Myocardial Steatosis Among Antiretroviral Therapy-Treated People With Human Immunodeficiency Virus Participating in the REPRIEVE Trial.

BACKGROUND: People with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants. METHODS: Eighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content. RESULTS: Median (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count < 350 cells/mm³ (P = .055). Age and BMI ≥ 25 kg/m2 were additionally associated with increased odds of markedly increased IMTG content (P = .049 and P = .046, respectively). CONCLUSIONS: A substantial proportion of antiretroviral therapy-treated PWH exhibited myocardial steatosis. Age, BMI ≥ 25 kg/m2, low nadir CD4 count, and history of IVDU emerged as possible risk factors for myocardial steatosis in this group. CLINICAL TRIALS REGISTRATION: NCT02344290; NCT03238755.

Effect of Short-Term Antiretroviral Therapy Interruption on Levels of Integrated HIV DNA.

Analytic treatment interruption (ATI) studies are required to evaluate strategies aimed at achieving ART-free HIV remission, but the impact of ATI on the viral reservoir remains unclear. We validated a DNA size selection-based assay for measuring levels of integrated HIV DNA and applied it to assess the effects of short-term ATI on the HIV reservoir. Samples from participants from four AIDS Clinical Trials Group ATI studies were assayed for integrated HIV DNA levels. Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained for 12 participants with available samples pre-ATI and approximately 6 months after ART resumption. Four participants also had samples available during the ATI. The median duration of ATI was 12 weeks. Validation of the HIV integrated DNA size-exclusion (HIDE) assay was performed using samples spiked with unintegrated HIV DNA, HIV-infected cell lines, and participant PBMCs. The HIDE assay eliminated 99% of unintegrated HIV DNA species and strongly correlated with the established Alu-gag assay. For the majority of individuals, integrated DNA levels increased during ATI and subsequently declined upon ART resumption. There was no significant difference in the levels of integrated HIV DNA between the pre- and post-ATI time points, with a median ratio of post- to pre-ATI HIV DNA levels of 0.95. Using a new integrated HIV DNA assay, we found minimal change in the levels of integrated HIV DNA in participants who underwent an ATI, followed by 6 months of ART. This suggests that short-term ATI can be conducted without a significant impact on the levels of integrated proviral DNA in the peripheral blood.IMPORTANCE Interventions aimed at achieving sustained antiretroviral therapy (ART)-free HIV remission require treatment interruption trials to assess their efficacy. However, these trials are accompanied by safety concerns related to the expansion of the viral reservoir. We validated an assay that uses an automated DNA size-selection platform for quantifying levels of integrated HIV DNA and is less sample- and labor-intensive than current assays. Using stored samples from AIDS Clinical Trials Group studies, we found that short-term ART discontinuation had minimal impact on integrated HIV DNA levels after ART resumption, providing reassurance about the reservoir effects of short-term treatment interruption trials.

Genome sequence of Listeria monocytogenes 07PF0776, a cardiotropic serovar 4b strain.

Listeria monocytogenes is a food-borne bacterial pathogen commonly associated with serious invasive infections of the central nervous system or of the developing fetus. We present the genome sequence of Listeria monocytogenes 07PF0776, a serovar 4b isolate from a human myocardial abscess that exhibits enhanced invasion of cardiac tissue.

Similar efficacy of raltegravir when used with or without a protease inhibitor in treatment-experienced patients.

