To evaluate the relationship between regional body composition and liver disease (fibrosis or steatosis) in HIV/HCV co-infected individuals.
Whole body dual-energy X-ray absorptiometry (DXA) was performed in 173 HIV/HCV co-infected persons within 12 months of a liver biopsy. Significant fibrosis was defined as a METAVIR stage greater than 1. Steatosis was graded as: 0, none; 1, steatosis involving less than 5% of hepatocytes; 2, 5–29%; 3, 30–60%; 4 greater than 60%, and was defined as more than 0. Poisson regression with robust variance was used to estimate prevalence ratios of the outcome measures.
The population was 62% male and 84% black with a median body mass index of 25.2 kg/m2 (interquartile range 22.5, 29.3 kg/m2). No differences in regional body fat or fat distribution were observed in 42 patients with significant fibrosis compared to others with less fibrosis. However, the 77 individuals (45%) with steatosis had greater central fat than those without steatosis [prevalence ratio 1.04 per kg trunk fat; 95% confidence interval (CI) 1.04, 1.11], after adjusting for hepatic fibrosis (prevalence ratio 1.77; 95% CI 1.29, 2.42), uncontrolled HIV replication (viral load >400 copies/ml) (prevalence ratio 1.57; 95% CI 1.12, 2.22), age, sex, race and diabetes mellitus.
In HIV/HCV co-infected individuals, measures of regional body fat or fat distribution were not associated with hepatic fibrosis. In contrast, increased central adiposity by DXA, as well as concomitant fibrosis and uncontrolled HIV, were associated with hepatic steatosis. The extent to which weight loss and effective antiretroviral therapy can reduce the risk of steatosis deserves further investigation.
body composition; hepatic fibrosis; hepatitis C; HIV; steatosis
Data from 6 human immunodeficiency virus clinics showed improvements in clinic attendance after versus before a clinic-wide intervention (7% on short-term measure; 3% on longer-term measure). Several subgroups showed larger improvements: younger patients, new or reengaging patients, and patients with elevated viral loads.
Background. Retention in care for human immunodeficiency virus (HIV)–infected patients is a National HIV/AIDS Strategy priority. We hypothesized that retention could be improved with coordinated messages to encourage patients' clinic attendance. We report here the results of the first phase of the Centers for Disease Control and Prevention/Health Resources and Services Administration Retention in Care project.
Methods. Six HIV-specialty clinics participated in a cross-sectionally sampled pretest-posttest evaluation of brochures, posters, and messages that conveyed the importance of regular clinic attendance. 10 018 patients in 2008–2009 (preintervention period) and 11 039 patients in 2009–2010 (intervention period) were followed up for clinic attendance. Outcome variables were the percentage of patients who kept 2 consecutive primary care visits and the mean proportion of all primary care visits kept. Stratification variables were: new, reengaging, and active patients, HIV RNA viral load, CD4 cell count, age, sex, race or ethnicity, risk group, number of scheduled visits, and clinic site. Data were analyzed by multivariable log-binomial and linear models using generalized estimation equation methods.
Results. Clinic attendance for primary care was significantly higher in the intervention versus preintervention year. Overall relative improvement was 7.0% for keeping 2 consecutive visits and 3.0% for the mean proportion of all visits kept (P < .0001). Larger relative improvement for both outcomes was observed for new or reengaging patients, young patients and patients with elevated viral loads. Improved attendance among the new or reengaging patients was consistent across the 6 clinics, and less consistent across clinics for active patients.
Conclusion. Targeted messages on staying in care, which were delivered at minimal effort and cost, improved clinic attendance, especially for new or reengaging patients, young patients, and those with elevated viral loads.
To compare the early mortality pattern and causes of death among patients starting HAART in Brazil and the United States.
We analyzed the combined data from two clinical cohorts followed at the Johns Hopkins AIDS Service in Baltimore, United States, and the Evandro Chagas Clinical Research Institute AIDS Clinic in Rio de Janeiro, Brazil. Participants included those who entered either cohort between 1999 and 2007 and were antiretroviral naive. Follow-up was at 1 year since HAART initiation. Cox proportional hazards regression analysis was used to assess the role of the city on the risk of death.
