Impact of Prior Tuberculosis Treatment With New/Companion Drugs on Clinical Outcomes in Patients Receiving Concomitant Bedaquiline and Delamanid for Multidrug- and Rifampicin-Resistant Tuberculosis.

BACKGROUND: There are scarce data on the clinical outcomes of persons retreated with new/companion anti-tuberculosis (TB) drugs for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We sought to evaluate the efficacy and safety of bedaquiline and delamanid containing regimens among patients with and without prior exposure to the new/companion drugs (bedaquiline, delamanid, linezolid, clofazimine, and fluoroquinolones). METHODS: We conducted a retrospective cohort study among patients with pulmonary MDR/RR-TB in Georgia who received bedaquiline and delamanid combination as a part of a salvage regimen from November 2017 to December 2020 in a programmatic setting. RESULTS: Among 106 persons with a median age of 39.5 years, 44 (41.5%) were previously treated with new/companion TB drugs. Patients with prior exposure to new/companion drugs had higher rates of baseline resistance compared to those without exposure to new/companion TB drugs (bedaquiline 15.2% vs 1.8%, linezolid 22.2% vs 16.7%). Sputum culture conversion rates among patients exposed and not exposed to new/companion drugs were 65.9% vs 98.0%, respectively (P < .001). Among patients with and without prior new/companion TB drug use, favorable outcome rates were 41.0% and 82.3%, respectively (P < .001). Treatment adherence in 32 (30.2%) patients was ≤80%. Five of 21 patients (23.8%) who had a baseline and repeat susceptibility test had acquired bedaquiline resistance. QTC/F prolongation (>500 ms) was rare (2.8%). CONCLUSIONS: Prior exposure to new/companion TB drugs was associated with poor clinical outcomes and acquired drug resistance. Tailoring the TB regimen to each patient's drug susceptibility test results and burden of disease and enhancing adherence support may improve outcomes.

Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/µL. We describe the demographics, HIV-specific characteristics and medical history of this cohort. METHODS: Data collected at baseline include demographics, HIV-specific laboratory values, prior medical diagnoses and concomitant medications. Baseline characteristics were compared by geographical region, gender and age. RESULTS: START enrolled 4685 HIV-positive participants from 215 sites in 35 countries. The median age is 36 years [interquartile range (IQR) 29-44 years], 27% are female, and 45% self-identify as white, 30% as black, 14% as Latino/Hispanic, 8% as Asian and 3% as other. The route of HIV acquisition is reported as men who have sex with men in 55% of participants, heterosexual sex in 38%, injecting drug use in 1% and other/unknown in 5%. Median time since HIV diagnosis is 1.0 year (IQR 0.4-3.0 years) and the median CD4 cell count and HIV RNA values at study entry are 651 cells/µL (IQR 584-765 cells/µL) and 12,754 HIV RNA copies/mL (IQR 3014-43,607 copies/mL), respectively. CONCLUSIONS: START has enrolled a diverse group of ART-naïve individuals with high CD4 cell counts who are comparable to the HIV-positive population from the regions in which they were enrolled. The information collected with this robust study design will provide a database with which to evaluate the risks and benefits of early ART use for many important outcomes.

Antiviral efficacy of entecavir in nucleos(t)ide-naïve patients of Black/African descent with chronic hepatitis B.

This single-arm, open-label, descriptive study assessed the efficacy and safety of entecavir (ETV) in nucleos(t)ide-naïve Black/African American patients with chronic hepatitis B (CHB), a patient population underrepresented in ETV registration trials. Forty patients with HBeAg(+) or HBeAg(-) compensated CHB of self-described Black/African American race received ETV 0.5 mg daily for 52 weeks; 37 patients completed 52 weeks of treatment. At Week 48, 29/40 (72.5%, noncompleter = failure) patients achieved the primary endpoint of HBV DNA <50 IU/mL. Rates for HBeAg loss (11/22; 50%) and HBeAg seroconversion (9/22; 41%) were high, possibly due to the high HBV genotype A prevalence (70%). No patient experienced virological breakthrough. Samples for resistance testing were available in 6/8 patients with HBV DNA >50 IU/mL at Week 48 or last on-treatment visit. No ETV resistance was detected. The safety profile of ETV was consistent with that observed in ETV registration trials. This study shows that in Black/African American patients with CHB, ETV was well tolerated and demonstrated comparable antiviral efficacy to that observed in White and Asian patients in ETV Phase III studies.

