Evaluation of disparity in care for perforated appendicitis in a universal healthcare system.

PURPOSE: Racial and socioeconomic disparities have been reported in the management of appendicitis. Perforated appendicitis (PA) is used as an index for barriers to care due to delays in treatment. This study evaluates the effect of racial and socioeconomic differences on the likelihood of PA in a universally insured national healthcare system. METHODS: A retrospective review of pediatric patients enrolled in TRICARE who underwent appendectomy during a 5-year period was performed. Logistic regression was used to examine the association between ethnicity, age, gender, parent, or guardian marital status and deployment status of the active duty parent, type of facility, and type of admission with the odds of perforated appendicitis. RESULTS: A total of 3124 children met inclusion criteria. One-third of children carried the diagnosis of PA. Increased odds of PA was associated with younger age of patient among children of military personnel with enlisted ranks and senior officer ranks. CONCLUSION: In a universal healthcare system, no disparities across race with regard to presentation of appendicitis were identified. Increased odds of perforated appendicitis were observed in younger patients, but this was demonstrated in families of both high and low socioeconomic status. Universal coverage does appear to eliminate some barriers to healthcare.

Chronic kidney disease at presentation is not an independent risk factor for AIDS-defining events or death in HIV-infected persons.

Studies have documented an association between chronic kidney disease (CKD) and increased risk of end stage renal disease, death and comorbidities, including cardiovascular disease and metabolic syndrome, in the general population. However, there is little data on the relationship between CKD and ADE (AIDS defining event), and to our knowledge, no studies have analyzed death as a competing risk for ADE among HIV-infected persons. An observational cohort study was performed to determine the incidence and risks for developing an ADE or death among HIV-infected persons with and without CKD from 1998 - 2005. CKD was defined as an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 using the CKDEpidemiology Collaboration (CKD-EPI) equation. Log rank test and Cox regression which determined time to development of ADE and/or death as combined and separate outcomes, and competing risk models for ADE versus mortality, were performed. Among the 2,127 persons that contributed to the 5,824 person years of follow-up: 22% were female, 34% African American, 38% on HAART, and 3% had CKD at baseline. ADE occurred in 227 (11%) persons and there were 80 (4%) deaths. CKD was not significantly associated with ADE/death (HR 1.3, 95% CIs: 0.5, 3.2), ADE (HR 1.0, 95% CIs: 0.4, 3.1), or death (HR 1.6, 95% CIs: 0.4, 3.1). Competing risk analyses confirmed no statistically significant associations between CKD and these outcomes. CKD was uncommon in HIV-infected persons presenting for care in this racially diverse cohort, and was not independently associated with risk of developing an ADE or dying during follow-up.

Hemoglobin may contribute to sex differences in mortality among HIV-infected persons in care.

BACKGROUND: Some retrospective studies have found that HIV-infected women have a higher mortality risk than men after adjusting for baseline characteristics, while others have not. Anemia is a known predictor of HIV-related mortality. We assessed whether anemia contributed to the sex difference in mortality in our cohort. METHODS: We conducted a retrospective cohort study among HIV-infected persons in care at the Comprehensive Care Center (Nashville, TN) between 1998 and 2009. Cox proportional hazards models compared time from first clinic visit to death and AIDS-defining events (ADE), adjusted for baseline characteristics with and without baseline hemoglobin. RESULTS: Of 3,633 persons, 879 (24%) were women. Women had lower median baseline hemoglobin compared to men: 12.4 g/dL (inter-quartile range (IQR) 11.3-13.4) vs. 14.4 (IQR 13.1-15.5), respectively (P<0.001). In multivariable models without hemoglobin, the risk of death was higher among women: hazard ratio (HR) 1.46 (95% confidence interval (CI) 1.17, 1.82; P=0.001). In multivariable models with hemoglobin, the risk of death in women was diminished and no longer statistically significant: HR 1.2 (95% CI 0.93, 1.55; P=0.17). The risk of ADE was higher among women in both models, but not statistically significant: HR 1.1 (95% CI 0.85-1.42; P=0.46) in the model without hemoglobin and 1.11 (95% CI 0.82-1.48; P=0.50) in the model with hemoglobin. Hemoglobin was a strong predictor of death: HR 0.88 per 1 g/dL increase (95% CI 0.83, 0.93; P<0.001). CONCLUSION: In our study population of HIV-infected persons in care, women had lower baseline hemoglobin, and lower hemoglobin contributed to their higher risk of ADE and death.