BACKGROUND: Patients with multiclass-resistant HIV-1 have limited treatment options. Raltegravir, an inhibitor of integrase, has shown excellent efficacy when used with protease inhibitors (Pis) in patients with drug-resistant HIV-1. Limited data are available however about the outcomes when using raltegravir without Pis in this population. METHODS: Medical records of subjects who received raltegravir as part of the Merck EAP study 0518 were reviewed and abstracted at participating sites. Eligibility criteria included HIV positivity, age ≥ 16 years, limited or no treatment options due to resistance or intolerance to multiple antiretroviral regimens, detectable viremia on current treatment regimen, and documented resistance to at least one drug in each antiretroviral class (PI, NNRTI, and nucleoside analogue). Demographic, clinical, and laboratory data were collected locally using a standardized collection form. Genotypic susceptibility scores (GSS) were determined from the most recent genotypic resistance test available prior to the initiation of raltegravir. The main objective was to compare virologic results in patients who received raltegravir with a PI versus those who received raltegravir without a PI. RESULTS: Four hundred forty-two subjects were evaluated from the respective sites in the EAP trial, of whom 340 were evaluable. The baseline mean HIV RNA was 4.6 log copies/ mL, and the mean CD4 cell count was 159 cells/µL. The median number of total and new antiretroviral agents in the background regimen was 4 and 2, respectively. Among the 254 patients who received a PI, the most common PI used was darunavir (89%). Etravirine was commonly used in both groups: 39% of the PI group and 67% of the non-PI group. At week 12, 67% of PI patients and 64% of non-PI patients achieved HIV RNA <75 copies/mL and 85% and 86%, respectively, achieved HIV RNA <400 copies/mL GSS, which was similar in both groups at baseline, predicted achieving an HIV RNA of <400 and 75 copies/mL at week 12 (P < .05). CONCLUSIONS: In treatment-experienced patients, the combination of raltegravir with a regimen not containing a PI (used with etravirine in two-thirds of patients) had similar virologic activity when compared to more standard regimens using raltegravir with a PI. The main determinant of efficacy was the number of active drugs as measured by GSS. These data expand the potential utility of raltegravir in patients with multidrug-resistant HIV.

Frequency of post treatment control varies by antiretroviral therapy restart and viral load criteria.

Clinical trials including an analytical treatment interruption (ATI) are vital for evaluating the efficacy of novel strategies for HIV remissions. We briefly describe an interactive tool for predicting viral rebound timing in ATI trials and the impact of posttreatment controller (PTC) definitions on PTC frequency estimates. A 4-week viral load threshold of 1000 cps/ml provides both high specificity and sensitivity for PTC detection. PTC frequency varies greatly based on the definition of a PTC.

Low prevalence of primary HIV resistance in western Massachusetts.

Most studies of primary antiretroviral (ARV) resistance have been conducted in large metropolitan areas with reported rates of 8% to 25%. We collected data on 99 HIV-1-infected antiretroviral-naive patients from several sites in Springfield, MA, who underwent genotypic resistance assay between 2004 and 2008. Only major resistance mutations per International AIDS Society-USA (IAS-USA) drug resistance mutations list were considered. The prevalence of resistance was 5% (5 of 99). Three patients had one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation: 103N, 103N, and 190A, 1 patient had a protease inhibitor (PI) mutation: 90M; and 1 patient had 3-class resistance with NNRTI: 181C, 190A, PI: 90M, and nucleoside analogue reverse transcriptase inhibitor (NRTI): 41L, 210W. Mean time from HIV diagnosis to resistance testing was shorter in patients with resistance versus those without: 9 (range 0.3-42 months) versus 27 (range 0.1-418 months), P = .11. There was a trend to lower mean CD4 count in those with resistance, 170 versus 318 cells/mm(3), P = .06. No differences were noted in gender, age, HIV risk category, or HIV RNA level. The low prevalence of primary resistance may be explained by differences in demographic and risk factors or may reflect the time from infection to resistance testing. Our findings emphasize the importance of continued resistance surveillance.

Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease.

