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Objective: To assess the associations between nucleoside reverse transcriptase inhibitors (NRTIs) and change in lipid levels among a large cohort of HIV-infected patients in routine clinical care initiating their first potent antiretroviral regimen. Design: Longitudinal observational cohort study from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. Methods: We used generalized estimating equations to examine the association between NRTIs and lipids accounting for within-patient correlations between repeated measures and key clinical and demographic characteristics including other antiretroviral medications. Results: Among 2267 individuals who started their first antiretroviral regimen, tenofovir with emtricitabine or lamivudine was associated with lower levels for total cholesterol, low-density lipoprotein (LDL), triglycerides, non-high-density lipoprotein (HDL), and HDL, compared with other NRTI pairs in adjusted analyses. LDL levels were highest among patients receiving didanosine/lamivudine. Triglyceride levels were highest in stavudine/lamivudine users. HDL levels were highest among patients receiving didanosine/stavudine. Hepatitis C infection and younger age were also associated with lower lipid levels. Conclusion: We found clinically important heterogeneity within the NRTI class of antiretroviral medications regarding their effect on lipid levels over time. Although the lipid profile of tenofovir with emtricitabine or lamivudine appeared to be less proatherogenic in this large longitudinal study of HIV-infected patients in routine clinical care, there was no association with beneficial HDL levels. In general, the change in lipid levels associated with most antiretroviral agents, particularly those NRTI combinations currently in common use, are relatively modest. Additional studies are needed to understand the long-term implications of these findings on cardiovascular disease risk.

Little is known about the psychometric properties of depression instruments among persons infected with HIV. We analyzed data from a large sample of patients in usual care in two US cities (n=1467) using the 9-item Patient Health Questionnaire from the PRIME-MD (the PHQ-9). The PHQ-9 had curvilinear scaling properties and varying levels of measurement precision along the continuum of depression measured by the instrument. In our cohort, the scale showed a prominent floor effect and a distribution of scores across depression severity levels. Three items had differential item functioning (DIF) with respect to race (African-American vs. white); two had DIF with respect to sex, and one had DIF with respect to age. There was minimal individual-level DIF impact. Twenty percent of the difference in mean depression levels between African-Americans and whites was due to DIF. While standard scores for the PHQ-9 may be appropriate for use with individual HIV-infected patients in cross-sectional settings, these results suggest that investigations of depression across groups and within patients across time may require a more sophisticated analytic framework.

Background. Human immunodeficiency virus (HIV) and AIDS continue to be associated with an underrecognized risk for suicidal ideation, attempted suicide, and completed suicide. Suicidal ideation represents an important predictor for subsequent attempted and completed suicide. We sought to implement routine screening of suicidal ideation and associated conditions using computerized patient-reported outcome (PRO) assessments. Methods. Two geographically distinct academic HIV primary care clinics enrolled patients who attended scheduled visits from December 2005 through February 2009. Touch-screen, computer-based PRO assessments were implemented into routine clinical care. Substance abuse, alcohol consumption, depression, and anxiety were assessed. The 9-item Patient Health Questionnaire assesses the frequency of suicidal ideation in the preceding 2 weeks. A response of “nearly every day” triggered an automated page to predetermined clinic personnel, who completed more detailed self-harm assessments. Results. Overall, 1216 patients (740 from the University of Alabama at Birmingham and 476 from the University of Washington) completed the initial PRO assessment during the study period. Patients were predominantly white (646 [53%]) and male (959 [79%]), with a mean age (� standard deviation) of years. Among surveyed 44 � 10 patients, 170 (14%) endorsed some level of suicidal ideation, whereas 33 (3%) admitted suicidal ideation nearly every day. In multivariable analysis, suicidal ideation risk was lower with advancing age (odds ratio [OR], 0.74 per 10 years; 95% confidence interval [CI], 0.58‐0.96) and was increased with current substance abuse (OR, 1.88; 95% CI, 1.03‐3.44) and more-severe depression (OR, 3.91 for moderate depression [95% CI, 2.12‐7.22] and 25.55 for severe depression [95% CI, 12.73‐51.30]). Discussion. Suicidal ideation was associated with current substance abuse and depression. The use of novel technologies to incorporate routine self-reported screening for suicidal ideation and other health domains allows for timely detection and intervention for this life-threatening condition.