Virologic, immunologic and clinical responses in foreign-born versus US-born HIV-1 infected adults initiating antiretroviral therapy: an observational cohort study.

INTRODUCTION: Mortality rates within the first year of combination antiretroviral therapy (cART) initiation are several-fold higher in resource-limited countries than in resource-replete settings. However studies in western countries examining virologic, immunologic and clinical responses after cART initiation in indigenous versus non-indigenous populations have shown mixed results. This study aimed to determine whether there is a difference in these outcomes in a United States setting between foreign-born and US-born patients. METHODS: This retrospective observational cohort study of HIV-1 infected adults in one urban clinic in the United States compared virologic suppression, immune recovery and rates of AIDS defining events (ADEs) within the first year of cART using linear mixed effect models, log rank tests and Cox proportional hazard models. Data were analyzed for 94 foreign-born and 1242 US-born patients. RESULTS: Foreign-born patients were younger (31.7 years versus 38.5 years), more often female (38.3% versus 27.1%), less often injection drug users (3.2% versus 9.5%) or men who have sex with men (19.0% versus 54.5%), and had higher loss to follow-up rates (14.9% versus 6.2%). No significant differences were detected between the groups in suppression of plasma HIV-1 RNA, CD4+ cell recovery or development of ADEs. CONCLUSIONS: During the first year on cART, virologic suppression, immune recovery and development of ADEs were comparable between foreign-born and US-born patients in care in a US clinic. Differential rates of loss to follow-up warrant further investigation in the foreign-born population.

An optimal body mass index range associated with improved immune reconstitution among HIV-infected adults initiating antiretroviral therapy.

BACKGROUND: Higher body mass index (BMI) was associated with slower human immunodeficiency virus (HIV) disease progression before the availability of effective antiretroviral therapy (ART), but the relationship between pretreatment BMI and CD4(+) lymphocyte recovery on ART is not well described. METHODS: We conducted an observational cohort study of HIV-infected, ART-naive adults starting treatment at a clinic affiliated with Vanderbilt University in Nashville, Tennessee. We assessed the relationship between pretreatment BMI and CD4(+) lymphocyte count change from baseline to 12 months in all subjects, among those with plasma HIV-1 RNA levels <400 copies/mL for ≥ 6 months and those with <10% change in weight during follow-up. Linear regression models were adjusted for age, sex, race, protease inhibitor usage, year of ART initiation, and baseline CD4(+) lymphocyte count and HIV-1 RNA level. RESULTS: A total of 915 patients met inclusion criteria; 78% were male, and their median age, BMI, and CD4(+) lymphocyte count were 39 years, 24 kg/m², and 171 cells/µL, respectively. The CD4(+) lymphocyte increase at 12 months was greatest among patients with a pretreatment BMI of ~25-30 kg/m² and diminished above and below this range (P = .03). Similar patterns were observed in the subgroup analyses. Among patients with a pretreatment CD4(+) lymphocyte count < 200 cells/µL, a BMI of ~25 kg/m² was associated with the highest odds of reaching a CD4(+) lymphocyte count > 350 cells/µL at 12 months (P = .05). CONCLUSIONS: 12-month immune reconstitution on ART was highest among patients commonly classified as overweight, suggesting there may be an optimal BMI range for immune recovery on ART.

Drug use and receipt of highly active antiretroviral therapy among HIV-infected persons in two U.S. clinic cohorts.