CONTEXT: Guidelines recommend antibiotic therapy for acute exacerbations of chronic obstructive pulmonary disease (COPD), but the evidence is based on small, heterogeneous trials, few of which include hospitalized patients. OBJECTIVE: To compare the outcomes of patients treated with antibiotics in the first 2 hospital days with those treated later or not at all. DESIGN, SETTING, AND PATIENTS: Retrospective cohort of patients aged 40 years or older who were hospitalized from January 1, 2006, through December 31, 2007, for acute exacerbations of COPD at 413 acute care facilities throughout the United States. MAIN OUTCOME MEASURES: A composite measure of treatment failure, defined as the initiation of mechanical ventilation after the second hospital day, inpatient mortality, or readmission for acute exacerbations of COPD within 30 days of discharge; length of stay, and hospital costs. RESULTS: Of 84,621 patients, 79% received at least 2 consecutive days of antibiotic treatment. Treated patients were less likely than nontreated patients to receive mechanical ventilation after the second hospital day (1.07%; 95% confidence interval [CI], 1.06%-1.08% vs 1.80%; 95% CI, 1.78%-1.82%), had lower rates of inpatient mortality (1.04%; 95% CI, 1.03%-1.05% vs 1.59%; 95% CI, 1.57%-1.61%), and had lower rates of readmission for acute exacerbations of COPD (7.91%; 95% CI, 7.89%-7.94% vs 8.79%; 95% CI, 8.74%-8.83%). Patients treated with antibiotic agents had a higher rate of readmissions for Clostridium difficile (0.19%; 95% CI, 0.187%-0.193%) than those who were not treated (0.09%; 95% CI, 0.086%-0.094%). After multivariable adjustment, including the propensity for antibiotic treatment, the risk of treatment failure was lower in antibiotic-treated patients (odds ratio, 0.87; 95% CI, 0.82-0.92). A grouped treatment approach and hierarchical modeling to account for potential confounding of hospital effects yielded similar results. Analysis stratified by risk of treatment failure found similar magnitudes of benefit across all subgroups. CONCLUSION: Early antibiotic administration was associated with improved outcomes among patients hospitalized for acute exacerbations of COPD regardless of the risk of treatment failure.

Choriocarcinoma in an AIDS patient--relapsing but not fatal.

Choriocarcinoma is associated with high mortality in immunocompromised patients, in contrast to a good prognosis in immunocompetent individuals. Respiratory failure due to metatstatic choriocarcinoma is associated with high mortality in any patient. We report a case of a woman with AIDS that survived metastatic choriocarcinoma and respiratory failure. We also observed that in contrast to some in vitro studies, the markedly elevated levels of beta-subunit of human chorionic gonadotropin in this patient did not have any apparent inhibitory effect on viral replication.

Extended-Release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living With HIV With Opioid Use Disorders Transitioning to the Community: Results of a Double-Blind, Placebo-Controlled Randomized Trial.

OBJECTIVE: To determine whether extended-release naltrexone (XR-NTX) would improve or maintain viral suppression (VS) among prisoners or jail detainees with HIV and opioid use disorder (OUD) transitioning to the community. DESIGN: A 4-site, prospective randomized double-blind, placebo-controlled trial was conducted among prison and jail inmates with HIV and OUD transitioning to the community from September 2010 through March 2016. METHODS: Eligible participants (N = 93) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 66) or placebo (n = 27) starting at release and observed for 6 months. The primary outcome was the proportion that maintained or improved VS (<50 copies/mL) from baseline to 6 months. RESULTS: Participants allocated to XR-NTX significantly improved to VS (<50 copies/mL) from baseline (37.9%) to 6 months (60.6%) (P = 0.002), whereas the placebo group did not (55.6% at baseline to 40.7% at 6 months P = 0.294). There was, however, no statistical significant difference in VS levels at 6 months between XR-NTX (60.6%) vs. placebo (40.7%) (P = 0.087). After controlling for other factors, only allocation to XR-NTX (adjusted odds ratio = 2.90; 95% confidence interval = 1.04 to 8.14, P = 0.043) was associated with the primary outcome. Trajectories in VS from baseline to 6 months differed significantly (P = 0.017) between treatment groups, and the differences in the discordant values were significantly different as well (P = 0.041): the XR-NTX group was more likely than the placebo group to improve VS (30.3% vs. 18.5%), maintain VS (30.3% vs. 27.3), and less likely to lose VS (7.6% vs. 33.3%) by 6 months. CONCLUSIONS: XR-NTX improves or maintains VS after release to the community for incarcerated people living with HIV with OUD.

Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection.

