Biomedical subjects
Publications and source records attributed to Susan Brogly.
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OBJECTIVE: To examine the relationship between the use of highly active antiretroviral treatment (HAART) and the occurrence of opportunistic illnesses (OIs) among children perinatally infected with human immunodeficiency virus. DESIGN: Prospective cohort study. SETTING: Pediatric AIDS Clinical Trials Group 219C cohort. PARTICIPANTS: From September 15, 2000, to August 31, 2003, 1927 children perinatally infected with human immunodeficiency virus and receiving HAART were followed up. Main Exposures Age at initiating HAART, duration of HAART use, CD4+ T-lymphocyte percentage, and human immunodeficiency virus 1 viral load. MAIN OUTCOME MEASURES: Incidence rates for Centers for Disease Control and Prevention OI category B and OI category C events were calculated. The association between main exposures and OI occurrence was estimated using proportional hazards regression. RESULTS: Of 1927 subjects, 226 (12.7%) developed OIs during follow-up. Incidence rates were 4.99 per 100 person-years (95% confidence interval, 4.30-5.76) for first OI category B events and 1.47 per 100 person-years (95% confidence interval, 1.12-1.91) for first OI category C events. Duration of HAART use was not related to OI risk. Older age (age >10 years) at HAART initiation was associated with increased risk of a first OI (hazard ratio, 2.48; 95% confidence interval, 1.23-5.00) compared with initiating HAART in children younger than 2 years. This increased risk diminished after adjusting for CD4+ T-lymphocyte percentage and Centers for Disease Control and Prevention disease category at HAART initiation. More children with OIs than without OIs had a CD4+ T-lymphocyte percentage of less than 15% at HAART initiation (49.6% of children with OIs vs 23.7% of children without OIs), at enrollment (41.2% of children with OIs vs 7.7% of children without OIs), and at the end of follow-up (41.2% of children with OIs vs 8.3% of children without OIs). CONCLUSIONS: Opportunistic illnesses are occurring in the pediatric human immunodeficiency virus population in the HAART era, mainly in children with persistently low CD4+ T-lymphocyte percentages. Lack of a sustained response to HAART rather than age at or duration of HAART use is predictive of OI risk.
CONTEXT: Antiretroviral therapy (ART) for pediatric human immunodeficiency virus (HIV) infection has evolved from simple nucleoside reverse transcriptase inhibitor (NRTI) regimens to complex combination therapies based largely on evidence from clinical trials. However, the integration of novel ART into the clinical care of pediatric HIV infection has not been examined. OBJECTIVES: To describe changes in the treatment of pediatric HIV infection in the United States from 1987-2003, to assess concordance of initial regimens with US pediatric guidelines, and to identify predictors of the first regimen switch. DESIGN, SETTING, AND PARTICIPANTS: The study population included 766 perinatally HIV-infected children in the Pediatric AIDS Clinical Trials Group 219C cohort born before January 1, 2004, who had not participated in an ART clinical trial at 219C enrollment or during follow-up. MAIN OUTCOME MEASURES: Proportion of children receiving specific ART regimens, proportion of children initiating ART according to pediatric guidelines, and time to first regimen switch (risk of switching). RESULTS: Single and dual NRTI regimens were used most frequently through 1997. In 1998, 2 years after protease inhibitors were approved for adult HIV infection and at the time pediatric guidelines were issued, regimens of highly active antiretroviral therapy including a protease inhibitor became most frequently used. From 1998-2003, 22% of children initiated ART with a regimen not recommended by pediatric guidelines. In multivariate regression, the risk of switching decreased with age at ART initiation (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.99) and increased with year of initiation (HR, 1.28; 95% CI, 1.23-1.33). The risk of switching was higher in children who started with 1 NRTI (HR, 8.05; 95% CI, 5.80-11.18), 2 NRTIs (HR, 4.08; 95% CI, 3.08-5.40), or an unconventional regimen (HR, 6.23; 95% CI, 3.36-11.54) vs children who started with a protease inhibitor-containing regimen; and in children who initiated ART at CD4 T lymphocyte percentages less than 15 vs 15 or greater (HR, 2.90; 95% CI, 1.03-8.13). CONCLUSIONS: There was a short lag between the identification of novel ART and its adoption in the pediatric community. A variety of regimens were used, including some unorthodox therapies. Important predictors of first regimen switch were identified.
