Acquired Immunodeficiency Syndrome: Currier JS

Dubé MP, Sprecher D, Henry WK, Aberg JA, Torriani FJ, Hodis HN, Schouten J, Levin J, Myers G, Zackin R, Nevin T, Currier JS, Anonymous00022. · Indiana University, Indianapolis, IN 46202, USA. · Clin Infect Dis. · Pubmed #11073755 No free full text.

Abstract: Dyslipidemia is a prevalent condition that affects patients infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy. These preliminary recommendations summarize the current understanding in this area and propose guidelines for management. Existing guidelines for the management of dyslipidemia in the general population formed the general basis for our recommendations. Data on the prevalence and treatment of dyslipidemia of HIV-infected patients, implications of treatment-related dyslipidemia in other chronically ill populations, and pharmacokinetic profiles for the available hypolipidemic agents in non-HIV populations were considered. Although the implications of dyslipidemia in this population are not fully known, the frequency, type, and magnitude of lipid alterations in HIV-infected people are expected to result in increased cardiovascular morbidity. We propose that these patients undergo evaluation and treatment on the basis of existing guidelines for dyslipidemia, with the caveat that avoidance of interactions with antiretroviral agents is paramount.

Tsibris AM, Paredes R, Chadburn A, Su Z, Henrich TJ, Krambrink A, Hughes MD, Aberg JA, Currier JS, Tashima K, Godfrey C, Greaves W, Flexner C, Skolnik PR, Wilkin TJ, Gulick RM, Kuritzkes DR. · Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Clin Infect Dis. · Pubmed #19191652 No free full text.

Abstract: BACKGROUND: Lack of functional CCR5 increases the severity of certain viral infections, including West Nile virus and tickborne encephalitis. In a phase II trial of the investigational CCR5 antagonist vicriviroc (AIDS Clinical Trials Group protocol A5211), 4 lymphomas occurred in study patients who received vicriviroc. Because of the known association between unregulated Epstein-Barr virus (EBV) replication and lymphoma in immunocompromised patients, we evaluated whether vicriviroc exposure was associated with lymphoma EBV antigen positivity and/or had an effect on plasma levels of EBV DNA. METHODS: Clinical findings for all 4 patients enrolled in the A5211 study who developed lymphoma (2 Hodgkin and 2 non-Hodgkin) were reviewed, and tumor specimens were assessed for evidence of ongoing EBV replication. Longitudinal plasma samples from 116 patients in the A5211 study were analyzed, and EBV DNA was quantified by real-time polymerase chain reaction. RESULTS: Plasma EBV DNA was not detected in the 2 patients with non-Hodgkin lymphoma; both patients with Hodgkin lymphoma who had samples tested had EBV DNA levels <3200 copies/mL. One patient with Hodgkin lymphoma had a lymph node core biopsy specimen that was strongly positive for EBV; the other 3 lymphomas were histochemically EBV negative. None of the 116 patients with available samples experienced sustained increases in plasma EBV levels. CONCLUSIONS: CCR5 antagonism by vicriviroc treatment in treatment-experienced patients was not associated with reactivation of EBV infection.

Hammer SM, Bassett R, Squires KE, Fischl MA, Demeter LM, Currier JS, Mellors JW, Morse GD, Eron JJ, Santana JL, DeGruttola V, Anonymous00160. · Columbia University, New York, NY, USA. · Antivir Ther. · Pubmed #14760884 No free full text.

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Lederman HM, Williams PL, Wu JW, Evans TG, Cohn SE, McCutchan JA, Koletar SL, Hafner R, Connick E, Valentine FT, McElrath MJ, Roberts NJ, Currier JS, Anonymous00072. · Eudowood Division of Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · J Infect Dis. · Pubmed #14673757 No free full text.

Abstract: Immune function was observed for 144 weeks in 643 human immunodeficiency virus (HIV)-infected subjects who (1) had nadir CD4+ cell counts of <50 cells/mm3, followed by a sustained increase to > or =100 cells/mm3 after the initiation of HAART, and (2) were enrolled in a randomized trial of continued azithromycin prophylaxis versus withdrawal for prevention of Mycobacterium avium complex disease. The median CD4+ cell count was 226 cells/mm3 at entry and 358 cells/mm3 at week 144. Anergy (80.2% of patients) and lack of lymphoproliferative response to tetanus toxoid (TT; 73%) after immunization and impaired antibody responses after receipt of hepatitis A (54%) and TT (86%) vaccines were considered to be evidence of impaired immune reconstitution. Receipt of azithromycin did not have an effect on CD4+ cell count but was associated with higher rates of delayed-type hypersensitivity responses to TT (25% of subjects who received azithromycin vs. 15% of those who did not; P=.009) and mumps skin test antigen (29% vs. 17%; P=.001). Although the subjects had only partial responses to immune function testing, the rate of opportunistic infections was very low, and none of the tests was predictive of risk.

Benson CA, Williams PL, Currier JS, Holland F, Mahon LF, MacGregor RR, Inderlied CB, Flexner C, Neidig J, Chaisson R, Notario GF, Hafner R, Anonymous00005. · Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA. · Clin Infect Dis. · Pubmed #14557969 No free full text.

