Efficacy of systemic sirolimus in the treatment of generalized lymphatic anomaly and Gorham-Stout disease.

BACKGROUND: Generalized lymphatic anomaly (GLA) and Gorham-Stout disease (GSD) are rare complicated lymphatic malformations that occur in multiple body sites and are associated with significant morbidity and mortality. Treatment options have been limited, and conventional medical therapies have been generally ineffective. Emerging data suggest a role for sirolimus as a treatment option for complex lymphatic anomalies. PROCEDURE: Disease response was evaluated by radiologic imaging, quality of life (QOL), and clinical status assessments in children and young adults with GLA and GSD from a multicenter systematic retrospective review of patients treated with oral sirolimus and the prospective phase 2 clinical trial assessing the efficacy and safety of sirolimus in complicated vascular anomalies (NCT00975819). Sirolimus dosing regimens and toxicities were also assessed. RESULTS: Eighteen children and young adults with GLA (n = 13) or GSD (n = 5) received oral sirolimus. Fifteen patients (83%) had improvement in one or more aspects of their disease (QOL 78%, clinical status 72%, imaging 28%). No patients with bone involvement had progression of bone disease, and the majority had symptom or functional improvement on sirolimus. Improvement of pleural and pericardial effusion(s) occurred in 72% and 50% of affected patients; no effusions worsened on treatment. CONCLUSIONS: Sirolimus appears effective at stabilizing or reducing signs/symptoms of disease in patients with GLA and GSD. Functional impairment and/or QOL improved in the majority of individuals with GLA and GSD with sirolimus treatment.

A xenograft model for venous malformation.

Vascular malformations are defects caused by the abnormal growth of the vasculature. Among them, venous malformation (VM) is an anomaly characterized by slow-flow vascular lesions with abnormally shaped veins, typically in sponge-like configuration. VMs can expand over years causing disfigurement, obstruction of vital structures, thrombosis, bleeding, and pain. Treatments have been very limited and primarily based on supportive care, compression garments, sclerotherapy, and/or surgical resection. Sirolimus treatment has recently shown efficacy in some patients with complicated vascular anomalies, including VMs. Activating somatic TIE2 gene mutations have been identified in up to 60% of VMs and PIK3CA mutations have been found in another 25%. Here, we report a xenograft model of VM that reflects the patients' mutation heterogeneity. First, we established a protocol to isolate and expand in culture endothelial cells (VM-EC) from VM tissue or VM blood of nine patients. In these cells, we identified somatic mutations of TIE2, PIK3CA, or a combination of both. Both TIE2 and PIK3CA mutations induced constitutive AKT activation, while TIE2 mutations also showed high MAPK-ERK signaling. Finally, VM-EC implanted into immune-deficient mice generated lesions with ectatic blood-filled channels with scarce smooth muscle cell coverage, similar to patients' VM. This VM xenograft model could be instrumental to test the therapeutic efficacy of Sirolimus in the presence of the different TIE2 or PIK3CA mutations or to test for efficacy of additional compounds in targeting the specific mutated protein(s), thus enabling development of personalized treatment options for VM patients.

Angiopoietins as serum biomarkers for lymphatic anomalies.

Vascular anomalies can cause significant morbidity and mortality. Advances in diagnosis will be improved if noninvasive biomarkers can be identified, as obtaining a tissue biopsy can worsen the disease and precipitate complications. The goal of this study was to identify biomarkers for vascular anomaly patients to aid diagnosis and potentially give insights into pathogenesis. Blood was collected at baseline and then 6 and 12 months after treatment with the mTOR inhibitor sirolimus. Patients groups included generalized lymphatic anomaly (GLA), kaposiform lymphangiomatosis (KLA) and kaposiform hemangioendothelioma (KHE) with or without the Kasabach-Merritt phenomenon (KMP) coagulopathy. Serum was obtained from healthy controls selected to match the age and sex of the patients (21 days-28.5 years; 42% males; 58% females). Angiogenic and lymphangiogenic factors (VEGF-A, C, D, Ang-1 and Ang-2) were measured in serum using ELISA. In lymphatic anomaly patients, baseline levels of VEGF-A and VEGF-D were not different compared to controls. Angiopoietin-2 (Ang-2) levels were near controls levels in GLA patients but 10-fold greater in KLA patients and 14-fold greater in KHE patients when the KMP coagulopathy was present but not when it was absent. VEGF-C and angiopoietin-1 (Ang-1) levels were lower in KHE patients with KMP. Our analyses suggest that Ang-2 and Ang-1 can be used as biomarkers to help identify KLA and KHE patients with KMP coagulopathy with high sensitivity and specificity. After 12 months of sirolimus treatment, Ang-2 levels were lower in KLA and KHE with KMP patients compared to baseline levels and with most patients showing a clinical response. Hence, serum Ang-2 and Ang-1 levels may help in the diagnosis of patients with lymphatic anomalies and are concordant to sirolimus response.