BACKGROUND: We evaluated the efficacy and safety of oral posaconazole for human immunodeficiency virus (HIV)-infected subjects with oropharyngeal candidiasis (OPC) and/or esophageal candidiasis (EC) who were clinically refractory to treatment with oral fluconazole or itraconazole. METHODS: Subjects with confirmed OPC or EC who did not improve after receiving standard courses of fluconazole or itraconazole treatment were eligible for study enrollment. Subjects received either oral posaconazole (400 mg twice daily) for 3 days followed by oral posaconazole (400 mg once daily) for 25 days (regimen A; 103 patients) or oral posaconazole (400 mg twice daily) for 28 days (regimen B; 96 patients). The primary end point was cure or improvement after 28 days. Primary efficacy analyses were performed on the subset of treated subjects with refractory disease (e.g., baseline culture positive for fluconazole- or itraconazole-resistant Candida species or persistent or progressive clinical signs or symptoms consistent with treatment failure). RESULTS: Of the modified intent-to-treat population, 132 (75%) of 176 subjects achieved a clinical response to posaconazole treatment. Clinical response rates were similar between regimen A recipients (75.3%) and regimen B recipients (74.7%). Clinical responses occurred in 67 (73%) of 92 subjects with baseline isolates resistant to fluconazole, 49 (74%) of 66 subjects with baseline isolates resistant to itraconazole, and 42 (74%) of 57 subjects with isolates resistant to both. Clinical response was achieved in 32 (74.4%) of 43 subjects with endoscopically documented EC. The most common treatment-related adverse events were diarrhea (11%), neutropenia (7%), flatulence (6%), and nausea (6%). Eight subjects (4%) discontinued therapy as a result of a treatment-related adverse event. CONCLUSIONS: Posaconazole offers a safe and effective treatment option for HIV-infected subjects with azole-refractory OPC and/or EC.

Treatment Trends and Outcomes in Healthcare-Associated Pneumonia.

BACKGROUND: The American Thoracic Society and Infectious Diseases Society of America guidelines for management of healthcare-associated pneumonia (HCAP), first published in 2005, have been controversial regarding the selection of empiric broad-spectrum antibiotics, whether the criteria for HCAP predicts the likelihood of infection with multidrug resistant organisms, and whether HCAP patients have improved outcomes when treated with empiric broad-spectrum antibiotics. METHODS: A retrospective cohort study at 488 US hospitals from July 2007 to November 2011. Patients who met criteria for HCAP were included. Guideline-concordant antibiotics were assessed based on guideline recommendations. We assessed changes in hospital rates of concordant antibiotic use over time and their correlation with outcomes. RESULTS: Among 149,963 patients with HCAP, 19.6% received fully guideline-concordant antibiotics, 21.7% received partially concordant antibiotics, and 58.9% received discordant antibiotics. Guideline concordance increased over time. Rates of fully or partially concordant antibiotics varied across hospitals (median 36.4%; interquartile range 25.8%-49.1%). Among patients who received discordant antibiotics, 81.5% were treated according to community-acquired pneumonia (CAP) guidelines. On average, the rate of guideline concordance increased by 2.2% per 6-month interval, while hospital level rates of mortality, excess length of stay, and progression to respiratory failure did not change. CONCLUSIONS: In this large, nationally representative cohort, only 1 in 5 patients with risk factors for HCAP received treatment that was fully in accordance with guidelines, and many received CAP therapy instead. At the hospital level, increases in the use of concordant antibiotics were not associated with declines in mortality, excess length of stay, or progression to respiratory failure.

A multicenter randomized trial evaluating posaconazole versus fluconazole for the treatment of oropharyngeal candidiasis in subjects with HIV/AIDS.

BACKGROUND: Oropharyngeal candidiasis is the most common opportunistic infection among persons infected with human immunodeficiency virus (HIV). Use of some agents is hampered by lack of efficacy, emergence of resistance, adverse events, and need for intravenous administration. Posaconazole is an extended-spectrum triazole with potent in vitro activity against Candida species, including Candida albicans, Candida glabrata, and Candida krusei (including fluconazole-resistant strains). METHODS: This multicenter, randomized, evaluator-blinded study of subjects with HIV infection and oropharyngeal candidiasis compared efficacy of posaconazole with that of fluconazole. Subjects received either 200 mg of posaconazole or fluconazole oral suspension on day 1, followed by 100 mg/day for 13 days. The primary study end point--clinical success (cure or improvement) on day 14--was evaluated for 329 subjects. Durability of clinical success was evaluated on day 42. RESULTS: Three hundred fifty subjects received posaconazole (n = 178) or fluconazole (n = 172). Clinical success occurred in 155 (91.7%) of 169 posaconazole recipients and in 148 (92.5%) of 160 fluconazole recipients (95% confidence interval, -6.61% to 5.04%), indicating that posaconazole was not inferior to fluconazole. On day 14, mycological success was 68% in both arms, but by day 42, significantly more posaconazole recipients than fluconazole recipients continued to have mycological success (40.6% vs. 26.4%; P=.038). Fewer posaconazole recipients than fluconazole recipients experienced clinical relapse (31.5% vs. 38.2%). Adverse events were similar between treatment arms. CONCLUSIONS: Results demonstrate that posaconazole was as effective as fluconazole in producing a successful clinical outcome. However, posaconazole was more effective in sustaining clinical success after treatment was stopped.

