Risk of End-Stage Renal Disease in HIV-Positive Potential Live Kidney Donors.

New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load <400 copies/mL, and CD4+ count ≥500 cells/µL, the 9-year cumulative incidence of ESRD was higher than that of their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive individuals with no comorbidities and well-controlled disease may be considered low-risk kidney donor candidates.

Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: HIV infection has been associated with an increased risk of chronic kidney disease (CKD). Little is known about the prevalence of CKD in individuals with high CD4 cell counts prior to initiation of antiretroviral therapy (ART). We sought to address this knowledge gap. METHODS: We describe the prevalence of CKD among 4637 ART-naïve adults (mean age 36.8 years) with CD4 cell counts > 500 cells/µL at enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. CKD was defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and/or dipstick urine protein ≥ 1+. Logistic regression was used to identify baseline characteristics associated with CKD. RESULTS: Among 286 [6.2%; 95% confidence interval (CI) 5.5%, 6.9%] participants with CKD, the majority had isolated proteinuria. A total of 268 participants had urine protein ≥ 1+, including 41 with urine protein ≥ 2+. Only 22 participants (0.5%) had an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) , including four who also had proteinuria. Baseline characteristics independently associated with CKD included diabetes [adjusted odds ratio (aOR) 1.73; 95% CI 1.05, 2.85], hypertension (aOR 1.82; 95% CI 1.38, 2.38), and race/ethnicity (aOR 0.59; 95% CI 0.37, 0.93 for Hispanic vs. white). CONCLUSIONS: We observed a low prevalence of CKD associated with traditional CKD risk factors among ART-naïve clinical trial participants with CD4 cell counts > 500 cells/µL.

Glomerular filtration rate estimated using creatinine, cystatin C or both markers and the risk of clinical events in HIV-infected individuals.

OBJECTIVES: The accuracy and precision of glomerular filtration rate (GFR) estimating equations based on plasma creatinine (GFR(cr)), cystatin C (GFR(cys)) and the combination of these markers (GFR(cr-cys)) have recently been assessed in HIV-infected individuals. We assessed the associations of GFR, estimated by these three equations, with clinical events in HIV-infected individuals. METHODS: We compared the associations of baseline GFR(cr), GFR(cys) and GFR(cr-cys) [using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations] with mortality, cardiovascular events (CVEs) and opportunistic diseases (ODs) in the Strategies for the Management of Antiretroviral Therapy (SMART) study. We used Cox proportional hazards models to estimate unadjusted and adjusted hazard ratios per standard deviation (SD) change in GFR. RESULTS: A total of 4614 subjects from the SMART trial with available baseline creatinine and cystatin C data were included in this analysis. Of these, 99 died, 111 had a CVE and 121 had an OD. GFR(cys) was weakly to moderately correlated with HIV RNA, CD4 cell count, high-sensitivity C-reactive protein, interleukin-6, and D-dimer, while GFR(cr) had little or no correlation with these factors. GFR(cys) had the strongest associations with the three clinical outcomes, followed closely by GFR(cr-cys), with GFR(cr) having the weakest associations with clinical outcomes. In a model adjusting for demographics, cardiovascular risk factors, HIV-related factors and inflammation markers, a 1-SD lower GFR(cys) was associated with a 55% [95% confidence interval (CI) 27-90%] increased risk of mortality, a 21% (95% CI 0-47%) increased risk of CVE, and a 22% (95% CI 0-48%) increased risk of OD. CONCLUSIONS: Of the three CKD-EPI GFR equations, GFR(cys) had the strongest associations with mortality, CVE and OD.

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.

Comparison of initial combination antiretroviral therapy with a single protease inhibitor, ritonavir and saquinavir, or efavirenz.

