Depression and all-cause mortality risk in HIV-infected and HIV-uninfected US veterans: a cohort study.

OBJECTIVES: The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. METHODS: Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. RESULTS: Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. CONCLUSIONS: Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.

The impact of prescribed opioids on CD4 cell count recovery among HIV-infected patients newly initiating antiretroviral therapy.

OBJECTIVES: Certain prescribed opioids have immunosuppressive properties, yet their impact on clinically relevant outcomes, including antiretroviral therapy (ART) response among HIV-infected patients, remains understudied. METHODS: Using the Veterans Aging Cohort Study data, we conducted a longitudinal analysis of 4358 HIV-infected patients initiating ART between 2002 and 2010 and then followed them for 24 months. The primary independent variable was prescribed opioid duration, categorized using pharmacy data as none prescribed, short-term (< 90 days) and long-term (≥ 90 days). Outcomes included CD4 cell count over time. Analyses adjusted for demographics, comorbid conditions, ART type and year of initiation, and overall disease severity [ascertained with the Veterans Aging Cohort Study (VACS) Index]. Sensitivity analyses examined whether effects varied according to baseline CD4 cell count, achievement of viral load suppression, and opioid properties (i.e. dose and known immunosuppressive properties). RESULTS: Compared to those with none, patients with short-term opioids had a similar increase in CD4 cell count (mean rise per year: 74 vs. 68 cells/µL; P = 0.11), as did those with long-term prescribed opioids (mean rise per year: 74 vs. 75 cells/µL; P = 0.98). In sensitivity analysis, compared with no opioids, the effects of short-term prescribed opioids were statistically significant among those with a baseline CD4 cell count ≥ 500 cells/µL (mean rise per year: 52 cells/µL for no opioids vs. 20 cells/µL for short-term opioids; P = 0.04); findings were otherwise unchanged. CONCLUSIONS: Despite immunosuppressive properties intrinsic to opioids, prescribed opioids appeared to have no effect on CD4 cell counts over 24 months among HIV-infected patients initiating ART.

Impact of defined clinical population and missing data on temporal trends in HIV viral load estimation within a health care system.

OBJECTIVES: Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS: We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS: The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS: The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

Prevalence and correlates of obstructive sleep apnoea among patients with and without HIV infection.

OBJECTIVES: In HIV-uninfected populations, obstructive sleep apnoea (OSA) is commonly associated with cardiovascular disease, metabolic syndrome, and cognitive impairment. These comorbidities are common in HIV-infected patients, but there are scarce data regarding OSA in HIV-infected patients. Therefore, we examined the prevalence and correlates of OSA in a cohort of HIV-infected and uninfected patients. METHODS: An observational cohort study was carried out. Electronic medical record and self-report data were examined in patients enrolled in the Veterans Aging Cohort Study (VACS) between 2002 and 2008 and followed until 2010. The primary outcome was OSA diagnosis, determined using International Classification of Diseases, 9th edition (ICD-9) codes, in HIV-infected compared with uninfected individuals. We used regression analyses to determine the association between OSA diagnosis, symptoms and comorbidities in adjusted models. RESULTS: Of 3683 HIV-infected and 3641 uninfected patients, 143 (3.9%) and 453 (12.4%) had a diagnosis of OSA (p<0.0001), respectively. HIV-infected patients were more likely to report symptoms associated with OSA such as tiredness and fatigue. Compared with uninfected patients with OSA, HIV-infected patients with OSA were younger, had lower body mass indexes (BMIs), and were less likely to have hypertension. In models adjusting for these traditional OSA risk factors, HIV infection was associated with markedly reduced odds of OSA diagnosis (odds ratio 0.48; 95% confidence interval 0.39-0.60). CONCLUSIONS: HIV-infected patients are less likely to receive a diagnosis of OSA. Future studies are needed to determine whether the lower prevalence of OSA diagnoses in HIV-infected patients is attributable to decreased screening and detection or to a truly decreased likelihood of OSA in the setting of HIV infection.

Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers.

BACKGROUND: As those with HIV infection live longer, 'non-AIDS' condition associated with immunodeficiency and chronic inflammation are more common. We ask whether 'non-HIV' biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART). METHODS: Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining conditions); 'non-HIV' biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data. RESULTS: Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle-aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and 'non-HIV' markers were associated with each other (P < 0.0001) and discriminated mortality (C statistics 0.68-0.73); when combined, discrimination improved (P < 0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30-day C statistic 0.86, 95% confidence interval (CI) 0.80-0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72-0.74). Results were robust to adjustment for missing data. CONCLUSIONS: When added to HIV biomarkers, 'non-HIV' biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research.

Emergency department time for evaluation of patients discharged with a diagnosis of renal colic: unenhanced helical computed tomography versus intravenous urography.

