Kevin J. P. Craib

Decline in deaths from AIDS due to new antiretrovirals

We determined whether availability of new antiretroviral treatments has had any impact on the rate of death for people with HIV-1 infection. Distribution of antiretroviral drugs in British Columbia, Canada, is free of charge through the Centre for Excellence in HIV/AIDS Treatment Programme. For physicians to prescribe antiretrovirals, they must complete a participant enrolment form that serves as the drug prescription. Individuals infected with HIV-1 are eligible to receive antiretroviral therapy from this programme if they have at least one CD4 cell count less than 0·5 10/L. Until December, 1995, monotherapy was made available to participants with CD4 counts less than 0·5 10/L, while double combination therapy was made available to those with CD4 counts of less than 0·35 10/L. After December, 1995, double combination treatment was made available to everyone with CD4 counts less than 0·5 10/L. Viral-loaddriven antiretroviral treatment and triple combination therapy became available after June, 1996. Of the five new medications introduced in 1996, lamivudine became available in January, saquinavir in June, stavudine in July, and indinavir and ritonavir in September. Patterns of mortality were assessed by comparing changes in death rates for those individuals on antiretroviral therapy by quarter and CD4-count groupings (0·1 10/L, 0·1–0·34 10/L, and 0·35–0·49 10/L). Mortality data were obtained through regular surveillance and computerised record linkages with Division of Vital Statistics of the British Columbia Ministry of Health. Population figures were based on the number of programme participants actively on antiretroviral therapy. Rates were expressed as deaths per 1000 active participants and were calculated over a 3-year period from January, 1994 to December, 1996. There were 604 deaths during this period among individuals ever on antiretroviral therapy; of these, 475 deaths (79%) were attributed to participants with CD4 counts less than 0·1 10/L. There was a significant decline in programme mortality rates since the first quarter of 1994 (trend test p<0·001). On average, the rate of death for those on antiretroviral treatment declined at a rate of 1·7 deaths per 1000 participants per quarter or from 18·9 deaths per 1000 participants in the first quarter of 1994 to 5·7 deaths per 1000 participants in the last quarter of 1996. As shown in the figure, the greatest decline in mortality was experienced in those participants with CD4 counts less than 0·1 10/L (trend test p<0·001). On average, the death rate for participants with CD4 counts of less than 0·1 10/L declined at a rate of 3·5 deaths per 1000 participants per quarter—ie, from 62·0 to 19·8 deaths per 1000 participants from the first quarter of 1994 to the last quarter of 1996. Although there was a decline in the death rates for other two CD4-count groups, the rates were not statistically significant. Delayed reporting was not likely to affect our analysis. The vast majority of deaths were reported through active follow-up. In this analysis, data on 536 (89%) deaths were obtained through physician and hospital reports and data on 68 (11%) were obtained through linkages. Furthermore, in a subanalysis of 179 deaths obtained through physician and hospital reports over a 1-year period ending on June 30, 1996, we found that the median follow-up time between the actual date of death and the date of reporting was 7 days (interquartile range 5–11 days). Our data show a substantial decrease in AIDS-related mortality in the province of British Columbia. The decline in mortality coincides with the availability of lamivudine in the province through open access and with the expanded use of double combination antiretroviral therapy. We believe this mortality trend will likely continue as protease inhibitors and non-nucleoside reverse transcriptase inhibitors are used to greater extent within the treatment programme.

Determinants of sexual risk-taking among young HIV-negative gay and bisexual men.

Data from a cohort of young HIV-negative gay and bisexual men were analyzed to identify determinants of sexual risk-taking at baseline. Gay/bisexual men aged between 18 and 30 completed a self-administered questionnaire including demographics, depression, social support, substance use, and consensual versus nonconsensual sex. Risk-takers were defined as those who had unprotected anal sex with casual male sex partners in the previous year; non-risk-takers were defined as those who reported consistent condom use during anal sex with all male partners in the previous year. Logistic regression was used to identify independent predictors of sexual risk-taking. Of 439 men studied, risk-takers had less education, a higher depression score, less social support, and were more likely to report nonconsensual sex and recreational drug use relative to non-risk-takers. Independent predictors of sexual risk-taking were low education, nitrite use, low social support (adjusted odds ratio [AOR]=1.65; 95% CI, 1.04-2.59), and nonconsensual sex experienced as a youth or adult (AOR=1.85; 95% CI, 1.15-2.96). Young gay/bisexual men reporting nonconsensual sex, low social support, or nitrite use were significantly more likely to have recently had unprotected anal sex with casual partners. HIV prevention programs aimed at young gay/bisexual men should include sexual abuse counselling and foster community norms supporting safer sex practices.