OBJECTIVE: Drug use and receipt of highly active antiretroviral therapy (HAART) were assessed in HIV-infected persons from the Comprehensive Care Center (CCC; Nashville, TN) and Johns Hopkins University HIV Clinic (JHU; Baltimore, MD) between 1999 and 2005. METHODS: Participants with and without injection drug use (IDU) history in the CCC and JHU cohorts were evaluated. Additional analysis of persons with history of IDU, non-injection drug use (NIDU), and no drug use from CCC were performed. Activity of IDU and NIDU also was assessed for the CCC cohort. HAART use and time on HAART were analyzed according to drug use category and site of care. RESULTS: 1745 persons were included from CCC: 268 (15%) with IDU history and 796 (46%) with NIDU history. 1977 persons were included from JHU: 731 (35%) with IDU history. Overall, the cohorts differed in IDU risk factor rates, age, race, sex, and time in follow-up. In multivariate analyses, IDU was associated with decreased HAART receipt overall (OR = 0.61, 95% CI: [0.45-0.84] and OR = 0.58, 95% CI: [0.46-0.73], respectively for CCC and JHU) and less time on HAART at JHU (0.70, [0.55-0.88]), but not statistically associated with time on HAART at CCC (0.78, [0.56-1.09]). NIDU was independently associated with decreased HAART receipt (0.62, [0.47-0.81]) and less time on HAART (0.66, [0.52-0.85]) at CCC. These associations were not altered significantly whether patients at CCC were categorized according to historical drug use or drug use during the study period. CONCLUSIONS: Persons with IDU history from both clinic populations were less likely to receive HAART and tended to have less cumulative time on HAART. Effects of NIDU were similar to IDU at CCC. NIDU without IDU is an important contributor to HAART utilization.

Non-AIDS-defining events among HIV-1-infected adults receiving combination antiretroviral therapy in resource-replete versus resource-limited urban setting.

OBJECTIVE: To compare incidence and distribution of non-AIDS-defining events (NADEs) among HIV-1-infected adults receiving combination antiretroviral therapy (cART) in urban sub-Saharan African versus United States settings. DESIGN: Retrospective cohort analysis of clinical trial and observational data. METHODS: Compared crude and standardized (to US cohort by age and sex) NADE rates from two urban adult HIV-infected cART-initiating populations: a clinical trial cohort in Gaborone, Botswana (Botswana) and an observational cohort in Nashville, Tennessee (USA). RESULTS: Crude NADE incidence rates were similar: 10.0 [95% confidence interval 6.3-15.9] per 1000 person-years in Botswana versus 12.4 [8.4-18.4] per 1000 person-years in the United States. However, after standardizing to an older, predominantly male US population, the overall NADE incidence rates were higher in Botswana [18.7 (8.3-33.1) per 1000 person-years]. Standardized rates differed most for cardiovascular events (8.4 versus 5.0 per 1000 person-years) and non-AIDS-defining malignancies (8.0 versus 0.5 per 1000 person-years) - both higher in Botswana. Conversely, hepatic NADE rates were higher in the United States (4.0 versus 0.0 per 1000 person-years), whereas renal NADE rates [3.0 per 1000 person-years (United States) versus 2.4 per 1000 person-years (Botswana)] were comparable. CONCLUSION: Crude NADE incidence rates were similar between cART-treated patients in a US observational cohort and a sub-Saharan African clinical trial. However, when standardized to the US cohort, overall NADE rates were higher in Botswana. NADEs appear to be a significant problem in our sub-Saharan African setting, and the monitoring, prevention, and treatment of NADEs should be a critical component of care in resource-limited settings.

Tuberculosis risk before and after highly active antiretroviral therapy initiation: does HAART increase the short-term TB risk in a low incidence TB setting?

OBJECTIVE: To evaluate the short-term and long-term effects of highly active antiretroviral therapy (HAART) on tuberculosis (TB) risk compared with risk without HAART in a low TB incidence setting. DESIGN: An observational cohort study among HIV-infected persons in care at the Comprehensive Care Center (Nashville, TN) between January 1998 and December 2008. METHODS: A marginal structural model was used to estimate the effect of HAART on short-term (≤180 days) and long-term (>180 days) TB risk, with CD4⁺ lymphocyte count incorporated as a time-updated covariate. RESULTS: Of 4534 HIV-infected patients, 34 developed TB (165 per 100,000 person-years; 20,581 person-years of follow-up). Seventeen cases occurred among persons not on HAART or >30 days after HAART discontinuation (212 per 100,000 person-years; 8019 person-years of follow-up). Seventeen occurred among persons on HAART (135 per 100,000 person-years; 12,562 person-years of follow-up); 10 in the first 180 days (402 per 100,000 person-years; 2489 person-years of follow-up); and 7 after more than 180 days (69 per 100,000 person-years; 10,073 person-years of follow-up). After adjusting for the most recent CD4⁺ lymphocyte count, the risk of TB in the first 180 days of HAART exposure relative to no HAART was 0.68 (0.14-3.22, P = 0.63). CONCLUSIONS: In this low TB incidence setting, the TB rate in the first 180 days of HAART was almost twice as high as persons not on HAART. However, after adjusting for most recent CD4⁺ count, there was no significant difference in TB risk between these 2 groups. This suggests that low recent CD4⁺ lymphocyte count influences TB risk during the first 180 days of HAART.