Abstract: This multicenter, randomized, open-label phase 3 clinical trial compared the safety and efficacy of 3 clarithromycin-containing combination regimens for the treatment of disseminated Mycobacterium avium complex (MAC) disease in persons with acquired immunodeficiency syndrome. A total of 160 eligible patients with bacteremic MAC disease were randomized to receive clarithromycin with either ethambutol (C+E), rifabutin (C+R), or both (C+E+R) for 48 weeks. After 12 weeks of treatment, the proportion of subjects with a complete microbiologic response was not statistically significantly different among treatment arms: the proportion was 40% in the C+E group, 42% in the C+R group, and 51% in the C+E+R group (P=.454). The proportion of patients with complete or partial responses who experienced a relapse while receiving C+R (24%) was significantly higher than that of patients receiving C+E+R (6%; P=.027) and marginally higher than that of patients receiving C+E (7%; P=.057). Subjects in the C+E+R group had improved survival, compared with the C+E group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23-0.83) and the C+R group (HR, 0.49; 95% CI, 0.26-0.92).

Micheletti RG, Fishbein GA, Currier JS, Singer EJ, Fishbein MC. · Department of Medicine, Division of Infectious Diseases, University of California at Los Angeles, Los Angeles, CA 90035, USA. · Mod Pathol. · Pubmed #18536656 No free full text.

Abstract: Two well-recognized patterns of calcification occur in large- and medium-sized arteries, intimal calcification associated with atherosclerosis and medial calcification described by Mönckeberg. Calcification limited to the internal elastic lamina is a third pattern of calcification not previously reported in coronary arteries. Here we describe 19 cases of coronary artery internal elastic lamina calcification. We serially sectioned and examined the coronary arteries of 66 patients with advanced AIDS and 27 HIV- controls with other chronic illnesses. We observed calcification of the internal elastic lamina in 10 HIV+ patients and 9 controls. HIV- patients with internal elastic lamina calcification were significantly older than HIV- patients without it (P=0.008) and HIV+ patients with it (P=0.006). Occasionally, calcification encroached on adjacent intimal or medial tissue with mild fibrosis. There was frequent disruption of the internal elastic lamina but no evidence of inflammation. Calcification was the dominant histologic feature in all cases. Von Kossa, Alizarin red, and trichrome/elastic stains confirmed these findings. Patients with internal elastic lamina calcification often had extensive medical histories but did not suffer from chronic renal failure or other conditions known to cause calcium dysregulation. We describe coronary internal elastic lamina calcification in HIV+ patients and older HIV- adults. The clinical significance of this finding is unknown. It could lead to arterial stiffening and increased pulse pressure and could be mistaken for intimal calcification on coronary imaging. Internal elastic lamina calcification may result from premature aging due to HIV disease and chronic illness or from metabolic disorders in HIV+ patients.

Micheletti RG, Fishbein GA, Fishbein MC, Singer EJ, Weiss RE, Jeffries RA, Currier JS. · University of California, Los Angeles, Los Angeles, CA, USA. · Cardiovasc Pathol. · Pubmed #18402832 No free full text.

Abstract: BACKGROUND: Studies suggest human immunodeficiency virus-positive (HIV+) patients have an increased risk of coronary artery disease (CAD), yet little is known about the histopathology, severity, or distribution of lesions. METHODS: The coronary arteries of 66 deceased AIDS patients and 19 HIV controls (age <55) were dissected and graded for percent luminal stenosis by intimal lesions, percent of intima involved with lipid, and extent of intimal calcification on a scale of 0 to 3. Medical histories, antiretroviral therapies, and CAD risk factors were reviewed. RESULTS: HIV+ patients were older than controls (P=.06), and more were male (P=.02). Thirty-five percent of HIV+ patients had stenosis >or=75% of at least one artery. Compared to controls, HIV+ patients had three times greater odds of stenosis >or=75%, controlling for age and sex (one-sided P=.03). Older age and male sex were also risk factors (one-sided P<.001). HIV seropositivity was associated with increased plaque lipid content (one-sided P=.02) and calcification (one-sided P=.08). Duration of HIV infection, antiretroviral therapy, and immune status did not predict severe disease in multivariate analyses. Previously unreported patterns of dystrophic calcification were observed in HIV+ patients and older controls. CONCLUSIONS: Young to middle-aged patients dying from advanced AIDS have atherosclerotic CAD that may result in luminal narrowing, heavy calcification, and high plaque lipid content. The pattern of disease, location of lesions, and plaque composition are typical of atherosclerosis in HIV-negative patients. No relationship between antiretroviral therapies and atherosclerosis was seen in this small study of heavily treated patients.

Cohn SE, Kammann E, Williams P, Currier JS, Chesney MA. · Infectious Diseases Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY, 14642, USA. · Clin Infect Dis. · Pubmed #11915003 No free full text.

Abstract: High-level adherence to regimens of combination antiretroviral therapy and prophylactic medications for opportunistic infections (OIs) is crucial to their success. However, little is known about the association between adherence to these life-sustaining therapies and such clinical outcomes as progression of acquired immune deficiency syndrome (AIDS) or development of OIs. We assessed adherence to regimens of antiretroviral and Mycobacterium avium complex (MAC) prophylactic medications in 643 patients enrolled in a trial of MAC prophylaxis. By week 56 of the study follow-up, 42% of the patients reported nonadherence to MAC prophylaxis, whereas one-quarter of the patients reported nonadherence to potent antiretroviral regimens. Nonadherence to both MAC prophylaxis and antiretroviral therapy was associated with higher human immunodeficiency virus (HIV) type 1 RNA levels and a significant increase in the risk of developing an AIDS-defining complication or death. Predictors of nonadherence are presented. These results underscore the clinical significance of adherence to HIV therapy and may be helpful in designing interventions to optimize the management of HIV by improving adherence.

Grinspoon SK, Grunfeld C, Kotler DP, Currier JS, Lundgren JD, Dubé MP, Lipshultz SE, Hsue PY, Squires K, Schambelan M, Wilson PW, Yarasheski KE, Hadigan CM, Stein JH, Eckel RH. · No affiliation provided · Circulation. · Pubmed #18566320 links to  free full text

This publication has no abstract.