A total of 859 and 915 participants from Baltimore and Rio de Janeiro, respectively, were included. In Rio de Janeiro, 64.7% of deaths occurred within 90 days of HAART initiation; in Baltimore, 48.9% occurred between 180 and 365 days. AIDS-defining illness (61.8%) and non-AIDS-defining illness (55.6%) predominated as causes of death in Rio de Janeiro and Baltimore, respectively. Risk of death was similar in both cities (hazard ratio 1.04; P value=0.95) after adjusting for CD4+ T cell count, age, sex, HIV risk group, prior AIDS-defining illness, and Pneumocystis jirovecii pneumonia and Mycobacterium avium prophylaxis. Individuals with CD4+ T cell count less than or equal to 50 cells/μl (hazard ratio 4.36; P = 0.001) or older (hazard ratio, 1.03; P = 0.03) were more likely to die.
Although late HIV diagnosis is a problem both in developed and developing countries, differences in the timing and causes of deaths clearly indicate that, besides interventions for early HIV diagnosis, different strategies to curb early mortality need to be tailored in each country.
antiretroviral therapy; causes of death; cohort; early mortality; HIV/AIDS
Fractures and cirrhosis are major causes of morbidity and mortality among HIV–HCV-coinfected individuals. It is not known whether vitamin D deficiency is associated with these outcomes.
Between 2005 and 2007, 116 HIV–HCV- coinfected individuals underwent dual-energy X-ray absorptiometry within 1 year of a liver biopsy. 25-Hydroxy-vitamin D (25OHD) and parathyroid hormone were measured from archived samples. Low bone mineral density (BMD) was defined as BMD≥2 standard deviations lower than age-, sex- and race-matched controls (Z-score ≤−2.0) at the total hip, femoral neck or lumbar spine. Histological fibrosis staging was assessed according to the METAVIR system (0 [no fibrosis] to 4 [cirrhosis]).
The cohort was 87% African-American and 63% male. The median age (IQR) was 49.9 years (46.5–53.3). A total of 89% had a CD4+ T-cell count >200 cells/mm3 and 64% were receiving HAART. The median 25OHD was 19 ng/ ml (IQR 11.0–26.0). Hypovitaminosis D (25OHD≤15 ng/ml) was present in 41% and secondary hyperparathyroidism, defined by parathyroid hormone >65 pg/ml, was present in 24%. In total, 27% had low BMD (Z-score ≤−2) at the spine, femoral neck or total hip, and 39% had significant hepatic fibrosis (METAVIR≥2). In multivariate analysis, vitamin D deficiency was not associated with significant fibrosis or with BMD at any site.
Vitamin D deficiency was highly prevalent in this mostly African-American HIV–HCV-coinfected population, but was not related to BMD or liver disease severity. These data suggest that efforts to increase vitamin D levels in this population may not improve bone or liver outcomes.
To determine whether tenofovir disoproxil fumarate (TDF) is associated with renal dysfunction when used as part of an initial antiretroviral regimen and to assess the effect of ritonavir-boosted protease inhibitor (PI/r) coadministration on renal function in TDF-treated patients.
Analysis from a prospective observational cohort.
We compared all antiretroviral-naive patients with an estimated glomerular filtration rate (eGFR) of more than 50 ml/min per 1.73 m2 (modification of diet in renal disease equation) who initiated either TDF (n = 201) or any alternative nucleoside reverse transcriptase inhibitor (NRTI) (n = 231) after 1 January 2002.
Patients taking both TDF and NRTIs experienced an initial decline in eGFR during the first 180 days of therapy, but eGFR stabilized between 180 and 720 days. There was no difference between TDF and NRTI use in 25 or 50% decline in eGFR at 1 or 2 years or in change in eGFR at 6, 12, or 24 months. Those taking TDF and a PI/r had a greater median decline in eGFR than those taking TDF and a non-NRTI at 6 months (P = 0.01), with trends at 12 (P = 0.08) and 24 months (P = 0.08). There was no difference in median GFR decline between those on an NRTI and PI/r vs. an NRTI and non-NRTI.
Our data are consistent with results of clinical trials, which have shown no evidence of renal toxicity when TDF is used as part of an initial regimen. Our results support the use of TDF as a component of the initial antiretroviral regimen, and suggest that the eGFR should be monitored more closely when TDF is used with a PI/r.
antiretroviral; kidney; nephrotoxicity; nucleoside analog reverse transcriptase inhibitor; protease inhibitor; renal; tenofovir
To examine the association between early HIV viremia and mortality after HIV-associated lymphoma.
