Mari M. Kitahata

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

To evaluate psychometric characteristics and cross-sectional and longitudinal validity of the 7-item PROMIS® Fatigue Short Form and additional fatigue items among people living with HIV (PLWH) in a nationally distributed network of clinics collecting patient reported data at the time of routine clinical care. Cross-sectional and longitudinal fatigue data were collected from September 2012 through April 2013 across clinics participating in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). We analyzed data regarding psychometric characteristics including simulated computerized adaptive testing and differential item functioning, and regarding associations with clinical characteristics. We analyzed data from 1597 PLWH. Fatigue was common in this cohort. Scores from the PROMIS® Fatigue Short Form and from the item bank had acceptable psychometric characteristics and strong evidence for validity, but neither performed better than shorter instruments already integrated in CNICS. The PROMIS® Fatigue Item Bank is a valid approach to measuring fatigue in clinical care settings among PLWH, but in our analyses did not perform better than instruments associated with less respondent burden.

We assessed CD4 count at initial presentation for HIV care among ≥50-year-olds from 1997-2007 in 13 US and Canadian clinical cohorts and compared to 3) and 95% confidence intervals ([,]) were determined using linear regression stratified by age category and adjusted for gender, race/ethnicity, HIV transmission risk and cohort. From 1997-2007, the proportion of individuals presenting for HIV care who were ≥50-years-old increased from 17% to 27% (p-value < 0.01). The median CD4 count among ≥50 year-olds was consistently lower than younger adults. The interaction of age group and calendar year was significant (p-value 3; ≥50-year-olds: 7[5 , 9] cells/mm³), after adjusting for sex, race/ethnicity, HIV transmission risk group and cohort; however, increases in the two groups were similar after 2000. A greater proportion of older individuals had an AIDS-defining diagnosis at, or within three months prior to, first presentation for HIV care compared to younger individuals (13% vs. 10%, respectively). Due to the increasing proportion, consistently lower CD4 counts, and more advanced HIV disease in adults ≥50-year-old at first presentation for HIV care, renewed HIV testing efforts are needed.

The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

Highly active antiretroviral therapy (HAART) delays disease progression and death.^1–4 However, the treatments incompletely control HIV replication,^5–7 only partially restore immune function,^8,9 have significant short- and long-term toxicities,^10–14 and eventually fail in many patients with consequent development of HIV drug resistance.⁶ Thus, there is increasing need for information to guide HIV-infected patients and their providers in making decisions regarding optimal use of antiretroviral therapies. Although clinical trials provide valuable information about efficacy and side effects of antiretroviral treatment, they have limited size, duration and power to detect effects on clinical outcomes, focusing instead on surrogate endpoints such as virologic failure, treatment discontinuation or composite outcome measures.¹⁵

Although adherence to HAART at a level above 95% has been associated with optimal viral suppression, the impact of different levels of adherence on long-term clinical outcomes has not been determined. We used an objective pharmacy-based measure to examine the association between three levels of adherence to HAART and disease progression among a population-based cohort of HIV-infected patients attending an urban HIV specialty clinic. Higher levels of adherence to HAART were significantly associated with longer time to virologic failure ( P < 0.001), greater increase in CD4 cell count ( P = 0.04), and lower risk of progression to clinical AIDS or death ( P < 0.007). After controlling for other factors, patients with low adherence had over five times the risk of disease progression than patients with moderate adherence ( P = 0.007) or patients with high adherence ( P = 0.001). There was no significant difference in the risk of progression between patients with moderate and high levels of adherence ( P > 0.2). Patients who progressed to AIDS or death had significantly higher viral loads ( P = 0.01) and lower CD4 cell counts ( P = 0.03) than patients who experienced virologic failure, but did not progress.

We conducted a prospective study of an electronic clinical reminder system in an academic medical center-based human immunodeficiency virus (HIV) spe

OBJECTIVE: It has been shown that greater physician experience in the care of persons with AIDS prolongs survival, but how more experienced primary care physicians achieve better outcomes is not known. DESIGN/SETTING/PATIENTS: Retrospective cohort study of HIV-infected patients enrolled in a large staff-model health maintenance organization from 1990 through 1999. MEASUREMENTS: Adjusted odds of medical service delivery and adjusted hazard ratio of death by physician experience level (least, moderate, most) and service utilization. MAIN RESULTS: Primary care delivery by physicians with greater AIDS experience was associated with improved survival. After controlling for disease severity, patients cared for by the most experienced physicians were twice as likely to receive a primary care visit in a given month compared with patients of the least and moderately experienced physicians (P<.01). Patients of the least experienced physicians received the lowest level of outpatient pharmacy and laboratory services (P<.001) and were half as likely to have a specialty care visit compared with patients of the most and moderately experienced physicians (P<.05). Patients who received infrequent primary care visits by the least experienced physicians were 15.3 times more likely to die than patients of the most experienced physicians (P=.02). There was a significant increase in primary care services delivered to the population of HIV-infected patients receiving care in 1999, when highly active antiretroviral therapy (HAART) was in general use, compared with the time period prior to the introduction of HAART. CONCLUSIONS: Primary care delivery by physicians with greater HIV experience contributes to improved patient outcomes.

Recent advances in antiretroviral therapy have led to effective but increasingly complex strategies for the treatment of HIV infection. In a previous study, we demonstrated that physicians' experience in the care of patients with AIDS improves survival. We conducted this study to determine whether greater physician experience is associated with earlier adoption and appropriate use of new antiretroviral treatment regimens. Retrospective medical record review of a population-based sample of HIV-infected individuals who received antiretroviral treatment between December 1995 and May 1997 by primary care physicians practicing throughout the state of Washington. We classified antiretroviral regimens observed into one of four categories based on national treatment guidelines. The use of new antiretroviral treatment regimens significantly increased during the study period; 22% of patients were treated with a protease inhibitor (PI)-based regimen or an alternative PI- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen between December 1995 and November 1996, compared with 57% between April and May 1997 (p < .001). After controlling for CD4 count and the calendar period of treatment, patients cared for by physicians with greater HIV experience were significantly more likely to receive PI-based regimens or alternative PI- or NNRTI-based antiretroviral regimens (p = .02). Use of PI-based regimens was also associated with lower CD4 count (p < .001) and treatment after January 1997 (p = .02), but independent of patient demographic characteristics and the geographic location of physicians' practices. Greater physician experience in the care of persons with HIV infection is associated with earlier adoption of new antiretroviral treatment regardless of whether physicians practice in a rural or urban area.