Developmental pharmacokinetics of sirolimus: Implications for precision dosing in neonates and infants with complicated vascular anomalies.

BACKGROUND: Sirolimus has recently been shown to be efficacious and tolerable in pediatric patients with complicated vascular anomalies. Nevertheless, dosing information remains very limited especially for neonates and infants. The purpose of this study was to develop an age-appropriate sirolimus starting dosing regimen based on the developmental changes in drug elimination capacity using data collected in neonates and infants. PROCEDURE: A recently developed sirolimus maturation model [Emoto et al. CPT Pharmacometrics Syst Pharmacol, 2016] was used to simulate clearance estimates using realistic age and weight covariates for age cohorts aged 0-24 months. Next, predose concentrations at steady state were generated for each age cohort of neonates and infants. Dose requirements to attain predefined target trough concentration ranges (10-15 and 5-10 ng/ml) were simulated across the different age groups. Starting doses were chosen to maximize the likelihood of achieving sirolimus-targeted concentrations. RESULTS: The trajectory of simulated sirolimus clearances increased with age and was in agreement with the previous findings in the Phase 2 study. The proposed dosing regimens covered eight age cohorts and resulted in target attainment of more than 75-95% across selected regimens. CONCLUSIONS: This study identified age-appropriate sirolimus dosing regimens for neonates and infants. The algorithm in combination with therapeutic drug management will facilitate sirolimus precision dosing in young children with vascular anomalies. A prospective evaluation is being planned.

Response of Blue Rubber Bleb Nevus Syndrome to Sirolimus Treatment.

BACKGROUND: Blue rubber bleb nevus syndrome (BRBNS) is a rare multifocal venous malformation syndrome involving predominantly the skin and gastrointestinal tract. Traditional treatment modalities include corticosteroids, interferon-α, sclerotherapy, and aggressive surgical resection. Sirolimus has been used in several single case reports. PROCEDURE: We performed a single-institution retrospective review of four children with BRBNS, who received sirolimus as part of their treatment regimens. A diagnosis of BRBNS was based on clinical, radiologic, and pathologic criteria. RESULTS: Median age was 6.5 years (range: 2-16 years). Pathologic evaluations revealed a combined malformation with venous and lymphatic components. The novel finding of a lymphatic component was confirmed with PROX-1 immunostaining. Patients received oral sirolimus with target drug levels between 10 and 13 ng/ml. Responses to treatment were defined as stabilization/decrease in size of lesions; resolution of transfusion requirements; reduction in pain, and improvement in quality of life (QOL). Median time to response was 1.5 months (SD ± 0.96 month, range: 1-3 months). Median follow-up was 21 months (range: 18-26 months). Lesion size and characteristics improved in all patients. All patients reported decrease in pain and improvement in QOL. All three patients requiring transfusions became transfusion-independent. One patient had resolution of coagulopathy. Adverse effects of sirolimus consisted of mucositis in three patients and neutropenia in one patient. CONCLUSIONS: Sirolimus is safe and efficient for the treatment of BRBNS. Further prospective studies are needed to evaluate the long-term effectiveness of this drug. This is the first report that identifies a lymphatic component as part of BRBNS.

The effect of highly active antiretroviral therapy on human papillomavirus clearance and cervical cytology.

