in the media and research literature have indicated an increase in the incidence of HIV among gay and bisexual individuals in many of the world's major cities. The purpose of this study was to determine trends in HIV incidence using data from a prospective cohort of young gay and bisexual men.

Progression to AIDS and predictors of AIDS in seroprevalent and seroincident cohorts of homosexual men.

As part of an ongoing prospective study of seropositive homosexual men in Vancouver, Canada, a seroprevalent cohort of 246 subjects (i.e. duration of infection unknown) and a seroincident cohort of 102 subjects (i.e. duration of infection known) were followed a median of 63 and 45 months, respectively. Follow-up with validation utilizing record linkage with the Canadian Federal Centre for AIDS registry revealed 58 and nine cases of AIDS in the seroprevalent and seroincident cohorts, respectively, through July 1988. These data yield product limit estimates of the cumulative progression rates to AIDS at 60 months of 23.0% for the seroprevalent cohort, 13.0% for the seroincident cohort, and 21.0% for the combined groups. Univariate analyses revealed the following to be statistically and clinically significant predictors of AIDS progression: low CD4 counts, low CD4/CD8 ratios, elevated immune complexes, elevated immunoglobulin G (IgG) and immunoglobulin A (IgA) levels, and low platelet counts. Cox regression revealed that elevated IgA levels, low CD4 counts, elevated immune complexes, two or more symptoms, and more than 20 male sexual partners in high-risk areas in the 5 years prior to enrollment were independent predictors of progression to AIDS over the subsequent 5 years. A multivariate risk function based on the latter five variables delineated low-, medium- and high-risk groups whose 5-year progression rates to AIDS were 6.7, 15.6 and 64.4%, respectively. The high-risk group contained 75% of all subjects who progressed to AIDS. Only 6% of the high-risk group would have qualified for zidovudine therapy under current guidelines at the beginning of the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Evidence that prior immune dysfunction predisposes to human immunodeficiency virus infection in homosexual men.

To investigate the role of host susceptibility to HIV-1 infection, we studied subsequent seroconversion in 161 individuals, initially seronegative to HIV-1, who underwent skin testing for cutaneous anergy at an index visit within a prospective study of homosexual men. There were 23 seroconversions in these men by 45 months following the skin testing, yielding a crude rate of seroconversion of 14.3%. While results of purified protein derivative (PPD), Candida, and Trichophyton skin tests were not associated with subsequent course, anergy to dinitrochlorobenzene (DNCB) was predictive of subsequent seroconversion. Kaplan-Meier estimates for the risk of seroconversion during 45 months of follow-up in those men initially anergic and reactive to DNCB were 28.9 and 11.1%, respectively, yielding a relative risk of 2.6 (p = 0.006). The estimated relative risk was stable with adjustment by Cox regression for annual number of male sexual partners and frequency of receptive anal intercourse, and was not sensitive to various changes in the definition of seroconversion time and of eligibility criteria. These data suggest that an impaired host immune status may be associated with an increased risk of HIV-1 infection that is independent of risk of exposure to the virus, supporting earlier speculations that HIV-1 may itself be opportunistic. The notion of varying host susceptibility to infection, at least with regard to sexual transmission in homosexual men, may help to explain the frequent observation of individuals who have been repeatedly exposed to the virus and yet have remained uninfected.

Risk factors for Kaposi's sarcoma in the Vancouver Lymphadenopathy-AIDS Study.

In our ongoing cohort study of homosexual men, the ratio of new Kaposi's sarcoma (KS) cases to new opportunistic infections (OI) during the periods 1982-1985, 1986-1987, and 1988-1989 fell from 0.75 (9 KS: 12 OI) to 0.57 (12 KS:21 OI) to 0.27 (4 KS:15 OI), respectively. To examine factors associated with the development of KS as compared to OI, we compared antecedent risk factors in 25 KS cases and 48 OI "controls." In univariate analyses, several classical HIV risk factors including numbers of sexual partners and receptive anal intercourse were higher in the KS than the OI group. The strongest associations were found with an elevated number of sex partners in high-risk areas (San Francisco, Los Angeles, and New York) in the 5 years prior to enrollment and with elevated use of nitrite inhalants. Logistic regression revealed the latter two variables and an elevated number of partners contacted in washrooms/parks to be significant, independent risk factors for KS relative to OI. Any or all of these variables could be related with early HIV infection. However, the association with early sexual contact in high-risk areas raises the more intriguing possibility that this variable is an indicator of an increased exposure either to a particular strain of HIV that is more pathogenic for KS, or, more likely, to a sexually transmitted KS cofactor that may have been more highly concentrated in these areas at this early point in the epidemic. The present study supports an independent association with use of nitrite inhalants, which could be hypothesized either to have an independent biologic effect on KS or to enhance the efficiency of transmission of the cofactor virus.

Heterogeneity of physician agreement with recommended therapeutic guidelines for the management of HIV-associated disease.