The relationship between injection and noninjection drug use and HIV disease progression.

BACKGROUND: Injection drug use is associated with poor HIV outcomes even among persons receiving highly active antiretroviral therapy (HAART), but there are limited data on the relationship between noninjection drug use and HIV disease progression. METHODS: We conducted an observational study of HIV-infected persons entering care between January 1, 1999, and December 31, 2004, with follow-up through December 31, 2005. RESULTS: There were 1,712 persons in the study cohort: 262 with a history of injection drug use, 785 with a history of noninjection drug use, and 665 with no history of drug use; 56% were White, and 24% were females. Median follow-up was 2.1 years, 33% had HAART prior to first visit, 40% initiated first HAART during the study period, and 306 (17.9%) had an AIDS-defining event or died. Adjusting for gender, age, race, prior antiretroviral use, CD4 cell count, and HIV-1 RNA, patients with a history of injection drug use were more likely to advance to AIDS or death than nonusers (adjusted hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.43-2.70, p < .01). There was no statistically significant difference of disease progression between noninjection drug users and nonusers (HR = 1.19, 95% CI = 0.92-1.56, p = .19). An analysis among the subgroup who initiated their first HAART during the study period (n = 687) showed a similar pattern (injection drug users: HR = 1.83, 95% CI = 1.09-3.06, p = .02; noninjection drug users: HR = 1.21, 95% CI = 0.81-1.80, p = .35). Seventy-four patients had active injection drug use during the study period, 768 active noninjection drug use, and 870 no substance use. Analyses based on active drug use during the study period did not substantially differ from those based on history of drug use. CONCLUSIONS: This study shows no relationship between noninjection drug use and HIV disease progression. This study is limited by using history of drug use and combining different types of drugs. Further studies ascertaining specific type and extent of noninjection drug use prospectively, and with longer follow-up, are needed.

Race, kidney disease progression, and mortality risk in HIV-infected persons.

BACKGROUND AND OBJECTIVES: The burden of HIV-associated chronic kidney disease (CKD) is growing in the United States, partially because of increased HIV-infection rates among African Americans. We determined the prevalence, incidence, and risk of rapid estimated GFR (eGFR) decline, ESRD, and death among HIV-infected (HIV+) African-American and non-African-American individuals cared for at the Comprehensive Care Center in Nashville, Tennessee, from January 1, 1998, through December 31, 2005. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Mixed effects, competing risks, and Poisson and Cox regression models were used to assess the risk of rapid eGFR decline (defined as ≥50% decrease in baseline eGFR), CKD5/ESRD, and death. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate eGFR. Confounders were adjusted with a propensity score that related patient characteristics to the probability of being African American. Mixed effects models compared the rate of rapid eGFR decline for HIV-infected African Americans and non-African Americans. RESULTS: There were 2468 HIV-infected individuals in the study: 33% African American; 21% female. Among all patients, HIV-infected African Americans did not have a statistically significant increased risk for rapid eGFR decline compared with non-African Americans. However, African Americans had a significantly higher risk of ESRD and tended toward a higher risk of death. CONCLUSIONS: HIV-infected African Americans did not have a statistically significant difference in the risk of eGFR decline when compared with HIV-infected non-African Americans. The findings in this study have potential public health significance.

Estimating the optimal CD4 count for HIV-infected persons to start antiretroviral therapy.