Investigation of Efavirenz Discontinuation in Multi-ethnic Populations of HIV-positive Individuals by Genetic Analysis.

BACKGROUND: Efavirenz (EFV) based antiretroviral therapy is expanding worldwide. However discontinuation of EFV containing regimens is common in some patients, particularly black patients, due most often to neuropsychiatric side effects. These adverse drug effects often result in premature drug discontinuation, as well as considerable morbidity. METHODS: We genotyped CYP2A6, CYP2B6 and CYP3A4, which encode enzymes principally involved in EFV metabolism, from patients enrolled in the multinational SMART, FIRST and ESPRIT studies, for whom outcome data of treatment adherence was available. Patients with loss or decrease of function single nucleotide polymorphisms (SNPs) in the above genes were assigned a risk score based upon the number of SNPs present weighted relative to whether CYP2B6 (main metabolism pathway) and/or CYP2A6 and CYP3A4 (accessory pathways) were involved. Cox regression models were used to study the association between high genetic risk and time from initiation to EFV discontinuation. Failure was defined as discontinuation of an antiretroviral regimen other than for virologic failure or protocol determined discontinuation. FINDINGS: Patients with highest pharmacogenetic risk, as defined by cumulative SNPs in CYP2A6, CYP2B6 and CYP3A4, have an increased risk of discontinuation of EFV containing therapy compared to patients with lower genetic risk scores (adjusted HR 1.9, 95% CI 1.2, 3.1, P = 0.009). High genetic risk score was not associated with an increased risk of discontinuing atazanavir or nevirapine. High genetic risk was present more often in blacks compared to non-blacks (Adjusted OR 4.5, 95% CI: 1.9,10.5), and treatment discontinuation was also increased in blacks overall (Adjusted HR 1.4, 95% CI 1.0, 1.9). However, high genetic risk was more associated with treatment discontinuation than race alone for both blacks (Adjusted OR 1.9, 95% CI 0.8, 4.8) and non-blacks (Adjusted OR 5.3, 95% CI 1.5, 18.0). INTERPRETATION: Premature discontinuation of ART delays the time to effective long term viral suppression, and is associated with significant morbidity. Pharmacogenetic testing may predict those with a high risk of EFV discontinuation, and therefore should be considered in patients in whom initiation of EFV based ART is being considered. FUNDING: Funded by NIH.

Survival is prolonged by highly active antiretroviral therapy in AIDS patients with primary central nervous system lymphoma.

OBJECTIVE: To determine the effects of highly active antiretroviral therapy (HAART) on survival in AIDS-related primary central nervous system lymphoma (PCNSL). METHODS: Survival in consecutive patients with PCNSL at a large county teaching hospital from 1995 to 2001 were analyzed by the log rank test and Cox proportional hazards ratios (HR) were calculated for factors potentially affecting survival. RESULTS: During the study period, 25 patients were diagnosed with PCNSL: 19 definite and 6 probable. At diagnosis, median CD4 cell count was 12 x 10(6) cells/l (range 1-151) and median HIV viral load was 5.3 log(10) copies/ml (range 3.9-5.9). Sixteen patients died (median survival 87 days; range, 0 to > 2112). Longer survival was noted for patients who received HAART after diagnosis [HR for death, 0.06; 95% confidence interval (CI), 0.01-0.48]. Six of seven HAART-treated patients were alive versus 0/18 untreated patients at a median follow-up time of 667 days (P = 0.0007 by log rank test). A survival benefit was seen for patients who had >/= 0.5 log(10) copies/ml decrease in HIV viral load after diagnosis (n = 6; HR, 0.07; 95% CI, 0.01-0.55) and for patients with a significant CD4 cell rebound (increase >/= 50 x 106 cells/l) in response to HAART (n = 6): all survived versus 0/19 survived (P = 0.0003). Cranial radiation therapy (n = 13) prolonged survival (HR, 0.20; 95% CI, 0.07-0.58). Median survival was only 29 days for 11 patients who received neither radiation nor HAART. CONCLUSIONS: Receipt of HAART after diagnosis is associated with a significantly longer survival in patients with AIDS-related CNS lymphoma.