The aims of this study were to assess the degree of heterogeneity in the knowledge of therapeutic management of HIV infection among HIV-experienced physicians in British Columbia, Canada, and to identify associations between physician characteristics and their agreement with contemporary therapeutic guidelines. A self-administered anonymous questionnaire was mailed to 6500 physician members of the British Columbia Medical Association. The questionnaire provided information about demographic and personal characteristics, including sex, age, medical specialization and practice location; level of experience in treating HIV-infected patients; use of HIV testing procedures; use of preventative vaccinations and tests; and preferred approaches to antiretroviral therapy and the prophylaxis and acute treatment of opportunistic infections. We compared physicians' patterns of knowledge with contemporary recommendations. Logistic regression identified associations between physician characteristics and their agreement with contemporary guidelines. A total of 463 HIV-experienced physicians (a high proportion of the HIV-experienced physicians in British Columbia, Canada) responded to the questionnaire. The agreement with contemporary guidelines about HIV testing and preventative vaccinations and tests among responders ranged from 27% to 71%. For antiretroviral therapy, agreement with the guidelines ranged from 12% to 35%. For the prophylaxis and treatment of opportunistic infections, agreement with the guidelines ranged from 11% to 89% (prophylaxis) and from 46% to 91% (treatment). Regression analysis revealed that physicians actively involved in the care of HIV-infected patients were more likely to agree with the guidelines in all areas of patient care. General practitioners were more likely to agree with the guidelines regarding preventative therapies, and male general practitioners under 45 years old were more likely to agree with the guidelines on antiretroviral therapy. Our data confirm that there is substantial heterogeneity in the management of HIV-associated disease, including some deviations from contemporary guidelines. Concordance with contemporary guidelines increased with the physician's level of HIV-related experience. Our results support the idea that adherence to state-of-the-art practices may be responsible, at least in part, for the recently described association between physician experience and improved survival of HIV-infected individuals.

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)

Modelling the impact of HIV disease on mortality in gay and bisexual men.

OBJECTIVE: To assess how HIV infection and AIDS (HIV/AIDS) impacts on mortality rates for gay and bisexual men. METHODS: Vital statistics data were obtained for a large Canadian urban centre from 1987 to 1992. Three scenarios were utilized with assumed proportions of gay and bisexual men of 3%, 6% and 9% among the male population age 20 years. For each scenario, non-HIV deaths were distributed according to the assumed proportion of the total population (3%, 6% or 9%) but 95% of HIV deaths were distributed to gay and bisexual men as this is the proportion of AIDS cases in gay and bisexual men in this centre. The main outcome measures of interest were age-specific patterns of death, life expectancy and life expectancy lost due to HIV/AIDS at exact age 20 years, and the probability of living from age 20 to 65 years. RESULTS: Estimates of the mid-period gay and bisexual population ranged from 5406 to 16,219 for the three scenarios, and total deaths in these men from 953 to 1703. Age-specific mortality was significantly higher for gay and bisexual men than all men aged 30-44. Life expectancy at age 20 for gay and bisexual men ranged from 34.0 years to 46.3 years for the 3% and 9% scenarios respectively. These were all lower than the 54.3 year life expectancy at age 20 for all men. The probability of living from age 20 to 65 years for gay and bisexual men ranged from 32% for the 3% scenario, to 59% for the 9% scenario. These figures were considerably lower than for all men where the probability of living from 20 to 65 was 78%. CONCLUSION: In a major Canadian centre, life expectancy at age 20 years for gay and bisexual men is 8 to 20 years less than for all men. If the same pattern of mortality were to continue, we estimate that nearly half of gay and bisexual men currently aged 20 years will not reach their 65th birthday. Under even the most liberal assumptions, gay and bisexual men in this urban centre are now experiencing a life expectancy similar to that experienced by all men in Canada in the year 1871.

Secular trends in the survival of HIV-infected homosexual men in Amsterdam and Vancouver estimated from a death-included CD4-staged Markov model.

BACKGROUND: The purpose of this study was to investigate secular trends in waiting times in CD4-based stages of human immunodeficiency virus (HIV) disease progression in two cohorts of homosexual men, one in Vancouver and one in Amsterdam. All HIV-positive men with two or more CD4 counts in their AIDS-free period between 1 January 1985 and 1 January 1997 were included in this study. Data regarding clinical AIDS diagnoses (using the 1987 Centers for Disease Control and Prevention [CDC] AIDS case definition) and death were collected through active follow-up, review of hospital records, and municipal/national registries. The Vancouver Lymphadenopathy-AIDS Study (VLAS), was started in November 1982 and had enrollment until December 1984. Both HIV-negative and HIV-positive men were followed at intervals of 3-6 months until 1986 and annually thereafter. The Amsterdam cohort study on HIV and AIDS (ACS) started in December 1984, has ongoing enrollment and follow-up of both HIV-negative and HIV-positive homosexual men. The HIV-positive men were followed at intervals of 3 months. METHODS: The CD4-based stage of an individual at each visit was determined using smoothed data. For each cohort and in each calendar time period, a CD4-based Markov model with death as the absorbing stage was fitted to the data. The parameters in this model were estimated using the method of maximum likelihood and confidence intervals were calculated using bootstrap methods. RESULTS: A total of 509 homosexual men participating in the VLAS were included in this study, providing 5356 visits. Some 292 men developed AIDS before 1 January 1997 and 239 died before this date. In all, 232 of the 239 deaths were AIDS related. Thirty-seven per cent of all visits were related to treatment. A total of 543 homosexual men participating in the ACS were included in this study, providing 10 043 visits; 277 men developed AIDS before 1 January 1997 and 250 died before this date. The date of AIDS diagnosis was known for 225 of the 250 deaths. Twenty per cent of all visits were related to treatment. We found that in both cohort studies the stage-specific waiting times were longer in the low CD4-based stages (stages 4, 5 and 6: i.e. CD4 count <500 cells per mm(3)) after March 1990 compared to waiting times before March 1990. The increase in mean waiting time in these stages with low CD4 count was 21%, 33% and 53%, respectively in the ACS and 20%, 2% and 29% in the VLAS. Because waiting times alone are not exclusive for progression in a reversible model we also calculated the stage-specific median incubation periods till death. Men spent considerably longer in these CD4-based stages after March 1990 compared to before March 1990. CONCLUSIONS: Data from these population-based cohort studies showed that HIV disease progression in the calendar period where treatment was administered was slower for individuals in stages with low CD4 counts. We found no evidence for shortening of the incubation period that may have appeared from increasing virulence of the HIV in the population.