Immunization with hepatitis B (HBV) vaccine is recommended for all HIV-infected individuals without immunity to HBV. This patient population, however, has relatively poor HBV vaccine responses. Factors associated with this impaired HBV vaccine response in HIV-infected individuals may include older age, uncontrolled HIV replication, and low nadir CD4 cell count. Postvaccination testing for HBV surface antibody is recommended and vaccine non-responders should undergo repeat immunization with a full series. The benefit of double dosage, the appropriate strategy for HIV-infected patients with isolated HBV core antibody and the timing and number of vaccinations in persons with advanced immunosuppression on highly active antiretroviral therapy remain controversial areas.

Objective Lipoatrophy and lipohypertrophy are associated with metabolic abnormalities, but little is known about their impact on hypertension. We conducted this study to determine the associations of lipoatrophy and lipohypertrophy with hypertension. Methods A cross-sectional study of HIV-infected patients who completed a self-report body morphology assessment was performed. We defined hypertension as a clinical diagnosis, or a mean systolic blood pressure (BP)>140 mmHg or diastolic BP>90 mmHg in the previous 6 months. We used logistic regression to examine the association between hypertension and body morphology. Results Among 347 patients, there were 2278 BP readings in 6 months. In adjusted analyses, patients with moderate lipoatrophy [odds ratio (OR) 4.3; P=0.03] or moderate lipohypertrophy (OR 4.3; P=0.006) had four times the odds, and patients with mild lipohypertrophy (OR 2.3; P=0.03) had twice the odds of having hypertension compared with patients without changes. We hypothesized that the impact of lipohypertrophy on hypertension was mediated, in part, through body mass index (BMI). When BMI was included in the analysis, increased BMI was significantly associated with hypertension (OR=1.1; P

BACKGROUND The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P

Information regarding the prevalence of mental illness and substance use among HIV-infected patients and the effect of these problems on HIV treatment is needed. We conducted an observational study of patients in the University of Washington (UW) HIV Cohort to determine prevalence rates for mental illness and substance use. Cox regression analyses were used to examine the relationship between mental illness and substance use, pharmacologic treatment for depression/anxiety, and initiation of highly active antiretroviral therapy (HAART) within 9 months of becoming eligible for HAART. Among 1774 patients in the UW HIV cohort during 2004, 63% had a mental illness (including mood, anxiety, psychotic, or personality disorders), 45% had a substance use disorder, and 38% had both. There were 278 patients who met criteria for HAART eligibility. After controlling for other factors, patients with depression and/or anxiety were significantly less likely to initiate HAART compared with patients without a mental illness (hazard ratio [HR] 0.4, p = 0.02). However, patients with depression/anxiety who received antidepressant/antianxiety medications were equally likely to initiate HAART as patients without a mental illness (HR 0.9, p = 0.5). We found that patients with mental illness or substance use disorders receive HAART at lower CD4+ cell counts and higher HIV-1 RNA levels than patients without these disorders. However, HAART initiation among patients who receive treatment for depression/anxiety is associated with no delay. Screening for these disorders in primary care settings and access to appropriate treatment are increasingly important components of providing care to HIV-infected patients.