Multicenter observational cohort study.
Center for AIDS Research Network of Integrated Clinical Systems cohort.
HIV-infected patients with lymphoma diagnosed between 1996 and 2011, who were alive 6 months after lymphoma diagnosis and with ≥2 HIV RNA values during the 6 months after lymphoma diagnosis.
Cumulative HIV viremia during the 6 months after lymphoma diagnosis, expressed as viremia copy-6-months.
Main outcome measure
All-cause mortality between 6 months and 5 years after lymphoma diagnosis.
Of 224 included patients, 183 (82%) had non-Hodgkin lymphoma (NHL) and 41 (18%) had Hodgkin lymphoma (HL). At lymphoma diagnosis, 105 (47%) patients were on antiretroviral therapy (ART), median CD4 count was 148 cells/µlL (IQR 54– 322), and 33% had suppressed HIV RNA (<400 copies/mL). In adjusted analyses, mortality was associated with older age [adjusted hazard ratio (AHR) 1.37 per decade increase, 95% CI 1.03–1.83], lymphoma occurrence on ART (AHR 1.63, 95% CI 1.02– 2.63), lower CD4 count (AHR 0.75 per 100 cell/µL increase, 95% CI 0.64–0.89), and higher early cumulative viremia (AHR 1.35 per log10copies × 6-months/mL, 95% CI 1.11–1.65). The detrimental effect of early cumulative viremia was consistent across patient groups defined by ART status, CD4 count, and histology.
Exposure to each additional 1-unit log10 in HIV RNA throughout the 6 months after lymphoma diagnosis, was associated with a 35% increase in subsequent mortality. These results suggest that early and effective ART during chemotherapy may improve survival.
AIDS; Burkitt lymphoma; diffuse large B-cell lymphoma; HIV; Hodgkin lymphoma; lymphoma; non-Hodgkin lymphoma
Prior research has documented sociodemographic disparities in the use of antiretroviral therapy (ART). Recent therapeutic developments and changing epidemiological profiles may have altered such disparities. We examine the extent to which socio-demographic differences in prescribed ART have changed between 2002 and 2008.
We analyzed data abstracted from medical records at 13 US sites participating in the Human Immunodeficiency Virus Research Network. Prescription of ART was assessed for each year in care for each patient. A total of 14,092 patients were followed up for 39,251 person-years. We examined ART use as a function of sex, race/ethnicity, human immunodeficiency virus risk group, age, and CD4 history (no test <500 cells/mm3, one or more tests between 500 and 350 cells/mm3, 1 test ≤350 cells/mm3, and 2 or more tests ≤350 cells/mm3). Using multiple logistic regression, we ascertained interactions between each of these variables and calendar year.
The overall percentage prescribed ART increased from 60% to 80% between 2002 and 2008. Among those with 2 or more CD4 tests ≤350 cells/mm3, the percentage increased from 82% to 92%. ART rates were higher for those with lower CD4 counts but increased over time for all CD4 groups and for all demographic groups. Nevertheless, sex and racial/ethnic disparities persisted. Significant interactions were obtained for CD4 history by year, age by year, and age by CD4 history.
Although prescription of ART became more widespread from 2002 to 2008, patients who were female, black, or younger still had lower ART rates than male, white, or older patients.
ART; disparities; time trends; utilization; sociodemographic differences
Studies have repeatedly found that providers miss 70-90% of opportunities to express empathy. Our study sought to characterize provider responses to patients’ emotions, with the overall goal of better understanding reasons for lack of empathic response.
We analyzed 47 visits between patients and their providers. We defined empathic opportunities as instances where patients expressed a strong negative emotion. We then developed thematic categories to describe provider response.
We found a total of 29 empathic opportunities within 21 visits. Provider responses were categorized as ignore, dismiss, elicit information, problem-solve, or empathize. An empathic statement occurred at some point in the response sequence in 13/29 opportunities (45%). When problem-solving was the initial response, empathic statements rarely occurred in subsequent dialogue. Among the 16 instances with no empathic statements, providers engaged in problem-solving in 8 (50%).
