Lori E. Fantry

Gastrointestinal infections in the immunocompromised host.

The gastrointestinal tract is a common site of infection in the opportunistic host. Pathogens range from highly virulent organisms, which infect people with well functioning immune systems as well as people with poorly functioning immune systems, to opportunistic organisms, which infect only those with impaired immune systems. Viruses, bacteria, fungi, and protozoa lead to disease that can be especially severe, debilitating, and difficult to treat in the immunocompromised host. Yet in this era of highly active antiretroviral therapy for HIV-infected patients and strategies to reduce immunosuppression in transplant and oncology patients, appropriate diagnostic tests and treatment can both improve the quality of life and decrease mortality. In this article, I review the changing pathogenesis, epidemiology, clinical presentation, diagnosis, and treatment of gastrointestinal infections in the immunocompromised host.

A comparison of Qt and a-vO2 in individuals with HIV taking and not taking HAART

PURPOSE The aim of this study was to determine whether highly active antiretroviral therapy (HAART), rather than the direct effect of HIV infection, limits peripheral muscle oxygen extraction-utilization (a-vO(2)) in individuals infected with the human immunodeficiency virus (HIV). METHODS Fifteen subjects (6 female and 9 male) with HIV taking HAART, 15 subjects infected with HIV not taking HAART, and 15 healthy gender and activity level matched non-HIV infected controls (N = 45) performed an maximal treadmill exercise test to exhaustion. Noninvasive cardiac output Qt was measured at each stage and at peak exercise using the indirect Fick method based on the exponential rise carbon dioxide rebreathing method. Intergroup comparisons were adjusted for interactions of peak oxygen consumption ([V02), body surface area, and [V02]t using ANCOVA. RESULTS Peak a-vO(2) was significantly lower (P < 0.05) in subjects with HIV taking HAART (10.0 +/- 0.5 vol%) compared with subjects with HIV not taking HAART (11.7 +/- 0.5 vol%) and noninfected controls (12.7 +/- 0.5 vol%). In subjects with HIV taking HAART, peak heart rate (HR) (170.5 +/- 3.9 bpm) was lower than (P < 0.05) and stroke volume (Vs) (123.0 +/- 3.9 mL x beat-1) at peak exercise was higher (P < 0.05) than subjects with HIV not taking HAART (179.9 +/- 3.5 bpm) (106.6 +/- 3.9 mL x beat-1) and noninfected controls (185.4 +/- 3.8 bpm) (100.6 +/- 4.0 mL.beat-1) upon ANCOVA. There were no significant differences in peak [VO2]t between groups. CONCLUSION Peak a-vO(2) was diminished in subjects infected with HIV taking HAART compared with HIV-infected subjects not taking HAART and noninfected controls matched for age, gender, and physical activity level. Findings of the current study implicated HAART as a primary contributor to decreased muscle oxygen extraction-utilization in individuals infected with HIV.

Immunologic and virologic analyses of an acutely HIV type 1-infected patient with extremely rapid disease progression

The immunologic and virologic factors that impact on the rate of disease progression after acute infection with human immunodeficiency virus (HIV) type 1 are poorly understood. A patient with an extraordinarily rapid disease course leading to AIDS-associated death within 6 months of infection was studied intensively for the presence of anti-HIV immune reactivities as well as changes in the genetic and biologic properties of virus isolates. Although altered humoral responses were evident, the most distinctive immunologic feature was a nearly complete absence of detectable HIV-specific CTL responses. In addition to a rapid decline in CD3+CD4+ cells, elevated percentages of CD8+CD45RA+ and CD8+CD57+ cells and diminished CD8+CD45R0+ and CD8+CD28+ cells were evident. Primary viral isolates recovered throughout the course of infection exhibited limited sequence diversity. Cloned viral envelopes were found to have unusually broad patterns of coreceptor usage for cell-cell fusion, although infectivity studies yielded no evidence of infection via these alternative receptors. The infectivity studies demonstrated that these isolates and their envelopes maintained an R5 phenotype throughout the course of disease. The absence of demonstrable anti-HIV CTL reactivities, coupled with a protracted course of seroconversion, highlights the importance of robust HIV-specific immune responses in the control of disease progression.

Decreased peak arteriovenous oxygen difference during treadmill exercise testing in individuals infected with the human immunodeficiency virus

OBJECTIVE To determine if arteriovenous oxygen difference was lower in asymptomatic individuals with human immunodeficiency virus (HIV) infection than in sedentary but otherwise healthy controls. DESIGN Quasi-experimental cross-sectional. SETTING Clinical exercise laboratory. PARTICIPANTS Fifteen subjects (10 men, 5 women) with HIV and 15 healthy gender- and activity level-matched controls (total N=30). INTERVENTION Participants performed an incremental maximal exercise treadmill test to exhaustion. Electrocardiogram, metabolic, and noninvasive cardiac output measurements were evaluated at rest and throughout the tests. Data were analyzed by using analysis of covariance. MAIN OUTCOME MEASURES Peak oxygen consumption (Vo(2)), cardiac output, stroke volume, and arteriovenous oxygen difference. The arteriovenous oxygen difference was determined indirectly using the Fick equation. RESULTS Peak VO(2) was significantly lower (P<.0005) in participants with HIV (24.6+/-1.2mL.kg(-1).min(-1)) compared with controls (32.0+/-1.2mL.kg(-1).min(-1)). There were no significant intergroup differences in cardiac output or stroke volume at peak exercise. Peak arteriovenous oxygen difference was significantly lower (P<.04) in those infected with HIV (10.8+/-0.5 volume %) than in controls (12.4+/-0.5 volume %). CONCLUSION The observed deficit in aerobic capacity in the participants with HIV appeared to be the result of a peripheral tissue oxygen extraction or utilization limitation. In addition to deconditioning, potential mechanisms for this significant attenuation may include HIV infection and inflammation, highly active antiretroviral therapy medication regimens, or a combination of these factors.