Focal neurological disease in patients with acquired immunodeficiency syndrome.

Focal neurological disease in patients with acquired immunodeficiency syndrome may be caused by various opportunistic pathogens and malignancies, including Toxoplasma gondii, progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV), and Epstein-Barr virus-related primary central nervous system (CNS) lymphoma. Diagnosis may be difficult, because the findings of lumbar puncture, computed tomography (CT), and magnetic resonance imaging are relatively nonspecific. Newer techniques have led to improved diagnostic accuracy of these conditions. Polymerase chain reaction (PCR) of cerebrospinal fluid specimens is useful for diagnosis of PML, CNS lymphoma, and CMV encephalitis. Recent studies have indicated the diagnostic utility of new neuroimaging techniques, such as single-photon emission CT and positron emission tomography. The combination of PCR and neuroimaging techniques may obviate the need for brain biopsy in selected cases. However, stereotactic brain biopsy, which is associated with relatively low morbidity rates, remains the reference standard for diagnosis. Highly active antiretroviral therapy has improved the prognosis of several focal CNS processes, most notably toxoplasmosis, PML, and CMV encephalitis.

Changes in mortality related to human immunodeficiency virus infection: comparative analysis of inpatient deaths in 1995 and in 1999-2000.

We conducted a retrospective chart review of human immunodeficiency virus (HIV)-infected patients who died in 1995 and in 1999-2000. We found an increase in the proportion of patients who died from an illness that was not related to acquired immunodeficiency syndrome (AIDS). Although there was a decrease in the prevalence of AIDS-defining illnesses, >85% of patients died with CD4 counts of <200 cells/microL. The leading cause of death was Pneumocystis carinii pneumonia (PCP). Nonadherence to therapy and new diagnosis of HIV infection were the leading reasons why patients were not receiving antiretroviral therapy. The leading causes of non-AIDS-related deaths in 1999-2000 were non-AIDS-defining infections and end-stage liver disease. At our hospital, PCP remains an important cause of death in the highly active antiretroviral therapy (HAART) era, possibly because >50% of HIV-infected patients who died were not receiving HAART. AIDS-defining illnesses continue to be a major cause of mortality in the HAART era in populations where access to care and adherence to HAART is limited.

Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy.

We performed a prospective observational study to assess the safety of stopping maintenance therapy for disseminated histoplasmosis among human immunodeficiency virus infected patients after response to antiretroviral therapy. All subjects received at least 12 months of antifungal therapy and 6 months of antiretroviral therapy before entry. Negative results of fungal blood cultures, urine and serum Histoplasma antigen level of <4.1 units, and CD4+ T cell count of >150 cells/mm3 were required for eligibility. Thirty-two subjects were enrolled; the median CD4+ T cell count at study entry was 289 cells/mm3. No relapses of histoplasmosis occurred after a median duration of follow-up of 24 months. This corresponded to an observed relapse rate of 0 cases per 65 person-years. The median CD4+ T cell count at final study visit was 338 cells/mm3. Discontinuation of antifungal maintenance therapy appears to be safe for patients with acquired immunodeficiency syndrome with previously treated disseminated histoplasmosis and sustained immunologic improvement in response to antiretroviral therapy.

CMV pp65 antigen testing is of limited utility in the diagnosis of concomitant CMV disease in HIV-infected patients in the HAART era.