Similar to other studies, we found providers missed most opportunities to respond empathically to patient emotion. Yet contrary to common understanding, providers often addressed the problem underlying the emotion, especially when the problem involved logistical or biomedical issues, as opposed to grief.
With enhanced awareness, providers may better recognize situations where they can offer empathy in addition to problem-solving.
Antiretroviral therapy medication errors are common among hospitalized patients with human immunodeficiency virus (HIV) infection (29% of admissions on hospital day 1) but are quickly corrected (7% of admissions on hospital day 2). Compared with those admitted to the HIV/AIDS service, patients admitted to surgical services were at increased risk of errors.
Background. Antiretroviral therapy (ART) medication errors can lead to drug resistance, treatment failure, and death. Prior research suggests that ART medication errors are on the rise in US hospitals. This analysis provides a current estimate of inpatient antiretroviral prescribing errors.
Methods. Retrospective review of medication orders during the first 48 hours of hospitalization for patients with human immunodeficiency virus (HIV) infection admitted to the Johns Hopkins Hospital between 1 January and 31 December 2009. Errors were classified as (1) incomplete regimen, (2) incorrect dosage, (3) incorrect schedule, and (4) nonrecommended drug-drug combinations. Multivariable regression was used to identify factors associated with errors.
Results. A total of 702 admissions occurred in 2009. Of these, 380 had ART medications prescribed on the first day and 308 on the second day of hospitalization. A total of 145 ART medication errors in 110 admissions were identified on the first day (29%), and 22 errors were identified in 21 admissions on the second day (7%). The most common errors were incomplete regimen and incorrect dosage or schedule. Protease inhibitors accounted for the majority of dosing and scheduling errors (71%–73%). Compared with patients admitted to the HIV/AIDS service, those admitted to surgical services were at increased risk of errors (adjusted odds ratio, 3.10; 95% confidence interval, 1.18–8.18).
Conclusions. ART medication errors are common among hospitalized HIV-infected patients on the first day of admission, but most are corrected within 48 hours. Interventions are needed to safeguard patients and prevent serious complications of ART medication errors especially during the first 24 hours of hospitalization.
For optimal clinical benefit, HIV-infected patients should receive periodic outpatient care indefinitely. However, initially establishing HIV care and subsequent retention in care are problematic. This study examines establishment, retention, and loss to follow-up (LTFU) in a large, multi-site cohort over a 2-8 year period.
Medical record data were reviewed for 22,984 adult HIV patients receiving care at 12 clinics in the HIV Research Network between 2001-2009. Three dichotomous outcome measures were based on each patient's history of outpatient visits. Establishment reflects whether the patient made outpatient visits for longer than 6 months after initial enrollment. The retention measure reflects whether the patient had at least 2 outpatient visits separated by 90 days in each year in care. LTFU reflects whether the patient had no outpatient visits for more than 12 months without returning. Multiple logistic regression examined demographic and clinical correlates of each outcome, as well as the combined outcome of meeting all three measures.
Overall, 21.7% of patients never established HIV care after an initial visit. Among established patients, 57.4% did not meet the retention criterion in all years, and 34.9% were LTFU. Only 20.4% of all patients met all three criteria. The odds of successfully meeting all three criteria were higher for women, for older patients, for Hispanics compared with whites, and for those with CD4 levels ≤50 cells/mm3.
These data highlight the need to improve establishment and retention in HIV care.
HIV; Loss to follow-up; retention in care; outpatient use
Recent-infection testing assays/algorithms (RITAs) have been developed to exploit the titer and avidity of HIV antibody evolution following seroconversion for incidence estimation. The Vitros Anti-HIV 1+2 assay (Ortho-Clinical Diagnostics) was approved by the FDA to detect HIV-1 and HIV-2 infections. We developed a less-sensitive (LS) and an avidity-modified version of this assay to detect recent HIV infection. Seroconversion panels (80 subjects, 416 samples) were tested to calculate the mean duration of recent infection (MDR) for these assays. A panel from known long-term (2+ years) HIV-infected subjects on highly active antiretroviral therapy (HAART) (n = 134) and subjects with low CD4 counts (AIDS patients [n = 140]) was used to measure the false-recent rate (FRR) of the assays. Using a signal-to-cutoff ratio of 20 and the LS-Vitros assay gave a RITA MDR of 215 days (95% confidence interval [95% CI], ±65 days) and using an avidity index (AI) of 0.6 gave an MDR of 170 days (±44 days), while a combination of the two assays yielded a MDR of 146 days (±38.6) and an FRR of 8%. Misclassifying subjects with known long-term infection as recently infected occurred in 14% of AIDS patients and 29% (95% CI, 22, 38) of HAART subjects and 3% (95% CI, 0.8, 7.2) and 42% (95% CI, 33, 51), respectively, for the LS- and avidity-modified Vitros assays, with a misclassification rate of 15% (95% CI, 11, 20) overall using a dual-assay algorithm. Both modified Vitros assays can be used to estimate the length of time since seroconversion and in calculations for HIV incidence. Like other RITAs, they are subject to high FRR in subjects on HAART or with AIDS.