The objective of this study was to determine whether patients discharged from the Emergency Department (ED) with a proven diagnosis of renal colic require less total evaluation and treatment time if unenhanced helical computed tomography (CT) rather than intravenous urography (IVU) was the diagnostic imaging study used. A retrospective review was undertaken of the medical records of 98 consecutive patients with a final diagnosis of urolithiasis or renal colic evaluated with an unenhanced helical CT scan or an IVU between January 1, 1999, and December 31, 1999. All patients were managed by Emergency Physicians and discharged from the ED. The time the patient was brought to the treatment area, the time the imaging study was ordered, and the time the patient was discharged were recorded. There were 75 patients evaluated with CT scan and 23 patients with an IVU. Patients who underwent unenhanced helical CT scan were in the ED for a mean time of 291 min [95% confidence interval (CI) 266-316] and those who had an IVU were in the ED for an average of 410 min (95% CI 340-481). Use of unenhanced helical CT scan was associated with less total time in the ED compared to IVU for patients with renal colic by a significant mean of 119 min. It is concluded that ED evaluation and treatment time of patients ultimately discharged with a proven diagnosis of renal colic is significantly less when evaluated with unenhanced helical CT scan compared to IVU.

A prospective randomized trial of four three-drug regimens in the treatment of disseminated Mycobacterium avium complex disease in AIDS patients: excess mortality associated with high-dose clarithromycin. Terry Beirn Community Programs for Clinical Research on AIDS.

The optimal regimen for treatment of Mycobacterium avium complex (MAC) disease has not been established. Eighty-five AIDS patients with disseminated MAC disease were randomized to receive a three-drug regimen of clarithromycin, rifabutin or clofazimine, and ethambutol. Two dosages of clarithromycin, 500 or 1,000 mg twice daily (b.i.d.), were compared. The Data and Safety Monitoring Board recommended discontinuation of the clarithromycin dosage comparison and continuation of the rifabutin vs. clofazimine comparison. After a mean follow-up of 4.5 months, 10 (22%) of 45 patients receiving clarithromycin at 500 mg b.i.d. had died (70 deaths per 100 person-years) compared with 17 (43%) of 40 patients receiving clarithromycin at 1,000 mg b.i.d. (158 deaths per 100 person-years) (relative risk, 2.43; 95% confidence interval, 1.11-5.34; P = .02). After 10.4 months, 20 (49%) of 41 patients receiving rifabutin had died (81 deaths per 100 person-years) compared with 23 (52%) of 44 patients receiving clofazimine (94 deaths per 100 person-years) (relative risk, 1.20; 95% confidence interval, 0.65-2.19; P = .56). Bacteriologic outcomes were similar among treatment groups. In treating MAC disease in AIDS patients, the maximum dose of clarithromycin should be 500 mg b.i.d.

An uncommon Helicobacter isolate from blood: evidence of a group of Helicobacter spp. pathogenic in AIDS patients.

An unusual Helicobacter sp. was isolated from the blood of a human immunodeficiency virus (HIV)-infected patient. This organism had spiral morphology, with single amphitrichous flagella, and was negative for hippurate hydrolysis, production of urease, and reduction of nitrate. 16S rRNA gene sequence analysis verified that the isolate was a species of Helicobacter, most closely related to an undescribed Helicobacter-like isolate from Vancouver, British Columbia, Canada, and to Helicobacter westmeadii, a recently described species from Australia. Both organisms had also been isolated from the blood of HIV-infected patients. These blood isolates, along with Helicobacter cinaedi, form a cluster of closely related Helicobacter spp. that may represent an emerging group of pathogens in immunocompromised patients.

Randomized, controlled trial of caloric supplements in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: To compare the efficacy of three nutritional regimens in the prevention of weight loss. DESIGN: A three-arm randomized controlled trial with primary outcome measure percent change in weight over four months. PATIENTS: A total of 536 patients with CD4 count <200 cells/mm3 and stable weight, defined as <5% weight loss as determined by a weight measurement 3 to 6 months before randomization were recruited at fourteen administrative units in the United States, each unit consisting of multiple primary care sites. INTERVENTION: The three arms were 500 kcal daily of caloric supplement with peptides and medium-chain triglycerides plus a multivitamin and mineral supplement, 500 kcal of a caloric supplement with whole protein and long-chain triglycerides plus a multivitamin and mineral supplement, and a multivitamin and mineral supplement only. RESULTS: There were no significant differences among the three regimens in the percent change in weight (p = .74) and body cell mass (p = .63). On average, 65% of the recommended 500 kcal/day of caloric supplements containing peptides with medium-chain triglycerides and 82% of the 500 kcal/day of the caloric supplement containing whole protein and long-chain triglycerides were consumed. CONCLUSIONS: Caloric supplements do not promote increases in average weight or body cell mass in weight-stable, HIV-infected adults beyond that offered by a multivitamin and mineral supplement.

Weight loss as a predictor of survival and disease progression in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS.

