Uptake and virological outcomes of single- versus multi-tablet antiretroviral regimens among treatment-naïve youth in the HIV Research Network.

OBJECTIVES: Several single-tablet regimens (STRs) are now available and are recommended for first-line antiretroviral therapy (ART); however, STR use for youth with HIV (YHIV) has not been systematically studied. We examined the characteristics associated with initiation of STRs versus multi-tablet regimens (MTRs) and the virological outcomes for youth with nonperinatally acquired HIV (nPHIV). METHODS: A retrospective cohort study of nPHIV youth aged 13-24 years initiating ART between 2006 and 2014 at 18 US HIV clinical sites in the HIV Research Network was performed. The outcomes measured were initiation of STRs versus MTRs, virological suppression (VS) at 12 months, and time to VS. Demographic and clinical factors associated with initiation of STR versus MTR ART and VS (< 400 HIV-1 RNA copies/mL) at 12 months after initiation were assessed using multivariable logistic regression. Cox proportional hazards regression was used to assess VS within the first year. RESULTS: Of 987 youth, 67% initiated STRs. Of the 589 who had viral load data at 1 year, 84% of those on STRs versus 67% of those on MTRs achieved VS (P < 0.01). VS was associated with STR use [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.01-2.58], white (AOR 2.41; 95% CI 1.13-5.13) or Hispanic (AOR 2.38; 95% CI 1.32-4.27) race/ethnicity, and baseline CD4 count 351-500 cells/µL (AOR 1.94; 95% CI 1.18-3.19) and > 500 cells/µL (AOR 1.76; 95% CI 1.0-3.10). STR use was not associated with a shorter time to VS compared with MTR use [hazard ratio (HR) 1.07; 95% CI 0.90-1.28]. CONCLUSIONS: Use of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV.

Thirty-day hospital readmissions for adults with and without HIV infection.

OBJECTIVES: Risk-adjusted 30-day hospital readmission rate is a commonly used benchmark for hospital quality of care and for Medicare reimbursement. Persons living with HIV (PLWH) may have high readmission rates. This study compared 30-day readmission rates by HIV status in a multi-state sample with planned subgroup comparisons by insurance and diagnostic categories. METHODS: Data for all acute care, nonmilitary hospitalizations in nine states in 2011 were obtained from the Healthcare Costs and Utilization Project. The primary outcome was readmission for any cause within 30 days of hospital discharge. Factors associated with readmission were evaluated using multivariate logistic regression. RESULTS: A total of 5 484 245 persons, including 33 556 (0.6%) PLWH, had a total of 6 441 695 index hospitalizations, including 45 382 (0.7%) among PLWH. Unadjusted readmission rates for hospitalizations of HIV-uninfected persons and PLWH were 11.2% [95% confidence interval (CI) 11.2, 11.2%] and 19.7% (95% CI 19.3, 20.0%), respectively. After adjustment for age, gender, race, insurance, and diagnostic category, HIV infection was associated with 1.50 (95% CI 1.46, 1.54) times higher odds of readmission. Predicted, adjusted readmission rates were higher for PLWH within every insurance category, including Medicaid [12.9% (95% CI 12.8, 13.0%) and 19.1% (95% CI 18.4, 19.7%) for HIV-uninfected persons and PLWH, respectively] and Medicare [13.2% (95% CI 13.1, 13.3%) and 18.0% (95% CI 17.4, 18.7%), respectively], and within every diagnostic category. CONCLUSIONS: HIV infection is associated with significantly increased readmission risk independent of demographics, insurance, and diagnostic category. The 19.7% 30-day readmission rate may serve as a preliminary benchmark for assessing quality of care of PLWH. Policy-makers may consider adjusting for HIV infection when calculating a hospital's expected readmission rate.

Incidence of and risk factors for bacteraemia in HIV-infected adults in the era of highly active antiretroviral therapy.