We showed a dramatic decrease in the human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) level in a community of patients who receive care in an urban region in the United States, suggesting a decreased risk of HIV transmission as treatment has improved in those under care.
(See the Editorial Commentary by Sax, on pages 605–608.)
Background. We have previously showed that as antiretroviral therapy has improved over time since 1995–1996, the likelihood of achieving virologic suppression has also improved. Antiretroviral therapy and antiretroviral therapy guidelines have continued to evolve, and we wished to determine the trend in human immunodeficiency virus (HIV-1) RNA levels over time in HIV-infected persons receiving care in our large urban HIV clinical practice in Baltimore, Maryland.
Methods. The HIV-1 RNA level was assessed each year from 1996 through 2010 at the date closest to 1 July for all patients in care and followed up in the Johns Hopkins HIV Clinical Cohort. The clinic population’s median HIV-1 RNA level and stratified threshold levels were plotted. The demographic characteristics of the population were also assessed over time.
Results. From 1996 (shortly after highly active antiretroviral therapy [HAART] was introduced) to 2010, the median HIV-1 RNA level decreased from 10 400 to <200 copies/mL. The proportion of patients with an HIV-1 RNA level >500 copies/mL decreased from 75% to only 16% during this same period. The population itself became older, had a higher proportion of women, and a lower proportion of patients with injection drug use as a transmission risk, but it was geographically stable. There was an increase in HAART use over time.
Discussion. Our results demonstrate the remarkable impact of increased use of and improved management with HAART in this urban HIV-infected population.
cost; HIV; utilization; CD4 count; HAART; HIV Research Network
Hospitalization rates for comorbid conditions among persons living with HIV in the current HAART era are unknown.
Hospitalization data from 2001 – 2008 were obtained on 11,645 adults receiving longitudinal HIV care at 4 geographically diverse U.S. HIV clinics within the HIV Research Network. Modified clinical classification software from the Agency for Healthcare Research and Quality assigned primary ICD-9 codes into diagnostic categories. Analysis was performed with repeated measures negative binomial regression.
During 2001 – 2008, the rate of AIDS defining illness (ADI) hospitalizations declined from 6.7 to 2.7 per 100 person years (PY), incidence rate ratio per year, 0.89 [0.87, 0.91]. Among the other diagnostic categories with average rates > 2 per 100 PY, cardiovascular hospitalizations increased over time (1.07 [1.03, 1.11]), while non-AIDS defining infection (0.98 [0.96, 1.00]), psychiatric (0.96 [0.93, 1.00]), and gastrointestinal/liver (0.96 [0.92, 1.00]) were slightly decreasing or stable. While less frequent overall, renal and pulmonary admissions also increased over time in univariate and multivariate analyses. Of all diagnostic categories, ADI admissions had the longest mean length of stay, 10.5 days.
ADI hospitalizations have continued to decline in recent years but are still relatively frequent and potentially costly given long lengths of stay. Increases or stability in the rates of chronic end-organ disease admissions imply a need for broader medical knowledge among individual clinicians and/or teams who care for persons living with HIV and a need for long-term access to medications for these conditions.
The Post-exposure Prophylaxis in Infants (PEPI)-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA) that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488); a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54). Antibody maturation and viral diversification were examined in these women.
Samples collected at enrollment (N = 2,561) and 12–24 months later (N = 1,306) were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM) diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples) and the known non-recent group (43 enrollment samples, 22 follow-up samples). Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US) with known recent infection (N = 102) and known non-recent infection (N = 67).
In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection.
Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection.
Viral suppression and viral breakthrough impact the humoral immune response to HIV infection. We evaluated the impact of viral suppression and viral breakthrough on results obtained with two cross-sectional HIV incidence assays.
All samples were collected from adults in the US who were HIV infected for >2 years. Samples were tested with the BED capture enzyme immunoassay (BED-CEIA) which measures the proportion of IgG that is HIV-specific, and with an antibody avidity assay based on the Genetic Systems 1/2+ O ELISA. We tested 281 samples: (1) 30 samples from 18 patients with natural control of HIV-1 infection known as elite controllers or suppressors (2) 72 samples from 18 adults on antiretroviral therapy (ART), with 1 sample before and 2–6 samples after ART initiation, and (3) 179 samples from 20 virally-suppressed adults who had evidence of viral breakthrough receiving ART (>400 copies/ml HIV RNA) and with subsequent viral suppression.
For elite suppressors, 10/18 had BED-CEIA values <0.8 normalized optical density units (OD-n) and these values did not change significantly over time. For patients receiving ART, 14/18 had BED-CEIA values that decreased over time, with a median decrease of 0.42 OD-n (range 0.10 to 0.63)/time point receiving ART. Three patterns of BED-CEIA values were observed during viral breakthrough: (1) values that increased then returned to pre-breakthrough values when viral suppression was re-established, (2) values that increased after viral breakthrough, and (3) values that did not change with viral breakthrough.
Viral suppression and viral breakthrough were associated with changes in BED-CEIA values, reflecting changes in the proportion of HIV-specific IgG. These changes can result in misclassification of patients with long-term HIV infection as recently infected using the BED-CEIA, thereby influencing a falsely high value for cross-sectional incidence estimates.
Geographic location may be related to the receipt of quality HIV healthcare services. Clinical outcomes and healthcare utilization were evaluated in rural, urban and peri-urban patients seen at high-volume U.S. urban-based HIV care sites.
Zip codes for 8,773 HIV patients followed in 2005 at 7 HIV Research Network sites were categorized as rural (population<10K), peri-urban (10K – 100K) and urban (>100K). Clinical and demographic characteristics, inpatient and outpatient (OP) utilization, AIDS defining illness rates, receipt of highly active antiretroviral therapy (HAART), opportunistic infection (OI) prophylaxis usage and virologic suppression were compared among patients, using Χ2 tests for categorical variables, t-tests for means, and logistic regression for HAART utilization.
HIV-infected rural (n=170) and peri-urban (n=215) patients were less likely to be Black or Hispanic than urban HIV patients. Peri-urban subjects were more likely to report MSM as their HIV risk factor than rural or urban subjects. Age, gender, CD4 or HIV-RNA distribution, virologic suppression, HAART usage or OI prophylaxis did not differ by geographic location. In multivariate analysis, rural and peri-urban patients were less likely to have ≥4 annual outpatient visits than urban patients. Rural patients were less likely to receive HAART if they were Black. Overall, geographic location (as defined by home zip code) did not affect receipt of HAART or OI prophylaxis.
Although demographic and healthcare utilization differences were seen among rural, peri-urban, and urban HIV patients, most HIV outcomes and medication use were comparable across geographic areas. As with HIV care for urban-dwelling patients, areas for improvement for non-urban HIV patients include access to HAART among minorities and IDUs.
rural; HIV/AIDS Care; HAART; Outcomes; Quality of care; highly active antiretroviral therapy; HIV Research Network
The epidemiology of human immunodeficiency virus (HIV) infection in the United States has changed significantly over the past 30 years. HIV/acquired immune deficiency syndrome (HIV/AIDS) is currently a disease of greater demographic diversity, affecting all ages, sexes, and races, and involving multiple transmission risk behaviors. At least 50,000 new HIV infections will continue to be added each year; however, one-fifth of persons with new infections may not know they are infected, and a substantial proportion of those who know they are infected are not engaged in HIV care. Barriers to early engagement in care may be specific to a demographic group. In this paper, the current epidemiology of HIV/AIDS in the United States is reviewed in order to understand the challenges, successes, and best practices for removing the barriers to effective diagnosis and receipt of HIV care within specific demographic groups.
To assess the effect of HIV-infection on postoperative survival among non-small cell lung cancer (NSCLC) patients.