OBJECTIVE: To examine the association of highly active antiretroviral therapy (HAART) with human papillomavirus (HPV) clearance and progression or regression of cervical cytological abnormalities in women with human immunodeficiency virus (HIV). METHODS: Five hundred thirty-seven women with HIV participating in the HIV Epidemiology Research Study, an observational, multisite cohort study, were evaluated semiannually from 1996 to 2000. Cervical Pap tests were collected for cervical cytology. Testing for HPV was conducted by polymerase chain reaction. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals (CIs). Number needed to treat (NNT) at 2 years was calculated for HAART. RESULTS: Among women with cervical squamous intraepithelial lesions, HAART was associated with an increased likelihood of HPV clearance (hazard ratio 4.5, 95% CI 1.2-16.3, NNT 22.4). Use of HAART was not associated with an increased likelihood of HPV clearance among women with normal cervical cytology (hazard ratio 1.7, 95% CI 0.9-3.1, NNT 6.5) or atypical squamous cells of undetermined significance cytology (hazard ratio 1.0, 95% CI 0.4-2.5, NNT 174.0). Use of HAART was not significantly associated with an increased likelihood of cervical cytologic regression (hazard ratio 1.3, 95% CI 1.0-1.7, NNT 10.9) or cervical cytologic progression (hazard ratio 0.7, 95% CI 0.6-1.0, NNT 12.8). CONCLUSION: Among women with preexisting abnormal cervical cytology, HAART was associated with enhanced HPV clearance but not with Pap test regression. Close monitoring of women with HIV for cervical cytologic abnormalities, regardless of HAART treatment status, is warranted. LEVEL OF EVIDENCE: II.

Longitudinal association of alcohol use with HIV disease progression and psychological health of women with HIV.

We evaluated the association of alcohol consumption and depression, and their effects on HIV disease progression among women with HIV. The study included 871 women with HIV who were recruited from 1993-1995 in four US cities. The participants had physical examination, medical record extraction, and venipuncture, CD4+T-cell counts determination, measurement of depression symptoms (using the self-report Center for Epidemiological Studies-Depression Scale), and alcohol use assessment at enrollment, and semiannually until March 2000. Multilevel random coefficient ordinal models as well as multilevel models with joint responses were used in the analysis. There was no significant association between level of alcohol use and CD4+ T-cell counts. When participants were stratified by antiretroviral therapy (ART) use, the association between alcohol and CD4+ T-cell did not reach statistical significance. The association between alcohol consumption and depression was significant (p<0.001). Depression had a significant negative effect on CD4+ T-cell counts over time regardless of ART use. Our findings suggest that alcohol consumption has a direct association with depression. Moreover, depression is associated with HIV disease progression. Our findings have implications for the provision of alcohol use interventions and psychological resources to improve the health of women with HIV.

Psychological resources protect health: 5-year survival and immune function among HIV-infected women from four US cities.

OBJECTIVE: Guided by Cognitive Adaptation Theory, the aim was to determine whether psychological resources (positive affect, positive expectancy regarding health outcomes, finding meaning in challenging circumstances) protect against HIV-related mortality and decline in CD4 lymphocyte counts among women with HIV. DESIGN: The HIV Epidemiologic Research Study, a longitudinal prospective cohort study, with semi-annual interview, physical examination and laboratory assays. METHODS: A total of 773 HIV-seropositive women aged 16 to 55 years were recruited from four academic medical centers in Baltimore, Maryland; Bronx, New York; Providence, Rhode Island; and Detroit, Michigan. Semi-annually for up to 5 years, the women were interviewed, underwent physical examination, medical record abstraction, and venipuncture. Primary outcomes for these analyses included HIV-related mortality and CD4 cell count slope decline over 5 years. RESULTS: Psychological resources were inversely associated with HIV-related mortality and time to death, beyond the effects of potential confounding variables such as clinical status (e.g., HIV viral load, symptoms, antiretroviral therapy), sociodemographic characteristics (e.g. age, race), and depression at study entry (P < 0.05). Psychological resources also were inversely associated with CD4+ cell count decline (P < 0.01), serving as a possible mechanism linking resources to mortality. CONCLUSIONS: Psychological resources may protect against HIV-related mortality and immune system decline. Findings have implications for understanding individual variability in HIV disease progression. Moreover, because psychological resources are potentially amenable to change, results can be applied to clinical interventions aimed at improving the health of women with HIV.

Effect of HIV infection on atypical squamous cells of undetermined significance.