Factors associated with receiving CF care and use of telehealth in 2020 among persons with Cystic Fibrosis in the United States.

BACKGROUND: The COVID-19 pandemic resulted in the use of telehealth to deliver the cystic fibrosis (CF) care model, which recommends routine follow-up for monitoring of nutritional status, bacterial culture surveillance, pulmonary function testing, and screening for CF-related complications such as diabetes or osteoporosis. METHODS: The objective of this study was to use Cystic Fibrosis Foundation Patient Registry (CFFPR) data to quantify the extent to which persons with CF received the recommended components of the care model in 2019 versus 2020. A risk factor analysis was implemented to identify patient characteristics associated with attaining the recommended CF care and use of any telehealth using multivariable logistic regression. RESULTS: A total of 28,132 CFFPR participants were included in the study. The proportion of individuals meeting the recommendations for CF care was lower in 2020 for every indicator, and lower in adults compared to children. In adults, demographic, socioeconomic and CF-related disease covariates were significantly associated with both achieving an aggregate level of care and use of telehealth. In the pediatric population, minority race/ethnicity and markers of lower socioeconomic status were associated with a lower odds of telehealth use. In all analyses, having received the recommended level of care in 2019 was associated with a higher odds of both reported telehealth use and achieving the recommended elements of the CF care model in 2020. CONCLUSION: Fewer participants met recommendations for care in 2020 despite widespread use of telehealth, and use of telehealth did not equate to adherence to all aspects of CF care.

Inhaled mRNA therapy for treatment of cystic fibrosis: Interim results of a randomized, double-blind, placebo-controlled phase 1/2 clinical study.

BACKGROUND: MRT5005, a codon-optimized CFTR mRNA, delivered by aerosol in lipid nanoparticles, was designed as a genotype-agnostic treatment for CF lung disease. METHODS: This was a randomized, double-blind, placebo-controlled Phase 1/2 study performed in the US. Adults with 2 severe class I and/or II CFTR mutations and baseline ppFEV1 values between 50 and 90% were randomized 3:1 (MRT5005: placebo). Six dose levels of MRT5005 (4, 8, 12, 16, 20, and 24 mg) or placebo (0.9% Sodium Chloride) were administered by nebulization. The single ascending dose cohort was treated over a range from 8 to 24 mg; the multiple ascending dose cohort received five weekly doses (range 8-20 mg); and the daily dosing cohort received five daily doses (4 mg). RESULTS: A total of 42 subjects were assigned to MRT5005 [31] or placebo [11]. A total of 14 febrile reactions were observed in 10 MRT5005-treated participants, which were mild [3] or moderate [11] in severity; two subjects discontinued related to these events. Additionally, two MRT5005-treated patients experienced hypersensitivity reactions, which were managed conservatively. The most common treatment emergent adverse events were cough and headache. No consistent effects on FEV1 were noted. CONCLUSIONS: MRT5005 was generally safe and well tolerated through 28 days of follow-up after the last dose, though febrile and hypersensitivity reactions were noted. The majority of these reactions resolved within 1-2 days with supportive care allowing continued treatment with MRT5005 and careful monitoring. In this small first-in-human study, FEV1 remained stable after treatment, but no beneficial effects on FEV1 were observed.

Urethral duplication as cause of incontinence in a 5-years-old female: Surgical approach.