BACKGROUND: HIV-infected patients have an increased risk for bacteraemia compared with HIV-negative patients. Few data exist on the incidence of and risk factors for bacteraemia across time in the current era of highly active antiretroviral therapy (HAART). METHODS: We assessed the incidence of bacteraemia among patients followed between 2000 and 2008 at 10 HIV Research Network sites. This large multisite, multistate clinical cohort study collected demographic, clinical and therapeutic data longitudinally. International Statistical Classification of Diseases and Related Health Problems (ICD)-9 codes were examined to identify all cases of in-patient bacteraemia. Logistic regression analysis was used to assess risk factors for bacteraemia and trends over time in the odds of bacteraemia. RESULTS: A total of 39 318 patients were followed for 146 289 person-years (PY). During the study period, there were 2025 episodes of bacteraemia (incidence 13.8 events/1000 PY). The most common bacteraemia diagnosis was 'bacteraemia, not otherwise specified (NOS)' (51%) followed by Staphylococcus aureus (16%) and Streptococcus species (6.5%). In multivariate analysis, the likelihood of bacteraemia was found to have increased in 2005-2008, compared with 2000. Other factors associated with higher odds of bacteraemia included a history of injection drug use (IDU), age ≥ 50 years, Black race and greater immunosuppression. CONCLUSIONS: The likelihood of bacteraemia has risen slightly in recent years. Patients who are Black or have a history of IDU are at higher risk. Further research is needed to identify reasons for this increase and to evaluate programmes designed to reduce the bacteraemia risk.

Estimating the potential pool of HIV-infected deceased organ donors in the United States.

Human immunodeficiency virus (HIV) is no longer a contraindication to transplantation. For HIV-infected patients, HIV-infected deceased donors (HIVDD) could attenuate the organ shortage and waitlist mortality. However, this practice would violate United States federal law. The goal of this study was to estimate the potential impact of legalizing transplantation of HIV-infected organs by quantifying the potential pool of HIVDD. Using Nationwide Inpatient Sample (NIS) data, HIV-infected deaths compatible with donation were enumerated. Using HIV Research Network (HIVRN) data, CD4 count, plasma HIV-1 RNA level, AIDS-defining illnesses and causes of death were examined in potential HIVDD. Using UNOS data, evaluated donors who later demonstrated unanticipated HIV infections were studied. From NIS, a yearly average of 534 (range: 481-652) potential HIVDD were identified, with 63 (range: 39-90) kidney-only, 221 (range: 182-255) liver-only and 250 (range: 182-342) multiorgan donors. From HIVRN, a yearly average of 494 (range: 441-533) potential HIVDD were identified. Additionally, a yearly average of 20 (range: 11-34) donors with unanticipated HIV infection were identified from UNOS. Deceased HIV-infected patients represent a potential of approximately 500-600 donors per year for HIV-infected transplant candidates. In the current era of HIV management, a legal ban on the use of these organs seems unwarranted and likely harmful.

Hospitalization risk following initiation of highly active antiretroviral therapy.

OBJECTIVES: While highly active antiretroviral therapy (HAART) decreases long-term morbidity and mortality, its short-term effect on hospitalization rates is unknown. The primary objective of this study was to determine hospitalization rates over time in the year after HAART initiation for virological responders and nonresponders. METHODS: Hospitalizations among 1327 HAART-naïve subjects in an urban HIV clinic in 1997-2007 were examined before and after HAART initiation. Hospitalization rates were stratified by virological responders (> or =1 log(10) decrease in HIV-1 RNA within 6 months after HAART initiation) and nonresponders. Causes were determined through International Classification of Diseases, 9th Revision (ICD-9) codes and chart review. Multivariate negative binomial regression was used to assess factors associated with hospitalization. RESULTS: During the first 45 days after HAART initiation, the hospitalization rate of responders was similar to their pre-HAART baseline rate [75.1 vs. 78.8/100 person-years (PY)] and to the hospitalization rate of nonresponders during the first 45 days (79.4/100 PY). The hospitalization rate of responders fell significantly between 45 and 90 days after HAART initiation and reached a plateau at approximately 45/100 PY from 91 to 365 days after HAART initiation. Significant decreases were seen in hospitalizations for opportunistic and nonopportunistic infections. CONCLUSIONS: The first substantial clinical benefit from HAART may be realized by 90 days after HAART initiation; providers should keep close vigilance at least until this time.

Emergency department utilization among HIV-infected patients in a multisite multistate study.

OBJECTIVE: The aim of this study was to examine Emergency Department (ED) utilization and clinical and sociodemographic correlates of ED use among HIV-infected patients. METHODS: During 2003, 951 patients participated in face-to-face interviews at 14 HIV clinics in the HIV Research Network. Respondents reported the number of ED visits in the preceding 6 months. Using logistic regression, we identified factors associated with visiting the ED in the last 6 months and admission to the hospital from the ED. RESULTS: Thirty-two per cent of respondents reported at least one ED visit in the last 6 months. In multivariate analysis, any ED use was associated with Medicaid insurance, high levels of pain (the third or fourth quartile), more than seven primary care visits in the last 6 months, current or former illicit drug use, social alcohol use and female gender. Of those who used ED services, 39% reported at least one admission to the hospital. Patients with pain in the highest quartile reported increased admission rates from the ED as did those who made six or seven primary care visits, or more than seven primary care visits vs. three or fewer. CONCLUSIONS: The likelihood of visiting the ED has not diminished since the advent of highly active antiretroviral therapy (HAART). More ED visits are to treat illnesses not related to HIV or injuries than to treat direct sequelae of HIV infection. With the growing prevalence of people living with HIV infection, the numbers of HIV-infected patients visiting the ED may increase, and ED providers need to understand potential complications produced by HIV disease.