BACKGROUND: Optimal timing of antiretroviral therapy in HIV-infected persons is unclear, although 2 recent large observational studies have improved our understanding of the best CD4 threshold for initiation. These studies compared the effect of starting HAART on mortality and mortality/AIDS between strata defined using broad ranges of CD4 counts. We sought to expand this understanding using a novel statistical approach proposed by Robins et al. METHODS: Using observational data from 1034 antiretroviral-naive HIV-infected patients from Nashville, Tennessee, we directly estimated the optimal CD4 count for initiation of HAART to maximize patient health 6, 12, 24, and 36 months after the first instance of CD4 falling below 750. We measured health using 2 outcome metrics, one based on CD4 counts at the end of follow-up and the other based on a published quality-of-life scale; both metrics incorporated death, AIDS-defining events, serious non-AIDS events, and CD4 at the end of follow-up, if asymptomatic. RESULTS: The CD4-based metric estimated that to maximize health 6, 12, 24, and 36 months after study entry, HAART should be initiated within 3 months of CD4 first dropping below 495 (95% confidence interval [CI] = 468-522), 554 (459-750), 489 (427-750), and 509 (460-750), respectively. The quality-of-life-based metric produced CD4 initiation threshold estimates of 337 (95% CI = 201-442), 354 (288-386), 358 (294-750), and 475 (287-750) for the same time points. CONCLUSIONS: Our results support early initiation of antiretroviral therapy, although the criterion for starting therapy depends on the choice of health outcome.

Postpartum discontinuation of antiretroviral therapy and risk of maternal AIDS-defining events, non-AIDS-defining events, and mortality among a cohort of HIV-1-infected women in the United States.

This retrospective cohort study of HIV-infected women receiving highly active antiretroviral therapy (HAART) while pregnant assessed the effect of postpartum HAART discontinuation on maternal AIDS-defining events (ADEs), non-AIDS-defining events (non-ADEs), and death 1997-2008 in Nashville, Tennessee. Cox proportional hazards models compared rates of ADE or all-cause death and non-ADE or all-cause death, and competing risks analyses compared rates of ADE or ADE-related death and non-ADE or non-ADE-related death across the groups. There were two groups: women who stopped HAART postpartum (discontinuation, n = 54) and women who continued HAART postpartum (continuation, n = 69). Fifty percent were African American, 40% had prior non-HAART antiretroviral therapy (ART) use, and 38% had a history of illicit drug use. Median age was 27.5 years, baseline CD4(%) was 532 (34%) and CD4 nadir was 332 cells/mm(3), baseline and peak HIV-1 RNA were 2.6 and 4.32 log(10) copies per milliliter, respectively. Women in the continuation group were older, had lower baseline CD4, CD4%, and CD4 nadir, and had higher peak HIV-1 RNA. In multivariable proportional hazards models, the hazard ratios [95% confidence interval (CI)] of ADE or all-cause death and non-ADE or all-cause death were lower in the continuation group, but not statistically significantly: 0.50 (0.12, 2.12; p = 0.35) and 0.69 (0.24, 1.95; p = 0.48), respectively. The results were similar in competing risks analyses. Despite having characteristics associated with worse prognosis, women who continued HAART postpartum had lower hazard ratio point estimates for ADEs or death and non-ADEs or death than women who discontinued HAART. Larger studies with longer follow-up are indicated to assess this association.

Antiretroviral therapy initiation before, during, or after pregnancy in HIV-1-infected women: maternal virologic, immunologic, and clinical response.

BACKGROUND: Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed. METHODS: We conducted a retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30). RESULTS: Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (-0.35 vs. 0.10 log(10) copies/mL, P = 0.03 and 183.8 vs. -70.8 cells/mm(3), P = 0.03, respectively) but similar to those initiating HAART before pregnancy (-0.32 log(10) copies/mL, P = 0.96 and 155.8 cells/mm(3), P = 0.81, respectively). There were 3 (25%) AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4%) in those initiating HAART during pregnancy, and 5 (17%) in those initiating after pregnancy (P = 0.01). There were no statistical differences in rates of HIV disease progression between groups. CONCLUSIONS: HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

Increased detectability of plasma HIV-1 RNA after introduction of a new assay and altered specimen-processing procedures.

After changes to assay and specimen-processing methods, plasma human immunodeficiency virus type 1 (HIV-1) RNA was frequently detectable in patients who previously had well-suppressed HIV-1 RNA levels. This artifact is attributable to shipping frozen plasma in primary plasma preparation tubes and is not caused by the HIV-1 RNA detection assay; it can be avoided by shipping plasma in a secondary tube.