Severe weight loss in HIV is associated with decreased length of survival. It is unclear whether mild weight loss is associated with an increased risk of death or opportunistic complications of HIV. Participants in four interventional studies (n = 2382) conducted by a community-based clinical trials network were evaluated for percentage change in weight during their first 4 months in the study. Proportional hazards models were performed for the occurrence of opportunistic complications and death subsequent to the 4-month visit. The relative risk of death and opportunistic complications for those with 5% to 10% weight loss over 4 months was 2.22 (p < .001) and 1.89 (p < .001), respectively, and 1.26 (p < .01) and 1.19 (p < .01) among those who lost 0% to 5% of their body weight, respectively, when compared with those with no weight loss. Among those who lost 5% to 10% of their body weight, the relative risk of individual opportunistic complications increased significantly, including Pneumocystis carinii pneumonia (PCP) (1.61; p < .01), cytomegalovirus (CMV) (2.33; p < .001), and Mycobacterium avium complex (MAC) (1.81; p < .01). As little as 5%t weight loss over a 4-month period is associated with increased risk of death and opportunistic complications in HIV. A weight loss of 5% to 10% is also associated with an increased risk of individual opportunistic complications.

Cat scratch disease and acquired immunodeficiency disease: diagnosis by transmission electron microscopy.

A 33-year-old, homosexual, cat-owning, African-American man with human immunodeficiency virus infection by positive serologic tests and acquired immunodeficiency syndrome by CD4 lymphocyte count alone (39 cells/mL) presented with a one-year history of intermittent fever, weight loss, and generalized lymphadenopathy. A malignant lymphoma was suspected clinically. Light microscopic study of a left inguinal lymph node biopsy specimen revealed effacement of the lymph node architecture by a diffuse infiltrate of large, atypical reticulum cells, loose, patchy granulomatous inflammation, diffuse hyaline fibrosis, diffusely proliferated blood vessels, and multifocal degeneration and necrosis. Lymph follicles were absent and lymphocytes were moderately depleted. Microorganisms were not seen in lymph node sections stained with special histochemical stains (including the Warthin-Starry stain). These light microscopic changes were considered suggestive of a malignant lymphoma, especially Hodgkin's disease. The diagnosis of cat scratch disease (CSD) became apparent only after transmission electron microscopic study of the lymph node revealed clusters of small, pleomorphic bacteria in degenerated collagenous tissue and in blood vessel walls. This case illustrates the value of transmission electron microscopy in making the diagnosis of CSD, especially when light microscopic changes are superimposed on those of late human immunodeficiency virus infection of the lymph node.

Disseminated toxoplasmosis and acquired immunodeficiency syndrome: diagnosis by transmission electron microscopy.

A 43-year-old, bisexual, black man with acquired immunodeficiency syndrome (AIDS), detected by CD4 lymphocyte criteria alone, presented with low-grade fever, chills, malaise, and watery diarrhea of 2 days' duration. Over the next 5 days, he developed a fulminant septicemia-like illness with progressive hypotension, disseminated intravascular coagulation, and very high serum lactic acid dehydrogenase (2,150 U/L) and serum creatine phosphokinase (5,395 U/L) levels, and died. The cause of this illness was not clinically apparent. A bone marrow biopsy performed on the day of his death revealed intracytoplasmic clusters of 3 microns long, oval, basophilic organisms, the exact nature of which was not evident by light microscopy. The diagnosis of disseminated toxoplasmosis (DT) was made only after electron microscopic study of the bone marrow revealed organisms with features typical of Toxoplasma gondii tachyzoites. These features included a multilayered pellicle, a pointed anterior end containing a conoid, up to nine rhoptries, sparse micronemes, and a posterior end containing a nucleus. Some of the organisms had divided by internal budding or endodyogeny. This case illustrates the value of transmission electron microscopy in making the diagnosis of DT.

Nosocomial outbreak of respiratory tract colonization with Mycobacterium fortuitum: demonstration of the usefulness of pulsed-field gel electrophoresis in an epidemiologic investigation.

Between August 1989 and January 1990, 16 patients on an alcoholism rehabilitation ward (ARW) developed positive sputum cultures for Mycobacterium fortuitum. During a 2-wk surveillance period, six of 43 ARW patients but none of 20 staff members had positive sputum cultures. In addition, none of 54 patients and staff on an adjacent ward sharing the same ice machine and water supply had positive cultures, and none of 92 acid-fast bacilli cultures performed on all sputum specimens from all other inpatient sources during the same 2-wk period were positive. The only exposure factor common to all cases was the use of one or both of the ward showers. Compared with 36 ARW control patients, cases were more likely to report clinical criteria for chronic bronchitis (odds ratio, 6.6; 95% confidence interval, 1.5 to 28.6; p = 0.02). Using phenotype analysis, plasmid profiles, and pulsed-field gel electrophoresis of large genomic DNA restriction enzyme fragments, the 16 case isolates were found to be identical. This strain of M. fortuitum was also cultured from a tap connected to the water line supplying the ARW showers, but not from the showers themselves. No further cases were identified after the showers were disconnected and decontaminated. To our knowledge, this is the first clinical use of pulsed-field gel electrophoresis for genetic comparison of mycobacterial strains. It demonstrates the important potential of this technique for studying the epidemiology of mycobacterial infections. Showers should be considered a possible source of nosocomial respiratory tract colonization with M. fortuitum.