Susan E. Buskin

Bordetella bronchiseptica Infection in Human Immunodeficiency Virus-Infected Patients

Bordetella bronchiseptica is a pleomorphic gram-negative coccobacillus that commonly causes respiratory tract infections in dogs. We identified nine human immunodeficiency virus (HIV)-infected persons with culture-confirmed B. bronchiseptica infections (eight respiratory tract and one disseminated infection). The respiratory illnesses ranged in severity from mild upper respiratory tract infection to pneumonia. All nine patients had had at least one AIDS-defining condition before the B. bronchiseptica infection. Two patients had household contact with dogs before their illnesses, and one had household contact with cats. Infection due to B. bronchiseptica is uncommon in HIV-infected persons. Additional data are needed to fully define the spectrum of disease due to B. bronchiseptica infections and to evaluate the possibility that this infection may be acquired from pets. Treatment of B. bronchiseptica infection should be tailored to the patient and should be based on the results of susceptibility testing.

Trends in perimortal conditions and mortality rates among HIV-infected patients.

Objectives:To describe trends in perimortal conditions (pathological conditions causing death or present at death but not necessarily the reported cause of death) during three periods related to the availability of HAART, pre-HAART (1992–1995), early HAART (1996–1999), and contemporary HAART (2000–2003); annual mortality rates; and antiretroviral therapy (ART) prevalence during 1992–2003. Design:Multicenter observational clinical cohort in the United States (Adult/Adolescent Spectrum of HIV Disease [ASD] project). Methods:Proportionate mortality for selected perimortal conditions, annual mortality rates, and ART prevalence were standardized by sex, race/ethnicity, age at death, HIV transmission category, and lowest CD4 cell count of ASD decedents. Multivariable generalized linear regression was used to estimate trends in proportionate mortality, as linear trends through all three HAART periods, mortality rates, and ART prevalence. Results:Of 9225 deaths, 58.6% occurred during 1992–1995, 29.5% during 1996–1999, and 11.9% during 2000–2003. Linear trends in proportionate mortality for noninfectious diseases (e.g., liver disease, hypertension, and alcohol abuse) increased significantly; proportionate mortality for AIDS-defining infectious diseases (e.g., pneumocystosis, nontuberculous mycobacterial disease, and cytomegalovirus disease) decreased significantly. Mortality rates decreased from 487.5/1000 person-years in 1995 to 100.6 in 2002. Of 36 256 patients from ASD, 75.7% (standardized average) were prescribed ART annually. Conclusions:Among HIV-infected patients, the majority of whom were prescribed ART, the increasing trend in common noninfectious perimortal conditions support screening and treatment for these conditions in order to sustain the trend in declining mortality rates.

Differences in prescription of antiretroviral therapy in a large cohort of HIV-infected patients.

The objective of this study was to determine factors associated with prescription of highly active antiretroviral therapy (HAART). The authors observed 9530 patients eligible for antiretroviral therapy (ART) in more than 100 hospitals and clinics in 10 US cities. Multiple logistic regression analysis was used to assess factors associated with HAART prescription, stratifying patients by no history versus history of ART to assess the association between prescription and CD4, viral load, and outpatient visits. Overall, female gender (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.60–0.76) and alcoholism (OR, 0.85; 95% CI, 0.74–0.99) were associated with decreased likelihood of HAART prescription. Enrollment at a private facility (OR, 1.33; 95% CI, 1.14–1.56), heterosexual exposure (OR, 1.34; 95% CI, 1.13–1.58), and Hispanic ethnicity (OR, 1.19; 95% CI, 1.04–1.37) were associated with prescription. For patients with no history of prescribed ART, CD4 <500 cells/&mgr;L (OR, 3.94; 95% CI, 2.02–7.66), and high viral load were associated with increased likelihood of prescription; for patients with history of ART prescription, those whose outpatient visits averaged ≥2 per 6-month interval (OR, 1.30; 95% CI, 1.10–1.54) were more likely and those with high viral load were less likely to be prescribed HAART (OR, 0.50; 95% CI, 0.44–0.56). The authors found differences in HAART prescription by gender, race, exposure mode, alcoholism, and provider type for all patients, by CD4 and viral load for patients with no history of ART prescription, and by average number of outpatient visits and viral load for patients with history of ART prescription.