Sex trade involvement and rates of human immunodeficiency virus positivity among young gay and bisexual men.

BACKGROUND: Susceptibility to human immunodeficiency virus (HIV) infection is of particular concern for marginalized populations. The objective of this study was to determine risk factors associated with sex trade work among young gay and bisexual men. Further, we aimed to compare HIV prevalence and incidence among men involved and not involved in sex trade work. METHODS: The study is based upon data obtained from a prospective cohort study of young gay and bisexual men. Participants had completed a baseline questionnaire which elicited information on demographic information, sexual behaviours, and substance use. Sex trade involvement was defined as the exchange of money, drugs, goods, clothing, shelter or protection for sex within the one year prior to enrollment. Contingency table and multivariate logistic regression analyses were used to identify risk factors associated with involvement in the sex trade. RESULTS: Of the 761 eligible participants, 126 (16%) reported involvement in sex trade work. Multivariate logistic regression analysis revealed regular alcohol use (Odds Ratio [OR] = 3.6, 95% CI : 1.8-7.2), aboriginal ethnicity (OR = 3.7, 95% CI : 1.6-8.7), unemployment (OR = 3.9, 95% CI : 2.1-7.3), history of residence in a psychiatric ward (OR = 4.2, 95% CI : 1.8-9.8), bisexual activity (OR = 7.0, 95% CI : 3.5-14.1) and the use of crack (OR = 7.4, 95% CI : 3.0-18.7) to be independently associated with sex trade work. Sex trade workers had a significantly higher HIV prevalence at baseline compared with non-sex trade workers (7.3% versus 1.1%, P < 0.001). As well, HIV incidence was found to be significantly higher for sex trade workers compared with non-sex trade workers (4.7% versus 0.9%, P = 0.011). CONCLUSION: Our study reveals that for male sex trade workers in this setting increased vulnerability to HIV infection is related to unfavourable living conditions, substance use and sexual risk behaviour.

The cost effectiveness of antiretroviral regimens for the treatment of HIV/AIDS.

OBJECTIVE: To estimate survival, the number of life-years gained and cost effectiveness of antiretroviral therapy (ART) regimens, denoted as ERA-I [zidovudine + (didanosine or zalcitabine)]; ERA-II [stavudine + (didanosine or zalcitabine) or lamivudine + (zidovudine or didanosine or zalcitabine or stavudine)]; and ERA-III [2 nucleoside reverse transcriptase inhibitors + (1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor)]. DESIGN: Modelling of drug cost, cost of opportunistic diseases and survival of HIV positive men and women in the province of British Columbia who were first prescribed any ART between October 1992 and June 1996. A 'reference cohort' was modelled upon individuals in a longitudinal cohort of homosexual men followed since 1982. PERSPECTIVE AND SETTING: Third-party payer perspective in British Columbia, Canada. PATIENTS: All HIV-positive men and women aged > or =18 years with CD4+ counts < or =350 cells/microL who were enrolled in the province-wide drug treatment programme. MAIN OUTCOME MEASURES: Annual costs, survival and cost-effectiveness ratios of successive ART regimens. RESULTS: Total costs [1997 Canadian dollars ($Can)] at 12 months under ERA-I, -II and -III were $Can4897, $Can6620 and $Can 11 914, respectively. Survival at 12 months under ERA-I, -II and -III was 89.6%, 91.0% and 97.6%, respectively. The annual incremental cost (estimated by the total incremental cost at 12 months) between ERA-II and ERA-I was $Can1723. The incremental cost-effectiveness ratios between ERA-III and ERA-I, and between ERA-III and ERA-II were $Can58 806 and $Can46 971 per life-year gained, respectively. CONCLUSION: We found the cost effectiveness of ERA-III ART regimens well within the range of currently funded therapies for the treatment of other chronic diseases.