The incidence of and risk factors for MRSA bacteraemia in an HIV-infected cohort in the HAART era.

OBJECTIVES: To define the incidence and risk factors for methicillin resistant Staphylococcus aureus (MRSA) bacteraemia in an HIV-infected population. METHODS: From January 1, 2000 to December 31, 2004, we conducted a retrospective cohort study. We identified all cases of Staphylococcus aureus bacteraemia (SAB), including MRSA, among patients enrolled in the Johns Hopkins Hospital out-patient HIV clinic. A conditional logistic regression model was used to identify risk factors for MRSA bacteraemia compared with methicillin-sensitive SAB and no bacteraemia in unmatched (1:1) and matched (1:4) nested case-control analyses, respectively. RESULTS: Of 4607 patients followed for a total of 11 020 person-years (PY) of follow-up, 216 episodes of SAB occurred (incidence: 19.6 cases per 1000 PY), including 94 cases (43.5%) which were methicillin-resistant. The incidence of MRSA bacteraemia increased from 5.3 per 1000 PY in 2000-2001 to 11.9 per 1000 PY in 2003-2004 (P=0.001). Multivariate analysis demonstrated that independent predictors of MRSA bacteraemia (vs. no bacteraemia) were injection drug use (IDU), end-stage renal disease (ESRD) and CD4 count <200 cells/microL. CONCLUSIONS: MRSA bacteraemia was an increasingly common diagnosis in our HIV-infected cohort, especially in patients with history of IDU, low CD4 cell count and ESRD.

Alcohol use among HIV-infected persons in care: results of a multi-site survey.

OBJECTIVE: We sought to determine the prevalence of any alcohol use and hazardous alcohol consumption among HIV-infected individuals engaged in care and to identify factors associated with hazardous alcohol use. METHODS: During 2003, 951 patients were interviewed at 14 HIV primary care sites in the USA. Hazardous drinking was defined as >14 drinks/week or >or=5 drinks/occasion for men and >7 drinks/week or >or=4 drinks/occasion for women. Moderate alcohol use was consumption at less than hazardous levels. We used logistic regression to identify factors associated with any alcohol use and hazardous alcohol use. RESULTS: Forty per cent of the sample reported any alcohol use in the 4 weeks prior to the interview; 11% reported hazardous use. In multivariate regression, male sex [adjusted odds ratio (AOR) 1.52 (95% confidence interval, CI, 1.07-2.16)], a college education (compared toor=500 cells/microL [AOR 2.65 (1.23-5.69)] and illicit drug use [AOR 2.67 (1.48-4.82)] were associated with increased odds of hazardous alcohol use (compared to moderate and none). CONCLUSIONS: Alcohol use is prevalent among HIV-infected individuals and is associated with a variety of socioeconomic and demographic characteristics. Screening for alcohol use should be routine practice in HIV primary care settings.

The impact of illicit drug use and substance abuse treatment on adherence to HAART.

High levels of adherence to highly active antiretroviral therapy (HAART) are essential for virologic suppression and longer survival in patients with HIV. We examined the effects of substance abuse treatment, current versus former substance use, and hazardous/binge drinking on adherence to HAART. During 2003, 659 HIV patients on HAART in primary care were interviewed. Adherence was defined as > or =95% adherence to all antiretroviral medications. Current substance users used illicit drugs and/or hazardous/binge drinking within the past six months, while former users had not used substances for at least six months. Logistic regression analyses of adherence to HAART included demographic, clinical and substance abuse variables. Sixty-seven percent of the sample reported 95% adherence or greater. However, current users (60%) were significantly less likely to be adherent than former (68%) or never users (77%). In multivariate analysis, former users in substance abuse treatment were as adherent to HAART as never users (Adjusted Odds Ratio (AOR)=0.82; p>0.5). In contrast, former users who had not received recent substance abuse treatment were significantly less adherent than never users (AOR=0.61; p=0.05). Current substance users were significantly less adherent than never users, regardless of substance abuse treatment (p<0.01). Substance abuse treatment interacts with current versus former drug use status to affect adherence to HAART. Substance abuse treatment may improve HAART adherence for former substance users.