Profile of Patients With Kaposi's Sarcoma in the Era of Highly Active Antiretroviral Therapy

PURPOSE Since the advent of highly active antiretroviral therapy (HAART), the incidence of Kaposis sarcoma (KS) among AIDS patients has declined both nationwide and in King County, Washington. We sought to compare clinical parameters of patients diagnosed with KS in the pre-HAART (1990 to 1996) and HAART (1997 to 2002) eras. METHODS We used patient data abstracted from the Adult/Adolescent Spectrum of HIV-Related Diseases study of Public Health-Seattle and King County. RESULTS Patients diagnosed with KS in the HAART era (n = 40) were significantly more likely (P < .05) than pre-HAART-era KS patients (n = 366) to be diagnosed with alcohol problems (43% v 18%), noninjection drug use (45% v 18%), injection drug use (25% v 10%), psychosis (25% v 13%), and hypertension (13% v 2%). Although median CD4(+) count and HIV-1 viral load at the time of KS diagnosis were not significantly different between the two groups, significantly fewer (P < .01) HAART-era KS patients developed opportunistic illnesses (OIs) during their follow-up. The risk of dying among KS patients diagnosed in the HAART era is significantly lower (P < .01) than for KS patients diagnosed in the pre-HAART era (hazard ratio, 0.24). CONCLUSION Although HAART-era KS patients in King County were as likely to have a depleted CD4(+) cell count and high HIV-1 viral loads at the time of KS diagnosis as pre-HAART KS patients, they survived longer and fewer of them were diagnosed with other OIs. They also had an increased prevalence of substance abuse and mental illness, contributing to a dynamic and changing KS clinical profile.

Ongoing Risk Behavior Among Persons With HIV in Medical Care

We surveyed randomly selected patients in the largest HIV clinic in Seattle, WA in 2005 and 2006. A total of 397 patients completed usable surveys. Twenty-seven percent of men who have sex with men (MSM) and 22% of women or heterosexual men reported having non-concordant unprotected anal or vaginal intercourse in the preceding year. Compared to 2005, more MSM in 2006 reported meeting a sex partner via the Internet (15% vs. 33%), and fewer met partners in bathhouses (23% vs. 13%). Twenty-four percent of MSM reported deciding not to have sex with a potential partner because he was HIV negative, and 31% of MSM reported that another man had decided not to have sex with them because they were HIV positive. Among all participants, 22% had told a sex partner they were HIV negative since their HIV diagnosis. These findings demonstrate the persistence of high-risk behavior among persons with HIV, a rapid increase in the use of the Internet among MSM to find sex partners, and provide direct evidence for serosorting among MSM.

When to Begin Highly Active Antiretroviral Therapy? Evidence Supporting Initiation of Therapy at CD4+ Lymphocyte Counts <350 cells/µL

We assessed the risk of acquired immunodeficiency syndrome (AIDS)-related opportunistic illness or death among persons first prescribed highly active antiretroviral therapy (HAART) in January 1996 or later in the Centers for Disease Control and Preventions Adult and Adolescent HIV Spectrum of Disease Project. Patients were included if they were naive to antiretroviral drugs and had no history of AIDS-related opportunistic illness. Risk was assessed as a function of CD4+ lymphocyte count and human immunodeficiency virus load at the time of initiation of HAART in a Cox proportional hazards model. Hazard ratios for AIDS or death were 6.3, 3.5, and 1.7 for persons with baseline CD4+ cell counts of 0-49, 50-199, and 200-349 cells/microL, respectively, compared with the referent (CD4+ cell count > or =500 cells/microL). HAART should not be deferred until the CD4+ cell count reaches <200 cells/microL. The increased hazard associated with CD4+ cell counts of 200-349 cells/microL was modest but supports initiation of HAART at CD4+ cell counts <350 cells/microL, particularly in patients with high virus loads.

Use of and Adherence to Antiretroviral Therapy in a Large U.S. Sample of HIV-infected Adults in Care, 2007-2008

Background: Antiretroviral therapy (ART) is the cornerstone of HIV clinical care and is increasingly recognized as a key component of HIV prevention. However, the benefits of ART can be realized only if HIV-infected persons maintain high levels of adherence. Methods: We present interview data (collected from June 2007 through September 2008) from a national HIV surveillance system in the United States—the Medical Monitoring Project (MMP)—to describe persons taking ART. We used multivariate logistic regression to assess behavioral, sociodemographic, and medication regimen factors associated with three measures that capture different dimensions of nonadherence to ART: dose, schedule, and instruction. Results: The use of ART among HIV-infected adults in care was high (85%), but adherence to ART was suboptimal and varied across the three measures of nonadherence. Of MMP participants currently taking ART, the following reported nonadherence during the past 48 hours: 13% to dose, 27% to schedule, and 30% to instruction. The determinants of the three measures also varied, although younger age and binge drinking were associated with all aspects of nonadherence. Conclusion: Our results support the measurement of multiple dimensions of medication-taking behavior in order to avoid overestimating adherence to ART.