OBJECTIVE: To compare the effectiveness of initial highly active antiretroviral therapy with either: a single protease inhibitor (PI); ritonavir (RTV)/saquinavir (SQV); or efavirenz (EFV) plus nucleoside reverse transcriptase inhibitors. DESIGN: Cohort study. SETTING: Urban HIV clinic. PATIENTS: Five-hundred and forty-five HIV-1-infected individuals with minimal antiretroviral exposure who started combination therapy with > or = 3 antiretroviral drugs and > or = 1 NRTI to which they had not previously been exposed (single PI, 416; RTV/SQV, 68; EFV, 61). MAIN OUTCOME MEASURES: HIV-1 RNA < 400 copies/ml within 8 months of starting therapy; time to HIV-1 RNA rebound to > 1000 copies/ml in the subset of patients achieving initial viral suppression; change in CD4 cell count from baseline within 12 months of starting therapy. RESULTS: By intent-to-treat analysis, initial viral suppression was achieved by 72% of patients in the EFV group, compared to 49% in the single PI group (P = 0.001) and 51% in the RTV/SQV group (P = 0.019). Among patients who achieved initial viral suppression, time to viral rebound was similar in the three groups. Durable viral suppression (> or = 3 consecutive HIV-1 RNA levels < 400 copies/ml for > 6 months) was achieved by 53% of patients in the EFV group, 26% in the single PI group, and 29% in the RTV/SQV group (P < 0.05 for both comparisons with EFV). The median CD4 cell count increase was 139 x 10(6) cells/l, and was similar in the three groups. CONCLUSIONS: In agreement with a recent clinical trial, use of initial EFV-based combination antiretroviral therapy was associated with higher rates of viral suppression than PI-based therapy in a clinical cohort.

Detrimental effects of continued illicit drug use on the treatment of HIV-1 infection.

OBJECTIVE: To identify the effects of substance abuse status (active, former, and never) on utilization of highly active antiretroviral therapy (HAART), medication adherence, and virologic and immunologic responses to therapy. DESIGN: Prospective cohort study of 764 HIV-1-infected patients who attended an urban HIV clinic and participated in a standardized interview. MAIN OUTCOME MEASURES: Past utilization of HAART, self-reported nonadherence with antiretroviral therapy, and changes in HIV-1 RNA level and CD4+ lymphocyte count relative to prior peak and nadir, respectively. RESULTS: Forty-four percent of active drug users failed to utilize HAART compared with 22% of former drug users and 18% of non-drug users (p <.001 for both comparisons). Among participants who were taking antiretroviral therapy when interviewed, active drug users were more likely to report medication nonadherence (34% vs. 24% of nonusers and 17% of former users), had a smaller median reduction in HIV-1 RNA from baseline (0.8 log10 copies/ml vs. 1.7 in nonusers and 1.6 in former users), and had smaller median increases in CD4+ lymphocyte count from baseline (65 cells/mm3 vs. 116 in nonusers and 122 in former users) (p <.05 for all comparisons with active users). CONCLUSIONS: Active drug use was strongly associated with underutilization of HAART, nonadherence, and inferior virologic and immunologic responses to therapy, whereas former drug users and non-drug users were similar in all outcomes. Effective strategies are needed that integrate HIV-1 and substance abuse treatments.

Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions.

BACKGROUND: In clinical trials, highly active antiretroviral therapy (HAART) reduces plasma HIV-1 RNA levels to less than 500 copies/mL in 60% to 90% of patients with HIV-1 infection. The performance of such therapy outside of the clinical trial setting is unclear. OBJECTIVE: To determine factors associated with failure to suppress HIV-1 RNA levels and adverse drug reactions in a cohort of patients in whom protease inhibitor-containing therapy was begun in a large urban clinic. DESIGN: Retrospective cohort study. SETTING: Johns Hopkins HIV Clinic in Baltimore, Maryland. PATIENTS: 273 protease inhibitor-naive patients began taking a protease inhibitor regimen containing at least one other antiretroviral drug to which the patients had not previously been exposed. MEASUREMENTS: Demographic variables, plasma HIV-1 RNA levels, CD4+ lymphocyte counts, and adverse drug reactions. RESULTS: Levels of HIV-1 RNA were undetectable in 42% of the cohort at 1 to 90 days, in 44% at 3 to 7 months, and in 37% at 7 to 14 months. Factors associated with failure to suppress viral load at two or more time points included higher rates of missed clinic appointments, nonwhite ethnicity, age 40 years or younger, injection drug use, lower baseline CD4+ lymphocyte count, and higher baseline viral load. In a multivariate model, only higher rates of missed clinic appointments were independently associated with viral suppression at 1 year. Ritonavir was associated with adverse drug reactions about twice as frequently as indinavir or nelfinavir, and women experienced significantly more adverse effects than men. CONCLUSIONS: Unselected patients in whom HAART is started in a clinic setting achieve viral suppression substantially less frequently than do patients in controlled clinical trials. Missed clinic visits were the most important risk factor for failure to suppress HIV-1 RNA levels. Studies are needed to identify interventions that maximize the performance of HAART in inner-city clinics.