Use of complementary and alternative medicines among a multistate, multisite cohort of people living with HIV/AIDS.

OBJECTIVE: The aim of the study was to assess the prevalence of and factors associated with use of complementary or alternative medicine (CAM) in a multistate, multisite cohort of HIV-infected patients. METHODS: During 2003, 951 adult patients from 14 sites participated in face-to-face interviews. Patients were asked if they received treatment from any alternative therapist or practitioner in the previous 6 months. Logistic regression was performed to examine associations between demographic and clinical variables and CAM use. RESULTS: The majority of the participants were male (68%) and African American (52%) with a median age of 45 years (range 20-85 years). Sixteen per cent used any CAM in the 6 months prior to the interview. Factors associated with use of CAM were the HIV risk factor injecting drug use [adjusted odds ratio (AOR) 0.51] compared with men who have sex with men (MSM), former drug use (AOR=2.12) compared with never having used drugs, having a college education (AOR=2.43), and visiting a mental health provider (AOR=2.76). CONCLUSIONS: This study demonstrated similar rates of CAM use in the current highly active antiretroviral therapy (HAART) era compared with the pre-HAART era. Factors associated with CAM - such as education, use of mental health services, and MSM risk factor - suggest that CAM use may be associated with heightened awareness regarding the availability of such therapies. Given the potential detrimental interactions of certain types of CAM and HAART, all HIV-infected patients should be screened for use of CAM.

Vancomycin resistance, esp, and strain relatedness: a 1-year study of enterococcal bacteremia.

The prevalence of esp, a gene associated with infection-derived and outbreak strains, in enterococcal blood isolates from 2002 was determined. Fifty-five of 137 (40.1%) Enterococcus faecalis isolates, 30 of 58 (51.7%) E. faecium isolates, 1 of 1 E. raffinosus isolate, 0 of 4 E. gallinarum isolates, and 0 of 1 E. casseliflavus isolate were positive. esp wasn't associated with vancomycin resistance (VR) or clinical service. VR E. faecium isolates were less genetically diverse than vancomycin-susceptible strains. A large cluster of VR isolates, belonging to esp-positive E. faecium, was revealed. These data support the hypothesis that esp and VR may contribute to dissemination of particular clones.

Hospitalization rates in an urban cohort after the introduction of highly active antiretroviral therapy.

OBJECTIVE: Previous studies have shown a decrease in hospitalization rates associated with the introduction of highly active antiretroviral therapy (HAART). To evaluate hospitalization rates and patterns in discharge diagnoses that changed between 1995 and 1998 and to examine risk factors for hospitalization in HIV-positive patients, we conducted a cohort study. PATIENTS AND METHODS: All inpatient hospitalizations of 2,151 HIV-positive patients enrolled in our university-based HIV clinic between January 1, 1994 and December 31, 1998 with a CD4 count within a 6-month calendar semester were examined to evaluate hospitalization rates, discharge diagnoses, and intensive care department use. Negative binomial regression was used to assess the effect of various risk factors on hospitalization. RESULTS: Hospitalization rates decreased between 1995 and 1996 but increased between 1997 and 1998. In multivariate regression, female gender (incidence rate ratio [IRR], 1.45; p <.001), injection drug use (IRR, 1.36; p <.001), and having received no antiretroviral therapy were strong predictors of total hospitalization. White race, low CD4 count, and no antiretroviral treatment were strong predictors of hospitalization for an opportunistic infection. Female gender (IRR, 1.45; p <.001), African-American ethnicity (IRR, 1.22, p =.05), no antiretroviral treatment, and low CD4 counts were predictive of higher hospitalization rates for nonopportunistic infection-related diagnoses. Intensive care department-use was associated with white ethnicity (IRR, 1.86; p =.028), heterosexual transmission of HIV (IRR, 1.90; p =.009), no antiretroviral treatment, and low CD4 count at enrollment. CONCLUSIONS: Our data indicate that hospitalization rates decreased between 1995 and 1997 after introduction of HAART, but that they then increased between 1997 and 1998, particularly for diagnosed nonopportunistic infections. If these trends continue, it indicates that patients may be developing previously unseen comorbidities and that HAART may have reached or exceeded a threshold in its effectiveness in reducing the clinical morbidity that results in hospital admission.

A pilot study of peer review in residency training.

