Background Dramatic increases in patients requiring linkage to HIV treatment are anticipated in response to updated CDC HIV testing recommendations advocating routine, opt-out testing. Methods A retrospective analysis nested within a prospective HIV clinical cohort study evaluated patients establishing initial outpatient HIV treatment at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic between 1 January 2000 and 31 December 2005. Survival methods were used to evaluate the impact of missed visits in the first year of care on subsequent mortality in the context of other baseline sociodemographic, psychosocial, and clinical factors. Mortality was ascertained by query of the Social Security Death Index as of 1 August 2007. Results Among 543 study participants initiating outpatient HIV care, 60% missed a visit in the first year. Mortality was 2.3 per 100 person-years for patients who missed visits compared with 1.0 per 100 person-years for those who attended all scheduled appointments during the first year after establishing outpatient treatment (P=0.02). In Cox proportional hazards analysis, higher hazards of death were independently associated with missed visits (HR=2.90, 95%CI=1.28–6.56), older age (HR=1.58 per 10 years, 95%CI=1.12–2.22), and baseline CD4 count <200 cells/mm3 (HR=2.70, 95%CI=1.00–7.30). Conclusions Patients who missed visits in the first year after initiating outpatient HIV treatment had more than twice the rate of long-term mortality relative to those who attended all scheduled appointments. We posit that early missed visits are not causally responsible for the higher observed mortality, but rather identify patients more likely to exhibit health behaviors that portend increased subsequent mortality.

Background Although antiretroviral therapy has the ability to fully restore a normal CD4+ cell count (>500 cells/mm3) in most patients, it is not yet clear whether all patients can achieve normalization of their CD4+ cell count, in part because no study has followed up patients for >7 years. Methods Three hundred sixty-six patients from 5 clinical cohorts who maintained a plasma human immunodeficiency virus (HIV) RNA level ≤1000 copies/mL for at least 4 years after initiation of antiretroviral therapy were included. Changes in CD4+ cell count were evaluated using mixed-effects modeling, spline-smoothing regression, and Kaplan-Meier techniques. Results The majority (83%) of the patients were men. The median CD4+ cell count at the time of therapy initiation was 201 cells/mm3 (interquartile range, 72−344 cells/mm3), and the median age was 47 years. The median follow-up period was 7.5 years (interquartile range, 5.5−9.7 years). CD4+ cell counts continued to increase throughout the follow-up period, albeit slowly after year 4. Although almost all patients (95%) who started therapy with a CD4+ cell count ≥300 cells/mm3 were able to attain a CD4+ cell count ≥500 cells/mm3, 44% of patients who started therapy with a CD4+ cell count <100 cells/mm3 and 25% of patients who started therapy with a CD4+ cell count of 100−200 cells/mm3 were unable to achieve a CD4+ cell count >500 cells/mm3 over a mean duration of follow-up of 7.5 years; many did not reach this threshold by year 10. Twenty-four percent of individuals with a CD4+ cell count <500 cells/mm3 at year 4 had evidence of a CD4+ cell count plateau after year 4. The frequency of detectable viremia (“blips”) after year 4 was not associated with the magnitude of the CD4+ cell count change. Conclusions A substantial proportion of patients who delay therapy until their CD4+ cell count decreases to <200 cells/mm3 do not achieve a normal CD4+ cell count, even after a decade of otherwise effective antiretroviral therapy. Although the majority of patients have evidence of slow increases in their CD4+ cell count over time, many do not. These individuals may have an elevated risk of non–AIDS-related morbidity and mortality.

Following HIV diagnosis, linkage to outpatient treatment, antiretroviral initiation, and longitudinal retention in care represent the foundation for successful treatment. While prior studies have evaluated these processes in isolation, a systematic evaluation of successive steps in the same cohort of patients has not yet been performed. To ensure optimal long-term outcomes, a better understanding of the interplay of these processes is needed. Therefore, a retrospective cohort study of patients initiating outpatient care at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic between January 2000 and December 2005 was undertaken. Multivariable models determined factors associated with: late diagnosis/linkage to care (initial CD4 < 350 cells/mm3), timely antiretroviral initiation, and retention across the first two years of care. Delayed linkage was observed in two-thirds of the overall sample (n = 567) and was associated with older age (odds ratio [OR] 1.31 per 10 years; 95% confidence interval [CI] = 1.06-1.62) and African American race (OR = 2.45; 95% CI = 1.60-3.74). Attending all clinic visits (hazard ratio [HR] = 6.45; 95% CI = 4.47-9.31) and lower initial CD4 counts led to earlier antiretroviral initiation. Worse retention in the first 2 years was associated with younger age (OR = 0.68 per 10 years; 95% CI = 0.56-0.83), higher baseline CD4 count, and substance abuse (OR = 1.78; 95% CI = 1.16-2.73). Interventions to improve timely HIV diagnosis and linkage to care should focus on older patients and African Americans while efforts to improve retention should address younger patients, those with higher baseline CD4 counts, and substance abuse. Missed clinic visits represent an important obstacle to the timely initiation of antiretroviral therapy. These data inform development of interventions to improve linkage and retention in HIV care, an emerging area of growing importance.