OBJECTIVES: To determine the incidence of and factors associated with malignancy in perinatally human immunodeficiency virus (HIV)-infected children in the United States. METHODS: Included were 2969 children followed in the Pediatric AIDS Clinical Trials Group (PACTG) 219/219C cohort from 1993 through 2003. Cancer incidence by sex, race, age, histology and highly active antiretroviral therapy (HAART) era (pre-HAART, 1993-1997; HAART, 1998-2003) was estimated, and the standardized incidence ratio contrasting infected and uninfected children was determined. Poisson regression was used to further investigate the relation between HAART use (> or =3 drugs of > or =2 classes, 1 of which was a protease inhibitor), CD4% and cancer. RESULTS: There were 37 cancers (17 prevalent and 20 incident) diagnosed in 2969 children for a prevalence of 0.6% [95% confidence interval (CI), 0.3, 0.9] and an incidence of 1.56/1000 person-years (95% CI 0.95, 2.41). Compared with uninfected children, the standardized incidence ratio was 10.08 (95% CI 5.87, 16.14). Incidence did not significantly differ by sex, race, age or HAART era. Of the cases, 35% were immunocompetent (CD4 > or =25%), 25% were moderately immunosuppressed (15%< or = CD4 < or =24%) and 40% were severely immunosuppressed (CD4 <15%) at diagnosis. In multivariate regression, the cancer rate was 3.09 (95% CI 1.22, 7.85) times higher in children with < or =2 years of HAART use than in children with >2 years of HAART and 3.20 (95% CI 1.32, 7.76) times higher in children with CD4 <15% at cohort enrollment than in children with CD4 > or =15%. CONCLUSION: Cancer incidence in this U.S. pediatric cohort was lower than that of European cohorts but was markedly higher than that of HIV-uninfected children. Cancer incidence was highest in children who were severely immunosuppressed and in children who received HAART for < or =2 years.
The psychometric properties of the Injection Drug User Quality of Life Scale (IDUQOL) were assessed in 61 Montreal IDUs in 2001, 85% of whom were reinterviewed within four weeks. The reliability of the IDUQOL was acceptable (ICC = 0.71) and concordance between the IDUQOL and the Flanagan Quality of Life Scale was moderate (Pearson coefficient = 0.57). Quality of life was negatively associated with injection cocaine and emergency department use with both instruments; these results were more striking for the IDUQOL. The IDUQOL is a culturally relevant quality of life instrument with good psychometric properties. The IDUQOL may be useful in the development and evaluation of interventions for IDUs.
Access to clean needles and syringes through needle exchange programs (NEPs) has reduced both high-risk behaviors and the transmission of blood-borne infections among injection drug users (IDUs). However, policies regarding "needle-for-needle" exchange versus unrestricted needle distribution remain controversial. The objective of this study was to compare sources of needles, trends in needle distribution, and the practice of satellite needle distribution (SND) among IDUs in Vancouver and Montreal. SND was defined as receiving a new syringe from another individual through trading, purchasing, borrowing, or being given the syringe outright, or supplying a syringe to another individual through trading, selling, lending, or giving a syringe outright. This was practiced by 46% of IDUs in Vancouver and 50% of IDUs in Montreal. SND was associated with borrowing used injection equipment (adjusted OR [AOR], 2.62; 95% CI: 1.85-3.71), conducting bulk needle exchanges (AOR, 1.85; 95% CI: 1.34-2.54), being married or in a common-law relationship (AOR, 1.85; 95% CI: 1.34-2.54), and regular visits to the NEP (> weekly) (AOR, 1.54; 95% CI: 1.17-2.13). In Vancouver, SND was also associated with borrowing used needles (AOR, 2.07; 95% CI: 1.22-3.52). In these two cities, despite different distribution policies, almost half of the participants reported SND, and this was associated with high risk sharing. The practice of SND appears to be an important mechanism for needle acquisition, especially for those at highest risk for HIV and hepatitis C transmission.
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