High cancer-related mortality in an urban, predominantly African-American, HIV-infected population.

Objective:To determine mortality associated with a new cancer diagnosis in an urban, predominantly African–American, HIV-infected population. Design:Retrospective cohort study. Methods:All HIV-infected patients diagnosed with cancer between 1 January 2000 and 30 June 2010 were reviewed. Mortality was examined using Kaplan–Meier estimates and Cox proportional hazards models. Results:There were 470 cases of cancer among 447 patients. Patients were predominantly African–American (85%) and male (79%). Non-AIDS-defining cancers (NADCs, 69%) were more common than AIDS-defining cancers (ADCs, 31%). Cumulative cancer incidence increased significantly over the study period. The majority (55.9%) was taking antiretroviral therapy (ART) at cancer diagnosis or started afterward (26.9%); 17.2% never received ART. Stage 3 or 4 cancer was diagnosed in 67%. There were 226 deaths during 1096 person years of follow-up, yielding an overall mortality rate of 206 per 1000 person years. The cumulative mortality rate at 30 days, 1 year, and 2 years was 6.5, 32.2, and 41.4%, respectively. Mortality was similar between patients on ART whether they started before or after the cancer diagnosis but was higher in patients who never received ART. In patients with a known cause of death, 68% were related to progression of the underlying cancer. Conclusion:In a large cohort of urban, predominantly African–American patients with HIV and cancer, many patients presented with late-stage cancer. There was substantial 30-day and 2-year mortality, although ART had a significant mortality benefit. Deaths were most often caused by progression of cancer and not from another HIV-related or AIDS-related event.

Protease inhibitor-associated diabetes mellitus: a potential cause of morbidity and mortality.

Protease Inhibitor-Associated Diabetes Mellitus: A Potential Cause of Morbidity and Mortality Lori Fantry; JAIDS Journal of Acquired Immune Deficiency Syndromes

Vertigo and Abacavir

Vertigo can cause significant morbidity and make a person unable to perform activities of daily life. A human immunodeficiency virus (HIV)-infected patient experienced vertigo while taking abacavir that resolved immediately on cessation of therapy. The mechanism by which abacavir appeared to be associated with vertigo in this patient is unknown.

Anal Cancer Screening in an Urban HIV Clinic: Provider Perceptions and Practice.

In this article, we sought to understand the perceptions and practice of providers on anal cancer screening in HIV-infected patients. Providers in an academic outpatient HIV practice were surveyed. Data were analyzed to determine the acceptability and perceptions of providers on anal Papanicolaou tests. Survey response rate was 55.3% (60.7% among male and 47.4% among female providers). One-third of the providers had received screening requests from patients. Female providers had higher self-rated comfort with anal Papanicolaou tests, with a mean score of 7.1 (95% confidence interval [CI] 4.7-9.5) compared to 3.6 (95% CI 1.5-5.7) for male providers, P = .02. Sixty-seven percent of male providers and 37.5% of female providers would like to refer their patients for screening rather than perform the test themselves. Only 54.2% of our providers have ever performed anal cytology examination. Our survey revealed that not all providers were comfortable performing anal cancer screening for their patients.

Elevated suppressor of cytokine signaling-1 (SOCS-1): a mechanism for dysregulated osteoclastogenesis in HIV transgenic rats.

Accelerated bone loss leading to osteopenia, osteoporosis, and bone fracture is a major health problem that is increasingly common in human immunodeficiency virus (HIV)-infected patients. The underlying pathogenesis is unclear but occurs in both treatment naïve and individuals receiving antiretroviral therapies. We developed an HIV-1 transgenic rat that exhibits many key features of HIV disease including HIV-1-induced changes in bone mineral density (BMD). A key determinant in the rate of bone loss is the differentiation of osteoclasts, the cells responsible for bone resorption. We found HIV-1 transgenic osteoclast precursors (OCP) express higher levels of suppressor of cytokine signaling-1 (SOCS-1) and TNF receptor-associated factor 6 (TRAF6) and are resistant to interferon-gamma (IFN-γ) mediated suppression of osteoclast differentiation. Our data suggest that dysregulated SOCS-1 expression by HIV-1 transgenic OCP promotes osteoclastogenesis leading to the accelerated bone loss observed in this animal model. We propose that elevated SOCS-1 expression in OCP antagonizes the inhibitory effects of IFN-γ and enhances receptor activator of NF-kB ligand (RANKL) signaling that drives osteoclast differentiation and activation. Understanding the molecular mechanisms of HIV-associated BMD changes has the potential to detect and treat bone metabolism disturbances early and improve the quality of life in patients.

Prevalence of Asymptomatic Bacterial Sexually Transmitted Infections in Hospitalized HIV Patients in Baltimore City

Sexually transmitted infections (STIs) are known to promote the transmission of HIV. Diagnosing these infections can identify patients engaging in high-risk behaviors and provides an opportunity for intervention and education. The Centers for Disease Control and Prevention (CDC) recommends STI screening as part of routine HIV care. Ninety HIV-infected inpatients admitted to the University of Maryland Hospital were screened for gonorrhea, chlamydia, and syphilis. None of the nucleic acid amplification probes were positive for gonorrhea, and 1 was positive for chlamydia. A total of 8 rapid plasma reagin (RPR) tests were positive, 2 of which are believed to be associated with new infection or treatment failure. Rapid plasma reagin positivity was found to be associated with men who have sex with men (MSM), low CD4 count, and high HIV viral load. Routine inpatient screening for asymptomatic STIs in HIV-infected patients may be beneficial, particularly patients not engaged in routine outpatient care.