OBJECTIVE: To explore the utility of peer review (review by fellow interns or residents in the firm) as an additional method of evaluation in a university categorical internal medicine residency program. DESIGN/PARTICIPANTS: Senior residents and interns were asked to complete evaluations of interns at the end-of-month ward rotations. MAIN RESULTS: Response rates for senior residents evaluating 16 interns were 70%; for interns evaluating interns, 35%. Analysis of 177 instruments for 16 interns showed high internal consistency in the evaluations. Factor analysis supported a two-dimensional view of clinical competence. Correlations between faculty, senior resident, and intern assessments of interns were good, although varied by domain. CONCLUSIONS: An end-of-year attitude survey found that residents gave high ratings to the value of feedback from peers.

Costs of HIV medical care in the era of highly active antiretroviral therapy.

OBJECTIVES: In the USA, Medicaid is the principal payer of the health care costs of patients with HIV infection. We wished to determine how the costs to Medicaid of patients in Maryland infected with HIV have changed in the setting of highly active antiretroviral treatment. DESIGN: Observational cohort study. METHODS: Analysis of combined economic and clinical data of patients from the Johns Hopkins HIV Service, the provider of primary and sub-specialty care for a majority of HIV-infected patients in the Baltimore metropolitan region. All patients were enrolled in Medicaid and received care longitudinally in Maryland from 1 January 1995 through 31 December 1997. Monthly Medicaid payments were calculated for all inpatient and outpatient services by fiscal year, CD4 cell count, and use of protease inhibitors. RESULTS: For inpatients with a CD4 cell count < or = 50 x 10(6) cells/l, the total health care average monthly payments remained unchanged ($2629 in 1995, $2585 in 1997). Total mean monthly payments increased for those with a CD4 cell count > 50 x 10(6) cells/l (CD4 cell count 50-200 x 10(6) cells/l, $1172 in 1995 and $1615 in 1997, P < 0.05; CD4 cell count 201-500 x 10(6) cells/l, $1078 in 1995 and $1305 in 1997, P < 0.05). However, when data were stratified according to use of a protease inhibitor-containing regimen (used during approximately 50% of follow-up time in 1996-1997) it was found that hospital inpatient payments decreased significantly in all CD4 strata for patients on a protease inhibitor-containing regimen whereas pharmacy payments increased significantly. Inpatient payments associated with treating opportunistic illness were lower in 1996-1997 for patients receiving protease inhibitor therapy compared with those not receiving protease inhibitors. On balance, total health care payments tended to be slightly lower for patients receiving a protease inhibitor regimen. CONCLUSION: Although protease inhibitor-containing antiretroviral regimens are being used by only about half of our Medicaid-insured patients, when they are used, there are significantly lower hospital inpatient and community care costs, as well as lower costs associated with the treatment of opportunistic illness. Even with the concurrent increase in their pharmacy costs, total health care costs were stable or slightly lower for these patients. We believe this is a favorable result suggesting a good clinical value being achieved without an increase in costs.

Risk factors for pneumococcal disease in human immunodeficiency virus-infected patients.

To identify risk factors for pneumococcal infection among human immunodeficiency virus-infected patients, a nested case-control study was done in an urban university human immunodeficiency virus clinic. Subjects with pneumococcal illness seen between 1 January 1990 and 1 July 1994 (n=85) were randomly matched to controls from the same population. Patients with pneumococcal disease were more likely than controls to be African Americans (adjusted odds ratio [OR]=3.92), have <200 CD4 cells/mm3 (adjusted OR=3.38), have a history of any pneumonia (adjusted OR=3.28), and have an albumin level of <3.0 g/dL (adjusted OR=6.25). Use of zidovudine (adjusted OR=0.38) and pneumococcal vaccination when the subject had >200 CD4 cells/mm3 (adjusted OR=0.22) were less common in cases than in controls. Similar results were found when only cases with infections of usually sterile sites were analyzed. Pneumococcal vaccine may be most protective when it is administered before advanced immunodeficiency develops.

Anchor sequence-dependent endogenous processing of human immunodeficiency virus 1 envelope glycoprotein gp160 for CD4+ T cell recognition.

Human CD4+ T cell clones and cell lines were shown to lyse recombinant vaccinia virus-infected cells that synthesize the HIV-1 envelope glycoprotein gp160. The processing of endogenously synthesized gp160 for recognition by CD4+ T cells required that the protein, after synthesis on the rough endoplasmic reticulum and during subsequent cellular transport, remain attached to the luminal/extracellular membrane face by a hydrophobic anchor sequence.