INTRODUCTION: Duplication of the urethra is a rare congenital anomaly in females which, if left unidentified, might cause refractory urinary incontinence. This video demonstrates its identification and treatment. PATIENT & METHODS: A 5-year-old female was referred for primary refractory diurnal incontinence without any dry moment since birth. Initial clinical examination showed permanent urine leakage from an opening cranial to the clitoris. Ultrasound did not show any bladder or kidney abnormalities. A diagnostic cystoscopy under anesthesia revealed an accessory meatus located cranially to the orthotopic meatus and to the clitoris. RESULTS: Lying in dorsal decubitus under general anesthesia, catheters were inserted in respectively the orthotopic and accessory meatus. The accessory meatus and urethra were dissected away into the bladder dome from a circumferential skin incision. Defects were closed and bladder drainage per urethram was left in situ for 10 days. P ostoperative recovery was uncomplicated. Complete resolution of the incontinence was immediately achieved at catheter removal. Daytime and night-time continence are observed with 3 years follow-up. CONCLUSION: Urethral duplication is a rare finding in females but should be excluded during the workup of primary incontinence. In girls with isolated urethral duplication, resection of the accessory urethra is the best surgical option.

Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings.

Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely.

Linezolid use for drug-resistant tuberculosis in Georgia: a retrospective cohort study.

SETTING: Data on the long-term use of linezolid (LZD) in the treatment of drug-resistant pulmonary tuberculosis (DR-PTB) are limited.OBJECTIVE: To assess safety, tolerability and efficacy of LZD-containing regimens for the treatment of DR-PTB in the country of Georgia.DESIGN: A retrospective study was conducted among DR-PTB patients receiving LZD 600 mg/day as part of newly implemented regimens (bedaquiline or delamanid, repurposed and second-line drugs) from July 2014 to October 2015 in programmatic conditions and following WHO recommendations.RESULTS: One hundred mostly male (82%) patients with a median age of 33 years received LZD. Most patients (77%) had previously been treated for TB; 57% had extensively drug-resistant TB. The median duration of LZD use was 503 days (interquartile range 355-616). LZD-associated adverse events occurred in 12 patients, leading to discontinuation in 4 (2 each due to peripheral neuropathy and cytopenias), and dose reduction to 300 mg/day in 6 cases (4 due to peripheral neuropathy and 2 for cytopenias). Almost all patients (95%) achieved culture conversion and 79% had a successful treatment outcomes.CONCLUSION: Treatment regimens including lengthy LZD use showed fairly good safety and tolerability and were associated with high rates of culture conversion and favorable outcomes.

Evaluation of a comprehensive diabetic foot ulcer care quality model.

AIMS: Diabetes-related amputations are typically preceded by a diabetic foot ulcer (DFU) but models to assess the quality of care are lacking. We investigated a model to measure inpatient and outpatient quality. METHODS: Cohort study among adults hospitalized with a DFU to a safety-net hospital during 2016. We measured adherence to DFU-related quality metrics based on guidelines during and 12 months following hospitalization. Inpatient metrics included ankle-brachial index measurement during or 6 months prior to hospitalization, receiving diabetes education and a wound offloading device prior to discharge. Outpatient metrics included wound care ≤30 days of discharge, in addition to hemoglobin A1c (HbA1c) ≤8%, tobacco cessation, and retention in care (≥2 clinic visits ≥90 days apart) 12 months following discharge. RESULTS: 323 patients were included. Regarding inpatient metrics, 8% had an ankle brachial index measurement, 37% received diabetes education, and 20% received offloading prior to discharge. Regarding outpatient metrics, 33% received wound care ≤30 days of discharge. Twelve months following discharge, 34% achieved a HbA1c ≤8%, 13% quit tobacco, and 52% were retained in care. Twelve-month amputation-free survival was 71%. CONCLUSIONS: Our model demonstrated large gaps in DFU guideline-adherent care. Implementing measures to close these gaps could prevent amputations.

Photoperiod manipulation of insect diapause: a method of pest control?

Extension of day length by artificial light in selected field plots in the fall prevented 76 percent of European corn borer [Ostrinia nubilalis (Hübner)] larvae and 70 percent of codling moth [Laspeyresia pomonella (L.)] larvae from entering diapause. Nondiapausing insects cannot survive rigorous winter conditions.

The Cedar Project: exploring determinants of psychological distress among young Indigenous people who use drugs in three Canadian cities.