BACKGROUND: Detection of atypical squamous cells of undetermined significance (ASCUS) is a cervical cytologic finding that is suggestive but not definitive of squamous intraepithelial lesions (SILs). METHODS: We examined the risk, characteristics, and progression of ASCUS in women with and without human immunodeficiency virus (HIV) infection. Cervical Papanicolou (Pap) test and colposcopy data were obtained at the first 10 semiannual visits for the HIV Epidemiology Research study of 774 HIV-infected and 480 demographically similar, HIV-uninfected women in the United States. Multiple logistic regression models and Cox proportional hazards models were utilized. RESULTS: ASCUS was more common among HIV-infected women (odds ratio [OR], 1.6 [95% confidence interval {CI}, 1.3-2.0] to 2.6 [95% CI, 1.9-3.6]) after adjustment for human papillomavirus (HPV) infection and other risk factors (e.g., race, condyloma, and prior Pap test result). Among women with normal Pap test results at enrollment, the cumulative incidence of ASCUS was 78% among HIV-infected women and 38% among HIV-uninfected women. HIV-infected and HIV-uninfected women with ASCUS did not differ by prevalence of indices of inflammation (inflammation on Pap test and leukocytes on cervical gram stain). HPV infection, including high risk types, was more common among HIV-infected women with ASCUS. Among women with ASCUS, 60% of HIV-infected and 25% of HIV-uninfected women developed SILs (P < .01). Compared with HIV-infected women with higher CD4+ lymphocyte counts, HIV-infected women with CD4+ lymphocyte counts < 200 cells/microL were more likely to present subsequently with a SIL detected by Pap test (OR, 1.7; 95% CI, 0.8-3.6). CONCLUSIONS: Higher risk of SIL following the appearance of ASCUS among HIV-infected women, especially women with low CD4+ lymphocyte counts, supports the need for follow up with colposcopy and histologic examination, as indicated, to allow early detection and treatment of SIL.

Bacterial pneumonia, HIV therapy, and disease progression among HIV-infected women in the HIV epidemiologic research (HER) study.

BACKGROUND: To determine the rate and predictors of community-acquired bacterial pneumonia and its effect on human immunodeficiency virus (HIV) disease progression in HIV-infected women, we performed a multiple-site, prospective study of HIV-infected women in 4 cities in the United States. METHODS: During the period of 1993-2000, we observed 885 HIV-infected and 425 HIV-uninfected women with a history of injection drug use or high-risk sexual behavior. Participants underwent semiannual interviews, and CD4+ lymphocyte count and viral load were assessed in HIV-infected subjects. Data regarding episodes of bacterial pneumonia were ascertained from medical record reviews. RESULTS: The rate of bacterial pneumonia among 885 HIV-infected women was 8.5 cases per 100 person-years, compared with 0.7 cases per 100 person-years in 425 HIV-uninfected women (P < .001). In analyses limited to follow-up after 1 January 1996, highly active antiretroviral therapy (HAART) and trimethoprim-sulfamethoxazole (TMP-SMX) use were associated with a decreased risk of bacterial pneumonia. Among women who had used TMP-SMX for 12 months, each month of HAART decreased bacterial pneumonia risk by 8% (adjusted hazard ratio [HR(adj)], 0.92; 95% confidence interval [CI], 0.89-0.95). Increments of 50 CD4+ cells/mm3 decreased the risk (HR(adj), 0.88; 95% CI, 0.84-0.93), and smoking doubled the risk (HR(adj), 2.12; 95% CI, 1.26-3.55). Bacterial pneumonia increased mortality risk (HR(adj), 5.02; 95% CI, 2.12-11.87), with adjustment for CD4+ lymphocyte count and duration of HAART and TMP-SMX use. CONCLUSIONS: High rates of bacterial pneumonia persist among HIV-infected women. Although HAART and TMP-SMX treatment decreased the risk, bacterial pneumonia was associated with an accelerated progression to death. Interventions that improve HAART utilization and promote smoking cessation among HIV-infected women are warranted.

Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies.

BACKGROUND AND OBJECTIVES: Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days. METHODS: Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m(2) per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths. RESULTS: Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred. CONCLUSIONS: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.

Interpersonal predictors of depression trajectories in women with HIV.

This article tests an interpersonal model of depression symptom trajectories tailored to the experiences of women with HIV. Specifically, the authors examined how bereavement, maternal role difficulty, HIV-related social isolation, and partner conflict predicted change in depressive symptoms over 5 years in 761 women with HIV, controlling for sociodemographic and clinical health factors. Of these interpersonal characteristics, partner conflict emerged as a robust predictor of change in depressive symptoms in growth curve and cross-lag models. Results highlight the need for interventions focusing on interpersonal issues, particularly intimate relationships, in women with HIV.

A prospective study of adherence and viral load in a large multi-center cohort of HIV-infected women.