A retrospective cohort study compared 22 HIV-infected lung cancer patients to 2,430 lung cancer patients with HIV-unspecified status resected at Johns Hopkins Hospital from 1985-2009. Sub-cohort comparative analyses were performed using individual matching methods.
Thirty day mortality rates did not differ between HIV-infected and HIV-unspecified patients. Survival rates in HIV-infected lung cancer patients were significantly shorter than in HIV-unspecified patients (median 26 vs. 48 months; p=0.001). After adjustment, the relative hazard of mortality among HIV-infected NSCLC patients was ≥3 fold that of HIV- unspecified patients (aHR=3.08, 95% CI 1.85; 5.13). When additional surgical characteristics were modeled in a matched sub-cohort, the association remained statistically significant (aHR=2.31, 95% CI 1.11; 4.81). Moreover, HIV-infected lung cancer patients with CD4 counts <200 cells/mm3 had shortened median survival than those with CD4 ≥200 cells/mm3 (8 vs. 40 months; p=0.031). Postoperative pulmonary and infectious complications were also elevated in the HIV-infected group (p=0.001 and <0.001, respectively). After surgery, median time to cancer progression was shorter among HIV-infected patients (20.4 months) versus HIV-unspecified patients (p=0.061).
HIV-infected NSCLC patients are associated with more postoperative complications, rapid progression to disease recurrence and poorer postoperative survival. Optimizing immune status prior to surgery and careful patient selection based on DLCO may improve patient outcomes.
Lung Cancer Surgery; Infection; Outcomes
Insulin and its plasma membrane receptor constitute an ancient response system critical to cell growth and differentiation. Studies using intact Rana pipiens oocytes have shown that insulin can act at receptors on the oocyte surface to initiate resumption of the first meiotic division. We have reexamined the insulin-induced cascade of electrical and ion transport-related plasma membrane events using both oocytes and intact plasma membranes in order to characterize the insulin receptor-steroid response system associated with the meiotic divisions.
[125I]Insulin binding (Kd = 54 ± 6 nM) at the oocyte plasma membrane activates membrane serine protease(s), followed by the loss of low affinity ouabain binding sites, with a concomitant 3–4 fold increase in high affinity ouabain binding sites. The changes in protease activity and ouabain binding are associated with increased Na+/Ca2+ exchange, increased endocytosis, decreased Na+ conductance resulting in membrane hyperpolarization, increased 2-deoxy-D-glucose uptake and a sustained elevation of intracellular pH (pHi). Hyperpolarization is largely due to Na+-channel inactivation and is the main driving force for glucose uptake by the oocyte via Na+/glucose cotransport. The Na+ sym- and antiporter systems are driven by the Na+ free energy gradient generated by Na+/K+-ATPase. Shifts in α and/or β Na+-pump subunits to caveolar (lipid raft) membrane regions may activate Na/K-ATPase and contribute to the Na+ free energy gradient and the increase in both Na+/glucose co-transport and pHi.
Under physiological conditions, resumption of meiosis results from the concerted action of insulin and progesterone at the cell membrane. Insulin inactivates Na+ channels and mobilizes fully functional Na+-pumps, generating a Na+ free energy gradient which serves as the energy source for several membrane anti- and symporter systems.
Insulin; Progesterone; Meiosis; Oocyte; Ouabain; Na/K-ATPase; Protease
The U.S. National HIV/AIDS Strategy targets for 2015 include increasing access to care and improving health outcomes for persons living with HIV in the United States (PLWH-US).
To demonstrate the utility of the NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) for monitoring trends in the HIV epidemic in the United States and to present trends in HIV treatment and related health outcomes.
Trends from annual cross-sectional analyses comparing patients from pooled, multicenter, prospective, clinical HIV cohort studies with PLWH-US, as reported to national surveillance systems in 40 states.
U.S. HIV outpatient clinics.
HIV-infected adults with 1 or more HIV RNA plasma viral load (HIV VL) or CD4 T-lymphocyte (CD4) cell count measured in any calendar year from 1 January 2000 to 31 December 2008.
Annual rates of antiretroviral therapy use, HIV VL, and CD4 cell count at death.