Highly active antiretroviral therapy (HAART) delays disease progression and death. However, the treatments incompletely control HIV replication, only partially restore immune function, have significant shortand long-term toxicities, and eventually fail in many patients with consequent development of HIV drug resistance. Thus, there is increasing need for information to guide HIV-infected patients and their providers in making decisions regarding optimal use of antiretroviral therapies. Although clinical trials provide valuable information about efficacy and side effects of antiretroviral treatment, they have limited size, duration and power to detect effects on clinical outcomes, focusing instead on surrogate endpoints such as virologic failure, treatment discontinuation or composite outcome measures. Outside the clinical trial setting, there is tremendous heterogeneity among HIV-infected patients. The prevalence and impact of important health conditions such as hepatitis C virus (HCV) co-infection, mental illness and substance abuse likely contribute to increased toxicity and decreased clinical effectiveness of HAART regimens among the broader spectrum of patients treated in routine care. Cohorts with significant diversity in HIV disease severity, comorbidities and demographic distributions are required to provide information regarding long-term outcomes and complications of HIV infection in the modern HAART era. The Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) was created to better define the relationship between patient and treatment factors and long-term clinical outcomes among HIV-infected patients in the HAART era. The CFARs are a national network of centres of excellence for HIV care and research established by the National Institutes of Health (NIH) whose mission is to support a multi-disciplinary environment for basic, clinical, epidemiologic, behavioural and translational research in the prevention, detection and treatment of HIV infection and AIDS. There are 19 CFARs located at academic and research institutions throughout the United States. The objective of the CNICS project is to integrate clinical data from the large and diverse population of HIV-infected persons receiving care at CFAR sites to investigate questions related to HIV disease management that cannot be readily addressed through traditional randomized controlled clinical trials and other cohort studies. Investigators with expertise in basic, clinical, translational and epidemiologic research, in addition to medical informatics, are collaborating on the CNICS project. The potential to build a comprehensive clinical data repository for HIV disease was greatly advanced by the work of CFAR investigators at the participating CNICS sites who had instituted point-of-care electronic medical record systems (EMRs) with the dual purpose of providing real-time clinical information to facilitate the delivery of HIV care and capturing standardized clinical data to support populationbased HIV research. The initial four CNICS sites were Case Western Reserve University, University of * Corresponding author. Center for AIDS Research, University of Washington, 325 9th Ave, MS 359931, Seattle, WA 98104, USA. E-mail: kitahata@u.washington.edu 1 Department of Medicine, University of Washington, Seattle, 98195, USA. 2 Department of Medicine, Case Western Reserve University, Cleveland, 44106, USA. 3 Department of Medicine, University of California, San Diego, 92110, USA. 4 Department of Medicine, Harvard University, Boston, 02115, USA. 5 Department of Medicine, Johns Hopkins University, Baltimore, 21218, USA. 6 Department of Medicine, University of Alabama, Birmingham, 35209, USA. 7 Department of Medicine, University of California, San Francisco, 94143, USA. Published by Oxford University Press on behalf of the International Epidemiological Association

OBJECTIVE To examine the effect of antiretroviral agents and clinical factors on the development of tenofovir-associated kidney dysfunction. METHODS Observational cohort study of HIV-infected patients receiving tenofovir in an HIV clinic population. Patients' kidney function prior to initiating and while receiving tenofovir was evaluated in relation to other antiretroviral medications and demographic and clinical characteristics. Decline in kidney function was assessed by the glomerular filtration rate (GFR) as estimated by the Cockcroft-Gault (CG) equation, which incorporates weight. Logistic regression analysis was used to examine factors associated with GFR of > 90, 60-90, 30-60, and < 30 ml/min per 1.73 m(2) while on tenofovir. Secondary analyses used the simplified Modification of Diet in Renal Disease (MDRD) equation. RESULTS Among the 445 patients initiating tenofovir, 51 (11%) developed a decline in kidney function. In multivariate analysis, there was a significant association between decline in kidney function and concurrent use of amprenavir [odds ratio (OR) 3.6; P = 0.045] and didanosine (OR, 3.1; P = 0.006), age over 50 years (OR, 4.4; P = 0.03), and lower baseline weight (OR, 0.95/kg; P < 0.001). Patients identified with kidney dysfunction by the MDRD equation did not fully overlap with those identified by the CG equation. CONCLUSIONS Didanosine and amprenavir use, increased age, and lower baseline weight were significantly associated with risk for kidney dysfunction among patients receiving tenofovir. GFR results using the MDRD equation were inconsistent with those using CG, which highlights the impact of including weight in the estimation of GFR among HIV-infected patients.

Objective: New onset diabetes mellitus type 2 is increasing among HIV-infected patients in the era of potent antiretroviral therapy. Accurately identifying HIV-infected patients with a diagnosis of diabetes in electronic medical record systems will facilitate the study of patients with this disease. Study Design And Setting: We examined electronic medical record data for all patients who initiated care at an HIV clinic between 1/1/1997 and 12/31/2001 to identify potential cases of diabetes. Case identification methods included clinician-coded diagnoses, medications, and HbA1c and glucose levels. Diabetes diagnoses were verified by clinician documentation in an electronic medical record progress note. Test characteristics of each case identification method were calculated. Results: 53 cases of diabetes were identified among the cohort of 1441 patients. Use of clinician-coded diagnoses alone or combined with other methods was the most sensitive method for identifying diabetes cases. Clinician-coded diagnoses were also the best method as assessed by standard receiver operator characteristic plots. A significant attenuation of odds ratios for associations with diabetes were found for case identification methods with imperfect specificity such as serum glucose levels. Conclusions: This study demonstrates that electronic medical record data can be used to accurately identify HIV-infected patients with diabetes. The optimal method applied will depend on the goals of a particular study.