OBJECTIVES: To examine the relationship between antiretroviral adherence and viral load, and to determine the predictors of adherence over time in HIV-infected women. DESIGN: Prospective observational study. METHODS: One-hundred sixty-one HIV-infected women who were taking antiretroviral therapy for a median of 3.0 years were recruited from the HIV Epidemiology Research Study, a multicenter cohort study of HIV infection in women. Antiretroviral adherence (percent of doses taken as prescribed) was measured over a 6-month period using MEMS caps. At baseline and follow-up, CD4 lymphocyte count and viral load were measured, and a standardized interview was administered to elicit medication history and drug use behaviors. To examine changes in adherence over time, the mean adherence to all antiretroviral agents was calculated for each monitored month. RESULTS: Adherence varied significantly over time (P < 0.001), ranging from a mean of 64% in month 1 to 45% in month 6. Nearly one-fourth of the participants had a 10% or greater decrease in adherence between consecutive months. Virologic failure occurred in 17% of women with adherence of > or = 88%, 28% of those with 45-87% adherence, 43% of those with 13-44% adherence, and 71% of those with < or = 12% adherence. In multivariate analysis, factors predicting lower adherence included active drug use, alcohol use, more frequent antiretroviral dosing, shorter duration of antiretroviral use, younger age, and lower initial CD4 lymphocyte count. CONCLUSIONS: Antiretroviral adherence is not stable over time. Interventions aimed at monitoring and improving long-term adherence in women are urgently needed.

Prevalence and cumulative incidence of and risk factors for anemia in a multicenter cohort study of human immunodeficiency virus-infected and -uninfected women.

We conducted a longitudinal study of 797 human immunodeficiency virus (HIV)-positive women (7732 visits) and 389 HIV-negative women (3651 visits) to characterize anemia. At enrollment, the prevalence of anemia was 28.1% among HIV-positive women and 15.1% among HIV-negative women (P<.0001), and during follow-up the cumulative incidence of anemia was 74% and 48%, respectively (P<.0001). Risk factors for anemia were African American race (odds ratio [OR], 2.15; 95% confidence interval [CI], 1.73-2.69), age (per 5-year increase; OR, 1.12; 95% CI, 1.03-1.21), body mass index (OR, 0.96; 95% CI, 0.94-0.97), history of pneumonia (OR, 1.41; 95% CI, 1.20-1.65), oral candidiasis (OR, 1.42; 95% CI, 1.22-1.66), CD4+ lymphocyte count <200 cells/microL (OR, 1.68; 95% CI, 1.46-1.94), history of fever (OR, 1.42; 95% CI, 1.13-1.80), and zidovudine use (OR, 1.14; 95% CI, 1.01-1.30). Anemia was common and associated with an increased risk of death (hazards ratio, 1.64; 95% CI, 1.21-2.23) among HIV-positive women.

Prevalence, incidence, and persistence or recurrence of trichomoniasis among human immunodeficiency virus (HIV)-positive women and among HIV-negative women at high risk for HIV infection.

Trichomoniasis has been implicated in the acquisition and transmission of human immunodeficiency virus (HIV) infection. The prevalence, incidence, and persistence or recurrence of trichomoniasis were assessed among HIV-positive women and among HIV-negative women at high risk for HIV infection. A total of 871 HIV-seropositive women and 439 HIV-seronegative women enrolled in the HIV Epidemiology Study (HERS) were seen biannually. The prevalence of trichomoniasis was 9.4%-29.5% among HIV-seropositive women and 8.2%-23.4% among HIV-seronegative women. Prevalence decreased over time, did not vary according to HIV status or CD4 cell count, and was higher among women who reported crack use (P=.02) or cigarette use (P=.02), women who had bacterial vaginosis (P=.02), and those who were black (compared with white women, P<.001). There were no differences, according to HIV status or CD4 cell count, in the adjusted incidence, unadjusted incidence, or persistence or recurrence of trichomoniasis. HIV infection does not make a woman more likely to have prevalent, incident, or persistent or recurrent trichomoniasis.

Overweight and human immunodeficiency virus (HIV) progression in women: associations HIV disease progression and changes in body mass index in women in the HIV epidemiology research study cohort.

An association of increased weight with a slower progression of human immunodeficiency virus (HIV) disease has been reported in studies that have not included large numbers of women. We evaluated the association of HIV disease progression with body mass index (BMI) in 871 women and present cross-sectional, survival, and longitudinal analyses. A higher baseline BMI was associated with a lower rate of occurrence of the first CD4 cell count <200 cells/mm(3). In analyses that incorporated time-varying BMI, underweight and normal women had an increased risk of clinical acquired immune deficiency syndrome, and underweight women had increased risk of HIV-related death, compared with obese women. The association between change in BMI and CD4 cell count was estimated; increases in BMI were associated with slight increases in CD4 cell counts, even after controlling for prior values of CD4 cell count, viral load, and treatment. Higher BMI and increases in BMI are associated with a decreased risk of HIV progression.