BACKGROUND: Mental health and wellbeing, including addressing impacts of historical trauma and substance use among young people, has been identified as a key priority by Indigenous communities and leaders across Canada and globally. Yet, research to understand mental health among young Indigenous people who have used drugs is limited. AIMS: To examine longitudinal risk and strengths-based factors associated with psychological distress among young Indigenous people who use drugs. METHOD: The Cedar Project is an ongoing cohort study involving young Indigenous people who use drugs in Vancouver, Prince George, and Chase, British Columbia, Canada. This study included participants who completed the Symptom Checklist-90-Revised, returned for follow-up between 2010 and 2012, and completed the Childhood Trauma Questionnaire. Adjusted linear mixed-effects models estimated effects of study variables on changes in area T-scores of psychological distress. RESULTS: Of 202 eligible participants, 53% were women and the mean age was 28 years. Among men, childhood maltreatment (emotional abuse, physical abuse, sexual abuse, physical neglect), any drug use, blackouts from drinking, and sex work were associated with increased distress. Among women, childhood maltreatment (emotional abuse, physical abuse, physical neglect), blackouts from drinking, and sexual assault were associated with increased distress, while having attempted to quit using drugs was associated with reduced distress. Marginal associations were observed between speaking their traditional language and living by traditional culture with lower distress among men. CONCLUSION: Culturally safe mental wellness interventions are urgently needed to address childhood trauma and harmful coping strategies that exacerbate distress among young Indigenous people who use drugs.

Effectiveness of highly active antiretroviral therapy using non-brand name drugs in Brazil.

In Brazil, HIV-infected individuals receive drugs (including non-brand name drugs which comprise locally produced generics and drugs that have not been tested in bioequivalence trials) free of charge from the government. The objective of the present study was to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in Rio de Janeiro, Brazil, where non-brand drugs are widely used. For this purpose, we estimated the proportion of subjects with virologic failure (plasma HIV viral load greater than 400 copies/mL at 6 months after initiation of treatment). This was a retrospective cohort study of drug-naive HIV-infected subjects who initiated HAART. Subjects were included in the analysis if they were 18 years of age or older, were treatment naive, started HAART with a minimum of 3 drugs, and had available information on blood plasma HIV-1 viral load after 6 months on therapy. All subjects used antiretrovirals in dosing regimens recommended by the Brazilian National Advisory Committee for Antiretroviral Therapy. Chart reviews were conducted in three settings: at two public health outpatient units, at one clinical trial unit and at one private office. No comparisons of the effectiveness of non-brand name with the effectiveness of brand name drugs were made. We present results for 485 patients; of these, 354 (73%), 55 (11%), and 76 (16%) were seen at the public health outpatient units, private office, and clinical trial unit, respectively. Virologic failure was observed in 119 (25%) of the subjects. This study demonstrates the effectiveness of HAART in a setting where non-brand name drugs are widely used.

Effects of hyperthermia on primary and metastatic tumor growth and host immune response in rats.

A hot water bath was used to heat locally a metastasizing carcinoma in Wistar/Furth rats. Applying heat such that intratumor temperature is maintained at a mean value of 42.3 degrees for two 90-min sessions results in a decreased growth rate of the primary tumor as well as distant metastases. Heating the primary tumor for only one 90-min session or heating the leg contralateral to the tumor-bearing limb has no effect on the growth rate of either the primary tumor or metastases. Heat therapy has no detrimental effect on the spleen cell-mediated tumor immune response of rats as tested by an in vitro lymphocytotoxicity assay 1 day later. However, heating isolated spleen cells to similar temperatures in vitro reduces their capacity for in vitro tumor cell killing.

Protease inhibitors as initial therapy for individuals with an intermediate risk of HIV disease progression: is more necessarily better?