Dramatic increase in preexposure prophylaxis use among MSM in Washington state.

Objective:HIV preexposure prophylaxis (PrEP) is efficacious, but uptake has been slow. In Washington State, most insurance plans, including Medicaid, pay for PrEP, and the state supports a PrEP drug assistance program. We assessed trends in PrEP awareness and use among MSM in Washington. Design and setting:Serial cross-sectional survey conducted annually at the Seattle Pride Parade between 2009 and 2015. Methods:In a convenience sample of MSM who reside in Washington State and deny ever testing HIV positive (n = 2168), we evaluated the association between calendar year and self-report of PrEP uptake and awareness using descriptive statistics and multivariable relative risk and logistic regression. Regression models included HIV risk and demographic covariates. Results:In 2015, 23% [95% confidence interval (CI): 16%, 31%] of high-risk MSM reported currently taking PrEP. The percentage of high-risk MSM who reported ever taking PrEP increased from 5% in 2012 to 31% in 2015. PrEP use among lower-risk MSM was low and stable, between 1 and 3% in 2012–2015. In multivariable analyses, PrEP use was associated with later calendar years (2015 vs. 2012: adjusted relative risk = 2.29, 95% CI: 1.16, 4.52) and elevated HIV risk (adjusted relative risk = 2.92, 95% CI: 2.00, 4.25). The percentage of high and lower-risk MSM who had heard of PrEP increased from 13 to 86% and from 29 to 58%, respectively. Conclusion:PrEP awareness is high and the use has rapidly increased over the last year among MSM in Seattle, Washington, USA. These findings demonstrate that high levels of PrEP use can be achieved among MSM at high-risk for HIV infection.

Electronic Human Immunodeficiency Virus (HIV) Clinical Reminder System Improves Adherence to Practice Guidelines among the University of Washington HIV Study Cohort

We conducted a prospective study of an electronic clinical reminder system in an academic medical center-based human immunodeficiency virus (HIV) specialty clinic. Published performance indicators were used to examine adherence to HIV practice guidelines before and after its implementation for 1204 patients. More than 90% of patients received CD4 cell count and HIV type 1 (HIV-1) RNA level monitoring every 3-6 months during both time periods, and approximately 80% of patients with a CD4 cell count nadir of <350 cells/mm(3) received highly active antiretroviral therapy. Patients were significantly more likely to receive prophylaxis against Mycobacterium avium complex (hazard ratio, 3.84; 95% confidence interval [CI], 1.58-9.31; P=.003), to undergo annual cervical carcinoma screening (OR, 2.09; 95% CI, 1.04-4.16; P=.04), and to undergo serological screening for Toxoplasma gondii (odds ratio [OR], 1.86; 95% CI, 1.05-3.27; P=.03) and syphilis infection (OR, 3.71; 95% CI, 2.37-5.81; P<.0001). HIV clinical reminders delivered at the time that HIV care is provided were associated with more timely initiation of recommended practices.

Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013.

BACKGROUND US guidelines recommend genotyping for persons newly diagnosed with HIV infection to identify transmitted drug resistance mutations associated with decreased susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. To date, testing for integrase strand transfer inhibitor (INSTI) mutations has not been routinely recommended. We aimed to evaluate the prevalence of transmitted INSTI mutations among persons with primary HIV-1 infection in Seattle, WA, USA. METHODS Persons with primary HIV-1 infection have enrolled in an observational cohort at the University of Washington Primary Infection Clinic since 1992. We performed a retrospective analysis of plasma specimens collected prospectively from the 82 antiretroviral-naive subjects who were enrolled from 2007-2013, after FDA-approval of the first INSTI. Resistance testing was performed by consensus sequencing. RESULTS Specimens for analysis had been obtained a median of 24 (IQR 18-41, range 8-108) days after the estimated date of HIV-1 infection. All subjects were infected with HIV-1 subtype B except for one subject infected with subtype C. Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H). Using exact binomial CIs, the upper bound of the 95% CI was 4.4%. CONCLUSIONS Although our sample size was small, this study does not support the need at this time to evaluate integrase mutations as part of routine consensus sequencing among persons newly diagnosed with HIV-1 infection. However, it is likely that the prevalence of transmitted INSTI mutations may increase with the recent commercial introduction of additional INSTIs and presumably greater INSTI use among persons living with HIV-1.