These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Background By supplementing an index composed of HIV biomarkers and age (Restricted Index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) Index more completely reflects risk of mortality. We compare the accuracy of the VACS and Restricted Indices 1) among subjects outside the Veterans Healthcare System (VA), 2) over 1–5 years of prior exposure to antiretroviral therapy (ART), and 3) within important patient subgroups. Methods We used data from 13 cohorts in the North American AIDS Cohort Collaboration (NA-ACCORD, n=10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine and hepatitis C status), and survival. We used C statistic and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1–5 years. We then combined VA (n=5,066) and NA-ACCORD data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level. Results Mean follow-up was 3.3 years (655 deaths). Compared with the Restricted Index, the VACS Index showed greater discrimination (C statistic: 0.77 vs. 0.74; NRI 12%; p<0.0001). NRI was highest among those with HIV-1 RNA<500 copies/ml (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups. Conclusion VACS Index scores discriminate risk and translate into accurate mortality estimates over 1–5 years of exposures to ART and for diverse patient subgroups from North American

Background Cancer is increasingly common among HIV patients given improved survival. Objective To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. Design Cohort study Setting North American AIDS Cohort Collaboration on Research and Design during 1996–2009 Patients 86,620 HIV-infected and 196,987 uninfected adults Measurements We estimated cancer-type-specific cumulative incidence by age 75 years by HIV status and calendar era, and examined calendar trends in cumulative incidence and hazard rates. Results Cumulative incidences (%) of cancer by age 75 (HIV+/HIV−) were: Kaposi sarcoma (KS), 4.4/0.01; non-Hodgkin’s lymphoma (NHL), 4.5/0.7; lung, 3.4/2.8; anal, 1.5/0.1; colorectal, 1.0/1.5; liver, 1.1/0.4; Hodgkin lymphoma (HL), 0.9/0.1; melanoma, 0.5/0.6; and oral cavity/pharyngeal, 0.8/0.8. Among HIV-infected subjects, we observed decreasing calendar trends in cumulative incidence and hazard rate for KS and NHL. For anal, colorectal and liver cancers, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (−9% per year), allowing greater opportunity to be diagnosed with these cancer types. Despite decreasing hazard rate trends for lung, HL, and melanoma, we did not observe cumulative incidence trends due to the compensating effect of the declining mortality rate on cumulative incidence. Limitations Secular trends in screening, smoking, and viral co-infections were not evaluated. Conclusions Our analytic approach helped disentangle the effects of improved survival and changing cancer-specific hazard rates on cumulative incidence trends among HIV patients. Cumulative cancer incidence by age 75, approximating lifetime risk in HIV patients, may have clinical utility in this population. The high cumulative incidences by age 75 for KS, NHL, and lung cancer supports early and sustained ART and smoking cessation. Primary Funding Source National Institutes of Health

Background Racial/ethnic health care disparities are well described in people living with HIV/AIDS, although the processes underlying observed disparities are not well elucidated. Methods A retrospective analysis nested in the UAB 1917 Clinic Cohort observational HIV study evaluated patients between August 2004 and January 2007. Factors associated with appointment non-adherence, a proportion of missed outpatient visits, were evaluated. Next, the role of appointment non-adherence in explaining the relationship between African American race and virologic failure (plasma HIV RNA >50 copies/mL) was examined using a staged multivariable modeling approach. Results Among 1,221 participants a broad distribution of appointment non-adherence was observed, with 40% of patients missing at least 1 in every 4 scheduled visits. The adjusted odds of appointment non-adherence were 1.85 times higher in African American patients compared to Whites (95%CI=1.61–2.14). Appointment non-adherence was associated with virologic failure (OR 1.78; 95%CI=1.48–2.13), and partially mediated the relationship between African American race and virologic failure. African Americans had 1.56 times the adjusted odds of virologic failure (95%CI=1.19–2.05), which declined to 1.30 (95%CI=0.98–1.72) when controlling for appointment non-adherence, a hypothesized mediator. Conclusions Appointment non-adherence was more common in African American patients, associated with virologic failure, and appeared to explain part of observed racial disparities in virologic failure.

Nurses and nurse practitioners require information on the health problems faced by aging HIV-infected adults. In this descriptive, cross-sectional study, we reviewed the electronic medical records of 1,478 adult patients seen in an HIV clinic between May 2006 and August 2007 to examine patterns of comorbidities, and immunological and clinical characteristics across each decade of life. With increasing age, patients were found to have lower HIV viral loads, more prescribed medications, and a higher prevalence of comorbid conditions, including coronary artery disease, hypertension, hypercholesterolemia, hypogonadism, erectile dysfunction, diabetes, peripheral neuropathy, hepatitis C, esophageal gastric reflux disease, and renal disease. Fortunately, with increasing age, patients were also more likely to have public or private health insurance and tended to be more compliant to medical appointments. With growing interest in aging with HIV, this study highlights the vastly different comorbidity profiles across decades of life, calling into question what constitutes "older" with HIV.