Impact of HIV infection on mortality in a cohort of injection drug users.

&NA; The prevalence of HIV has been rising among injection drug users (IDUs) and AIDS is now an important cause of death among that population. We tracked mortality and recorded detailed causes of death in the Vancouver Injection Drug Users Study (VIDUS). This is an open cohort of over 1,400 active IDUs that began in May 1996. At enrollment and at semiannual follow‐up visits, a trained interviewer administers a detailed semistructured questionnaire. Mortality was recorded during follow‐up and detailed causes of death were collected from coroners reports, hospital records, and the provincial (British Columbia) registry. Causes of death were obtained on 125 participants. Overall, the leading cause of death was overdose accounting for 25% of deaths among HIV‐positive participants and 42% among HIV‐negative participants. Of the 65 deaths among HIV‐positive individuals, 22 (34%) were HIV related. Mortality was associated with older age (adjusted hazards ratio [AHR], 1.03 per year), HIV positivity (AHR, 2.67), injection cocaine use (AHR, 2.23) and methadone treatment (AHR, 0.47). The high rate of HIV in this population has added significantly to the burden of illness and death in this marginalized population.

Determinants of HIV seroconversion in drug users during a period of rising prevalence in Vancouver

To identify determinants of HIV seroconversion among injection drug users (IDUs) during a period of rising prevalence, a case-control investigation was conducted. Cases were IDUs with a new positive test after 1 January 1994, and a negative test within the prior 18 months. Controls required 2 negative tests during the same period. Subjects completed a questionnaire on demographic, psychosocial, and behavioural factors. Eighty-nine cases and 192 controls were similar with respect to gender, age, ethnicity and inter-test interval. Multivariate analyses of events during the inter-test interval showed borrowing syringes (adj. OR=2.96; P 0.006), unstable housing (adj. OR=2.01; P =0.03) and injecting 4 times daily (adj. OR=1.71; P =0.06) to be independently associated with seroconversion. Protective associations were demonstrated for sex with opposite gender (adj. OR=0.36; P =0.001) and tetrahydrocannabinol use (adj. OR=0.41; P =0.001). There is a need to evaluate programmes dealing with addiction, housing and the social underpinnings of risk behaviours in this population. <

Surviving the sex trade: a comparison of HIV risk behaviours among street-involved women in two Canadian cities who inject drugs.

In Canada, very little is known about the factors and processes that cause drug-related harm among female intravenous drug users (IDUs). Women who inject drugs and participate in the survival sex trade are considered to be at increased risk for sexual and drug-related harms, including HIV infection. Between September 1999 and September 2000, women participating in the VIDUS cohort in Vancouver and the St. Luc Cohort in Montreal completed interviewer-administered questionnaires. Analyses were conducted to compare the demographic characteristics, sexual risk behaviours, risky injection practices and drug use patterns among women who self-identified as participating in the sex trade with those who did not identify as participating in the sex trade. Logistic regression was used to identify factors independently associated with exchanging sex for money or drugs. HIV prevalence at the study visit (September 1999-2000) was 29% for sex trade workers and 29.2% for non-sex trade workers. While patterns of sexual risk were similar, the risky injection practice and drug use patterns between sex trade workers and non-sex trade workers were markedly different. Logistic regression analysis of cross-sectional data revealed that independent behaviours associated with the sex trade included: greater than once per day use of heroin (adjusted OR 2.7), smokeable crack cocaine (adjusted OR=3.3) and borrowing used syringes (adjusted OR=2.0). Creative, client-driven interventions are urgently needed for women who trade sex for money or for drugs.

The Cedar Project: historical trauma, sexual abuse and HIV risk among young Aboriginal people who use injection and non-injection drugs in two Canadian cities