OBJECTIVE: To compare three possible therapeutic strategies for the treatment of patients with an intermediate risk of HIV disease progression. DESIGN: Mathematical modeling based on assumptions derived from published data. METHODS: A parametric survival model was fitted to empirical data to describe the survival trajectory of untreated individuals. It was assumed that successful treatment decreases the risk of disease progression curing the first year after its introduction by a constant that is dependent on the magnitude of the initial drop in HIV viral load. Thereafter, individual members of the treatment cohort follow different pathways, depending on the duration of the initial response or, in case of virologic failure, the response to a new drug regimen. RESULTS: Sub-groups of patients starting therapy with two nucleoside reverse transcriptase inhibitors (NRTI) or two NRTI and a protease inhibitor had the highest instantaneous risk of disease progression at the end of the 5-year follow-up period. Patients who started therapy with two NRTI and a non-NRTI had the lowest likelihood of progression to AIDS or death at 5 years of follow-up. This is because, in the case of the subgroup whose initial treatment included a protease inhibitor, failure rates due to non-adherence to therapy are high and response to salvage therapy is limited by past protease inhibitor experience. CONCLUSIONS: Despite the superior virologic potency of the protease inhibitor-containing regimens, in this analysis other strategies performed equally well or even better. In the absence of solid empirical data and until the advent of antiretroviral regimens that are shown to be safe, simple to take, and maximally suppress viral load, caution may be required in selecting the long-term therapy for patients with less advanced HIV disease.

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.

Chemoprophylaxis for tuberculosis and survival of HIV-infected patients in Brazil.

OBJECTIVE: To study the impact of chemoprophylaxis for tuberculosis on the survival of HIV-infected patients with a positive tuberculin skin test. DESIGN: Prospective observational cohort study. SETTING: Outpatient clinic of a university hospital, in Rio de Janeiro, Brazil. PATIENTS: Two-hundred and ninety-seven patients with a positive tuberculin skin test (reaction > or = 5mm) who were admitted to the cohort between January 1991 and December 1994. Follow-up ended on September 30, 1998. INTERVENTION: The use of chemoprophylaxis for tuberculosis. MAIN OUTCOME MEASURES: Death was the primary outcome variable. The occurrence of tuberculosis was studied as a secondary outcome. Cox regression models were used in these analyses. RESULTS: The median follow-up time was 43.6 months. Chemoprophylaxis was used by 128 (43%) of the patients. The use of chemoprophylaxis was associated with a reduction in risk for tuberculosis (hazard ratio, 0.38; 95% confidence interval, 0.14-1.04; P = 0.05). In a regression model adjusted for baseline CD4 cell count, chemoprophylaxis was associated with longer survival (hazard ratio, 0.24; 95% confidence interval, 0.09-0.65; P = 0.002). CONCLUSIONS: Anti-tuberculosis chemoprophylaxis was associated with a substantially prolonged survival among purified protein derivative-positive HIV-infected patients in Brazil. These data have important implications for the clinical care of patients with HIV infection in areas of the world with a high prevalence of Mycobacterium tuberculosis infection.

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.

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.

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.

Needle exchange is not enough: lessons from the Vancouver injecting drug use study.

OBJECTIVE: To describe prevalence and incidence of HIV-1, hepatitis C virus (HCV) and risk behaviours in a prospective cohort of injecting drugs users (IDU). SETTING: Vancouver, which introduced a needle exchange programme (NEP) in 1988, and currently exchanges over 2 million needles per year. DESIGN: IDU who had injected illicit drugs within the previous month were recruited through street outreach. At baseline and semi-annually, subjects underwent serology for HIV-1 and HCV, and questionnaires on demographics, behaviours and NEP attendance were completed. Logistic regression analysis was used to identify determinants of HIV prevalence. RESULTS: Of 1006 IDU, 65% were men, and either white (65%) or Native (27%). Prevalence rates of HIV-1 and HCV were 23 and 88%, respectively. The majority (92%) had attended Vancouver's NEP, which was the most important syringe source for 78%. Identical proportions of known HIV-positive and HIV-negative IDU reported lending used syringes (40%). Of HIV-negative IDU, 39% borrowed used needles within the previous 6 months. Relative to HIV-negative IDU, HIV-positive IDU were more likely to frequently inject cocaine (72 versus 62%; P < 0.001). Independent predictors of HIV-positive serostatus were low education, unstable housing, commercial sex, borrowing needles, being an established IDU, injecting with others, and frequent NEP attendance. Based on 24 seroconversions among 257 follow-up visits, estimated HIV incidence was 18.6 per 100 person-years (95% confidence interval, 11.1-26.0). CONCLUSIONS: Despite having the largest NEP in North America, Vancouver has been experiencing an ongoing HIV epidemic. Whereas NEP are crucial for sterile syringe provision, they should be considered one component of a comprehensive programme including counselling, support and education.