Continuity of medical care and risk of incarceration in HIV-positive and high-risk HIV-negative women.

OBJECTIVES: Incarceration rates in the United States have tripled over the past two decades and have increased even more rapidly among women than men. To identify risk factors that predict incarceration in HIV-positive (HIV+) and high-risk HIV-negative (HIV-) women and to evaluate the association between continuity of medical care and risk of incarceration, this analysis was conducted. METHODS: This was a prospective cohort study of HIV+ and high-risk HIV- women enrolled between April 1993 and January 1995 at four urban centers: Providence, Rhode Island; New York, New York; Baltimore, Maryland; and Detroit, Michigan. The HIV Epidemiology Research (HER) Study enrolled 871 HIV+ and 439 high-risk HIV- innercity women between the ages of 16 and 55 years. All participants had a history of injection drug use or high-risk sexual behavior. Interviews, including questions on continuity of medical care and incarceration, were administered at baseline and 6 and 12 months after enrollment. Any incarceration in the 1-year period following enrollment was the main outcome measure. Continuity of care was measured as having seen one healthcare provider for at least 2 years, having received medical care from one usual physician or clinic, and having obtained medical care in a primary care setting as opposed to an emergency room or drug treatment center. RESULTS: Twelve percent of women were incarcerated within 1 year postenrollment. Factors associated with incarceration included recent drug use, prior incarceration, lack of college education, engaging in sex for drugs or money, and having multiple unmet basic needs at the time of enrollment in the study. Continuity of care with a single healthcare provider for more than 2 years prior to enrollment in the study was associated with decreased rates of incarceration even after adjusting for possible confounding factors (OR = 0.67, 95% CI = 0.48 - 0.92). HIV serostatus did not correlate with incarceration. CONCLUSIONS: History of prior incarceration and recent drug use were associated with increased risk of incarceration. Continuity of medical care by a single healthcare provider was associated with decreased likelihood of incarceration, suggesting that the provider may play an important role in designing interventions to prevent incarceration in this high-risk population.

Evaluation of possible effects of continued drug use on HIV progression among women.

Data from a prospective, multi-centred study of HIV infection in women (HIV Epidemiology Research Study [HERS]) was analysed to investigate the effect of continued injection drug use behaviours on progression to AIDS. All women enrolled in the HERS had at enrollment and at six-month intervals, a face-to-face interview which included specific injection drug use, a physical exam, and specimen collection that included T-cell subset analysis and HIV plasma RNA detection. Six hundred and thirty-nine HIV-infected women contributed 3021 person years of observation during 7.25 years of follow-up, and 299 of these women progressed to AIDS (46.8%). In multivariable analysis, there was no significantly increased risk of progression to AIDS for women reporting pre-baseline injection drug use [hazard ratio (HR)=1.07 (0.78, 1.47)] or reported injection drug use during follow-up [HR=0.89 (0.66, 1.21)] compared with never injecting. In a separate multivariable-model, comparing women who reported no injection in past six months to active injection drug users, the frequency of injection during the previous six months measured by daily injection [HR=0.97 (0.61, 1.55)] or less than daily injection [HR=0.84 (0.54, 1.33)] was not associated with progression to AIDS. Being in drug treatment was independently associated with a slower progression to AIDS [HR=0.41 (0.28, 0.59)]. Neither injection drug use, nor frequency of injection drug use was associated with progression to AIDS among HIV infected women. Initiation of antiretroviral therapy among drug users should be based on readiness for treatment rather than concern about faster progression.

Integrating health care for women diagnosed with HIV infection, substance abuse, and mental illness in Detroit, Michigan.

This article describes the evolution of Personalized Nursing, a comprehensive nursing practice model of care. Findings from several nursing research studies contributed to the development of Personalized Nursing. The model includes a practice model of the art of nursing care based on nursing theory and a specific nursing process that directs nursing care delivery. The process of care delivery includes location of hard-to-reach clients; linkage to health care providers; integration of care among providers for clients diagnosed with HIV, mental illness, and substance abuse; and strategies to promote retention in health care. Use of Personalized Nursing is designed to assist clients to improve their well-being and increase positive health-related behaviors. Personalized Nursing has been used in urban landscapes to serve multiply diagnosed clients at risk for HIV infection. The model is currently being used in a study targeting multiply diagnosed women who are lost to follow-up from medical care.