Recent Indigenist scholarship has situated high rates of traumatic life experiences, including sexual abuse, among Indigenous peoples of North America within the larger context of their status as colonized peoples. Sexual abuse has been linked to many negative health outcomes including mental, sexual and drug-related vulnerabilities. There is a paucity of research in Canada addressing the relationship between antecedent sexual abuse and negative health outcomes among Aboriginal people including elevated risk of HIV infection. The primary objectives of this study were to determine factors associated with sexual abuse among participants of the Cedar Project, a cohort of young Aboriginal people between the ages of 14 and 30 years who use injection and non-injection drugs in two urban centres in British Columbia, Canada; and to locate findings through a lens of historical and intergenerational trauma. We utilized post-colonial perspectives in research design, problem formulation and the interpretation of results. Multivariate modeling was used to determine the extent to which a history of sexual abuse was predictive of negative health outcomes and vulnerability to HIV infection. Of the 543 eligible participants, 48% reported ever having experienced sexual abuse; 69% of sexually abused participants were female. The median age of first sexual abuse was 6 years for both female and male participants. After adjusting for sociodemographic variables and factors of historical trauma, sexually abused participants were more likely to have ever been on the streets for more than three nights, to have ever self-harmed, to have suicide ideation, to have attempted suicide, to have a diagnosis of mental illness, to have been in the emergency department within the previous 6 months, to have had over 20 lifetime sexual partners, to have ever been paid for sex and to have ever overdosed. The prevalence and consequences of sexual abuse among Cedar Project participants are of grave concern. Sexual trauma will continue to impact individuals, families and communities until unresolved historical trauma is meaningfully addressed in client-driven, culturally safe programming.

Itraconazole cyclodextrin solution for fluconazole-refractory oropharyngeal candidiasis in AIDS: correlation of clinical response with in vitro susceptibility.

Objective:To evaluate the efficacy of itraconazole cyclodextrin solution in fluconazole-refractory oropharyngeal candidiasis (OPC), and to correlate clinical outcome with in vitro susceptibility and serum azole levels. Design:A prospective, open-label, intervention study. Setting:A university hospital, which serves as the provincial HIV referral center. Patients and interventions:Thirty-six HIV-infected individuals referred for fluconazole-refractory OPC were evaluated prospectively between May 1993 and March 1995, including clinical assessment, serum azole levels, and susceptibility testing of Candida spp. isolates. Itraconazole solution was administered orally at a daily dose of 200 mg for 14 days, followed by suppressive therapy. Thirty-four patients were evaluable. Main outcome measure:Resolution of oral pseudomembranous lesions. Results:Initial isolates were Candida albicans (n = 33), C. glabrata (n = 1), C. krusei (n = 1), and mixed infection with C. albicans and C. krusei (n = 1). Fluconazole serum levels obtained at the time of failed therapy ranged from 4.7 to 40 mg/l (median, 12.9 mg/l). Itraconazole was generally well tolerated. Clinical responses were observed in 65% (22 out of 34) of evaluable cases. Among the responders, relapse had occurred within 2 months for four (36%) out of 11 cases who continued with follow-up. The median fluconazole minimal inhibitory concentration (MIC) was 64 mg/l for isolates from fluconazole-refractory cases, compared with a median of 0.5 mg/l for control isolates (P = 0.002). The median itraconazole MIC for isolates from fluconazole-refractory cases was 1.25 mg/l, compared with a median of 0.078 mg/l for controls (P = 0.011). Conclusion:A correlation between clinical response and in vitro susceptibility was clearly demonstrated for fluconazole, but not for itraconazole. Itraconazole cyclodextrin solution may be effective for fluconazole-refractory OPC and should be considered prior to salvage therapy with intravenous amphotericin B.

Increasing incidence of HIV infections among young gay and biseuxal 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 worlds 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.

Mycobacterial lymphadenitis associated with the initiation of combination antiretroviral therapy.

OBJECTIVE To characterize the impact of combination antiretroviral therapy on the clinical and laboratory features of mycobacterial lymphadenitis, we conducted a retrospective chart review of HIV-related mycobacterial lymphadenitis at St. Pauls hospital between 1989 and 1997. Among 52 evaluable patients, 12 presented within 12 weeks of initiating combination antiretroviral therapy (group 1, n = 12); the others developed lesions while receiving no antiretrovirals, monotherapy, or a stable combination regimen of >12 weeks duration (group 2, n = 40). RESULTS Group 1 patients had higher absolute CD4 lymphocyte counts (median, 150 versus 20 cells/mm3, respectively; p = .001) and hemoglobin levels (median, 113 versus 88 g/L, respectively; p = .002) at the time of mycobacterial diagnosis. Clinical comparison showed that group 1 patients were more likely to develop a draining sinus (50% versus 0%; p < .001), but less often to have weight loss (17% versus 74%; p < .0001) or disease which was disseminated (25% versus 70%; p = .04) or caused by Mycobacterium tuberculosis (0% versus 33%; p = .04). CONCLUSIONS Mycobacterial lymphadenitis developing within 12 weeks of initiating combination antiretroviral therapy is often localized Mycobacterium avium complex disease, associated with a relatively high CD4 count. The clinical course is often complicated by the development of a draining sinus. The close temporal association suggests that such treatment may unmask subclinical infection by enhancing the immune response to mycobacterial antigens.

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 Kaposis 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