45 529 HIV-infected persons received care in an NA-ACCORD–participating U.S. clinical cohort from 2000 to 2008. In 2008, the 26 030 NA-ACCORD participants in care and the 655 966 PLWH-US had qualitatively similar demographic characteristics. From 2000 to 2008, the proportion of participants prescribed highly active antiretroviral therapy increased by 9 percentage points to 83% (P < 0.001), whereas the proportion with suppressed HIV VL (≤2.7 log10 copies/mL) increased by 26 percentage points to 72% (P < 0.001). Median CD4 cell count at death more than tripled to 0.209 × 109 cells/L (P < 0.001).
The usual limitations of observational data apply.
The NA-ACCORD is the largest cohort of HIV-infected adults in clinical care in the United States that is demographically similar to PLWH-US in 2008. From 2000 to 2008, increases were observed in the percentage of prescribed HAART, the percentage who achieved a suppressed HIV VL, and the median CD4 cell count at death.
Primary Funding Source
National Institutes of Health, Centers for Disease Control and Prevention, Canadian Institutes of Health Research, Canadian HIV Trials Network, and the government of British Columbia, Canada.
To examine long-term effects of antiretroviral therapy (ART) on kidney function, we evaluated the incidence and risk factors for chronic kidney disease (CKD) among ART-naive, HIV-infected adults and compared changes in estimated glomerular filtration rates (eGFR) before and after starting ART.
Multicenter observational cohort study of patients with at least one serum creatinine measurement before and after initiating ART. Cox proportional hazard models, and marginal structure models examined CKD risk factors; mixed-effects linear models examined eGFR slopes.
Three thousand, three hundred and twenty-nine patients met entry criteria, contributing 10 099 person-years of observation on ART. ART was associated with a significantly slower rate of eGFR decline (from −2.18 to −1.37 ml/min per 1.73 m2 per year; P = 0.02). The incidence of CKD defined by eGFR thresholds of 60, 45 and 30 ml/min per 1.73 m2 was 10.5, 3.4 and 1.6 per 1000 person-years, respectively. In adjusted analyses black race, hepatitis C coinfection, lower time-varying CD4 cell count and higher time-varying viral load on ART were associated with higher CKD risk, and the magnitude of these risks increased with more severe CKD. Tenofovir and a ritonavir-boosted protease inhibitor (rPI) was also associated with higher CKD risk [hazard odds ratio for an eGFR threshold <60 ml/min per 1.73 m2: 3.35 (95% confidence interval (CI) = 1.40–8.02)], which developed in 5.7% of patients after 4 years of exposure to this regimen-type.
ART was associated with reduced CKD risk in association with CD4 cell restoration and plasma viral load suppression, despite an increased CKD risk that was associated with initial regimens that included tenofovir and rPI.
antiretroviral therapy; chronic kidney disease; tenofovir
With improved combination antiretroviral therapy (ART)-related survival, diabetes and hypertension increasingly contribute to morbidity and mortality among individuals with HIV. However, there is limited data on diabetes and blood pressure control in this population. We examined whether virologic control is associated with control of diabetes and hypertension.
We examined HIV viral load, hemoglobin A1c (HbA1c), and blood pressure measurements from 70 diabetics and 291 hypertensives in the Johns Hopkins HIV Clinical Cohort, an urban, university-based cohort. All patients were treated for HIV and diabetes or hypertension. HbA1c and HIV-1 RNA were captured electronically from laboratory data, and blood pressure was collected electronically from vital signs taken at clinic visits. We used HIV-1 RNA values within 30 days of the HbA1c measurement or blood pressure measurement. The relationships between HIV-1 RNA and HbA1c and HIV-1 RNA and blood pressure were examined using separate random effects generalized least squares linear regression models.
The study sample was predominantly male and black, with a high prevalence of comorbid hepatitis C virus infection and psychiatric illness. In multivariable analysis, each log10 increase in HIV-1 RNA was associated with higher HbA1c (β=0.47 units, p<0.001) among diabetics and higher mean arterial pressure (MAP) among hypertensive patients (β=1.95 mmHg, p<0.001).
Suboptimal control of HIV, indicated by detectable viral load, correlates with suboptimal control of diabetes and hypertension, indicated by higher HbA1c and MAP. Achieving control of multiple medical comorbidities and HIV simultaneously may require expansion of current adherence interventions focused primarily on antiretroviral therapy.
HIV; Diabetes; Hypertension