Mending a broken HAART: a report from the 2nd International Workshop on Salvage Therapy.

AIDS: Data from a study at the Johns Hopkins HIV clinic shows that 63 percent of patients taking their first combination regimen containing a protease inhibitor (PI) fail to suppress their HIV levels below 500 c/ml at the one year mark in treatment. The subject of the 2nd International Workshop on Salvage Therapy was how to best treat these patients afterwards. One researcher described salvage therapy as "mayhem." He noted that among 114 patients studied at the University of Alabama, there were 242 unique antiretroviral regimens prescribed, and each patient had an average of 9.4 regimen events or drug holidays. Only three patients shared an identical sequence of events. Other topics under discussion at the workshop included the role of drug holidays, monthly cyclic therapy, Mega-HAART, and the optimal sequencing of NRTIs and PIs.^ieng

Vancomycin-resistant and vancomycin-susceptible enterococcal bacteremia: comparison of clinical features and outcomes.

Vancomycin-resistant Enterococcus (VRE) is a major nosocomial pathogen. We collected clinical and laboratory data on 93 hospitalized adults with VRE bacteremia and 101 adults with vancomycin-susceptible enterococcal (VSE) bacteremia. Risk factors for VRE bacteremia included central venous catheterization, hyperalimentation, and prolonged hospitalization prior to the initial blood culture. VRE-infected patients were less likely to have undergone recent surgery or have polymicrobial bacteremia, suggesting a pathogenesis distinct from traditional VSE bacteremia. Prior exposure to metronidazole was the only significant pharmacologic risk factor for VRE bacteremia. Animal studies suggest metronidazole potentiates enterococcal overgrowth in the gastrointestinal tract and translocation into the bloodstream. An increasing APACHE II score was the major risk factor for death in a multivariate analysis, with VRE status being of only borderline significance.

Hand care begins with prevention in elementary schools.

OBJECTIVES: The purpose of this paper is to provide background information on the epidemic proportions of hand injuries related to computer use. It offers a solution of early health education in prevention of cumulative trauma disorders (CTDs) through specially designed instruction in elementary schools. STUDY DESIGN: The current literature is reviewed. Some physical impairments caused by poor biomechanics and computer overuse are identified. Disability factors are highlighted in relation to how the physical impairment affects an individual's performance in the domain of work. Handicapping factors that are the result of the individual's decline in performance roles of worker are noted. These factors impact our society in dollars spent on medical insurance and worker's compensation claims. A review of a pilot project aimed at early education in hand health basics is introduced, as a proactive ergonomic solution to the present epidemic of cumulative trauma disorders. RESULTS: A positive response was displayed by the 950 elementary students and their staff to a 20-min program that introduced concepts of posture at the keyboard and basic upper body stretches. Children were instructed in their individual classes during their computer lab time. Daily follow-up, particularly for the forearm and hand stretches, was fostered by the computer lab coordinator, teachers, and wall posters. Parents were informed through a summary article printed in the monthly school newsletter. CONCLUSIONS: Wellness thinking and living can be learned at an early age to assure that basic principles of work practice such as posture and upper body stretches become a life skill. Review of the literature supports programs to educate individuals at an early age to develop life skills that would minimize the occurrence of cumulative trauma disorders, especially in relation to the use of computers.