BACKGROUND: There are limited data on the utility of the CMV pp65 antigen (Ag) test for the diagnosis of concomitant CMV end-organ disease (EOD) in HIV+ patients in the highly active antiretroviral therapy era. OBJECTIVES: We sought to assess the predictive value of a single pp65 test for the diagnosis of concomitant CMV EOD in HIV-infected patients. STUDY DESIGN: A review of all pp65 Ag tests conducted at a large county teaching hospital from January 1998 through July 1999 was conducted. A diagnosis of CMV EOD required histopathologic evidence (except for retinitis). Concomitant disease was defined as CMV EOD within 30 days of Ag test. Results were reported as number of Ag positive cells/300000 cells counted. RESULTS: Two-hundred and thirty patient charts (308 antigen tests) were reviewed. The median follow-up time was 334 days. Thirty-two patients had a prior diagnosis of CMV EOD. The most common reasons for testing were fever (45), pneumonia (10), and monitoring for recurrent retinitis (8). Ag tests were positive (range 1-1042 cells) in 51 patients. Twelve patients were diagnosed with concomitant CMV EOD. A diagnosis other than CMV was made in a significant majority of patients (154). The mean initial pp65 level was significantly higher in patients with concomitant CMV EOD versus those without concomitant CMV: 314 cells versus 13 cells, P<0.0001. The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 67, 81, 16 and 98%, respectively. Using a 50-cell cutoff and including only patients with CMV symptoms and CD4<100, improved test accuracy: sensitivity, specificity, PPV, and NPV of 60, 91, 60, and 91%. The CD4 cell count but not the HIV viral load was predictive of CMV EOD. CONCLUSIONS: The CMV pp65 Ag test is useful in excluding concomitant CMV disease, but has limited utility in the diagnosis of acute CMV disease. The highest test utility will be in patients with a high likelihood of CMV disease based on symptoms, and CD4 cell count.

Comparison of the effects of acute influenza infection and Influenza vaccination on HIV viral load and CD4 cell counts.

PURPOSE: Influenza vaccination is recommended for HIV-infected patients, although the efficacy is not clear. Prior studies have yielded differing results with regard to the effects of influenza vaccination on HIV viral load and CD4 cell counts. The effects of acute influenza on HIV viral replication and CD4 cell counts have not been well described. We sought to assess the effect of influenza infection and vaccination on HIV viral load and CD4 cell counts. SUBJECTS AND METHODS: All cases of influenza occurring in HIV-infected individuals over 3 years at a large county hospital were reviewed. For the year 1997-1998, data on all HIV clinic patients who were vaccinated for influenza were recorded prospectively. In order to assess the effects of influenza infection (Group I) and vaccination (Group II) on HIV viral load and CD4 cell counts, values from before and after influenza infection or vaccination were compared to each other and to a matched control group not vaccinated and without influenza infection (Group III). RESULTS: Forty-three cases of influenza were diagnosed. Pre- and post-influenza viral load in Group I was not significantly different: 3.34 versus 3.49 log copies/ml (P=0.36). Viral load was unchanged in 22 of 37 patients, increased in ten patients and decreased in five patients. Similarly, pre- and post-vaccination viral load in Group II was not significantly different: 3.52 versus 3.66 log copies/ml (P=0.12). Thirty-four of 47 patients who received influenza vaccine had no significant change in viral load-viral load increased in ten patients and decreased in three patients. No significant CD4 cell count changes were noted following influenza infection or vaccination. In contrast, Group III patients experienced a small decline in viral load from 4.23 to 3.39 log copies/ml, P<0.05, while there was a trend towards an increase in CD4 cell counts (P=0.06). CONCLUSIONS: Following influenza infection or vaccination, most patients did not have a significant increase in HIV viral load or decrease in CD4 cell count.

Linezolid-Induced anemia and thrombocytopenia.

Linezolid, a fluorinated oxazolidinone, is the first of a new class of antimicrobials designed to target resistant gram-positive cocci. Hematologic adverse effects, including reversible thrombocytopenia, were reported during phase III comparator-controlled trials. A 66-year-old man developed sternal osteomyelitis due to methicillin-resistant Staphylococcus aureus after undergoing coronary artery bypass graft surgery. Methicillin-resistant S. aureus bacteremia developed after several surgical debridements and courses of vancomycin failed to improve the patient's condition. Oral linezolid 600 mg twice/day was begun; 17 days later, a complete blood count revealed that his hematocrit had decreased from 37.4% to 24.8%, and his platelet count had decreased from 234 x 10(3)/mm3 to 149 x 10(3)/mm3. Both values returned to normal after linezolid was discontinued. Complete blood counts should be monitored closely in patients taking linezolid, especially if therapy continues for more than 14 days.