This unique report describes a fatal case of immune reconstitution syndrome associated with Kaposi's sarcoma (KS). This case also illustrates the possibility of cryptic visceral KS with minimal cutaneous disease, as well as the potential for differential responses of cutaneous and visceral KS to treatment.

1. Little interest or pleasure in doing things. 2. Feeling down, depressed, or hopeless. 3. Trouble falling or staying asleep, or sleeping too much. 4. Feeling tired or having little energy. 5. Poor appetite or overeating. 6. Feeling bad about yourself—or that you are a failure or have let yourself or your family down. 7. Trouble concentrating on things, such as reading the newspaper or watching television. 8. Moving or speaking so slowly that other people could have noticed. Or the opposite—being so fidgety or restless that you have been moving around a lot more than usual. 9. Thoughts that you would be better off dead, or of hurting yourself in some way.

In the 30 years since the HIV epidemic was recognized in the United States, remarkable advances in treatment have turned a rapidly fatal disease into a chronic illness for persons who are aware of their infection and can access effective care (1, 2). The Centers for Disease Control and Prevention (CDC) estimates that 1.2 million persons live with HIV in the United States (3). The estimated annual rate of new HIV infections between 2006 and 2009 ranged from 19.0 to 22.5 per 100 000 population (approximately 47 800 to 56 000 new infections per year), with most occurring among men who have sex with men (MSM) and African Americans (4). A central component of the National HIV/AIDS Strategy (5) is to monitor the health of the growing number of Americans living with HIV infection who receive HIV treatment. Although seemingly simple, such monitoring is actually a substantial epidemiologic challenge because of the complexity of the U.S. health care system. Many of the studies that have reported trends in the clinical outcomes of persons receiving HIV care (6–12) have been limited to discrete populations, and their findings have not been generalizable to all HIV-infected Americans. Two projects have been specifically designed to be nationally representative. The HCSUS (HIV Cost and Services Utilization Study) (13, 14) enrolled a national probability sample of HIV-infected adults receiving care from 1996 to 1998. Although useful a decade ago, data from this population no longer reflect the substantial improvements in HIV care in the past 14 years. The Medicapl Monitoring Project is an ongoing CDC-sponsored, multisite, supplemental national surveillance project designed to capture contemporary data about behaviors, medical care, and health status of HIV-infected adults in the United States through annual cross-sectional surveys (15). Data are compiled from the medical records of persons in care, who are selected through a 3-stage probability sampling scheme designed to produce a representative sample. Participants in the Medical Monitoring Project are not followed longitudinally, which limits its capacity to evaluate such associations as those between treatment and clinical outcomes, including survival. Conversely, even very large longitudinal cohort studies are not perfectly representative. Neither longitudinal cohort studies nor cross-sectional probability surveys alone can provide the most complete and accurate picture of HIV-infected persons in care; however, by addressing limitations of the other, together they provide highly useful, complementary information. The NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) is the continent’s largest collaboration of longitudinal HIV cohort studies and has compiled clinical data from more than 100 clinical sites in the United States and Canada since 2005 (16). In this analysis, we assessed the extent to which attributes of persons receiving HIV care in an NA-ACCORD–participating U.S. clinical cohort are similar to those of persons living with HIV in the United States (PLWH-US) who are reported to the CDC’s HARS (Center’s for Disease Control’s HIV/AIDS Reporting System). We then examined the following illustrative and linked health outcomes among HIV-infected persons in care: trends in prescribed antiretroviral therapy (ART), HIV RNA plasma viral load (HIV VL), and CD4 T-lymphocyte (CD4) cell count at death. Our objective was to investigate the utility of NA-ACCORD for monitoring the U.S. HIV epidemic and for informing the progress made toward achieving the targets of the National HIV/AIDS Strategy.