Potentially preventable tuberculosis among HIV-infected persons in the era of highly active antiretroviral treatment.

OBJECTIVE: To characterize the proportion of tuberculosis (TB) cases that could have been prevented among human immunodeficiency virus (HIV) infected persons receiving care in the era of highly active antiretroviral treatment (HAART). DESIGN: We conducted an observational cohort study among HIV-infected patients with >or=2 out-patient visits at the Comprehensive Care Center, Nashville, Tennessee, USA, between 1 January 1998 and 31 December 2005. METHODS: A potentially preventable TB case was defined as a case in which the patient received no screening tuberculin skin test (TST) prior to TB diagnosis or a case in which a patient with a positive screening TST did not complete treatment for latent infection. RESULTS: Of 3601 HIV-infected persons in care (13 905 person-years [p-y] of follow-up), 29 developed TB (230/100,000 p-y). Of the 29, 20 (69%) had not had TST performed as part of routine screening. Of the nine patients screened, four had a positive test, three of whom completed treatment for latent TB infection. Of 29 TB cases, 21 (72%) were therefore potentially preventable. CONCLUSIONS: Most TB cases in this cohort were potentially preventable had the patients undergone a screening TST followed by treatment of latent infection if they had a positive TST.

Low-dose daily subcutaneous interleukin-2 in combination with highly active antiretroviral therapy in HIV+ patients: a randomized controlled trial.

PURPOSE: Previous studies with intermittent interleukin-2 (IL-2) therapy using intermediate and high levels of IL-2 have demonstrated significant increases in the CD4 + T cell count in HIV-infected patients. Intermittent regimens are amenable to outpatient use, but severe adverse events are frequently experienced with intermediate- and high-dose levels of IL-2. Therefore in this study, the effect of daily, subcutaneous low-dose IL-2 therapy on safety and immunological endpoints was investigated to determine whether immunological benefit could be achieved without toxicity in HIV-infected patients also receiving highly active antiretroviral therapy (HAART). METHOD: A total of 115 patients were enrolled in the trial. Fifty-six asymptomatic HIV-infected patients who had CD4 + T cell counts less than 300 cells/microL at screening and a stable HIV viral load received low-dose IL-2 (1.2 million IU [MIU]/m 2 beginning dose) once daily in conjunction with HAART (IL-2 group). Fifty-nine patients received HAART alone (control group). RESULTS: A dramatic effect of IL-2 on the natural killer (NK) cell population was observed with mean increases of 156 cells/microL in the IL-2 group compared to 19.93 cells/microL in the control group (p <.001). Additionally, IL-2-treated patients experienced a statistically significant increase in the mean percentage of CD4 + T cells (3.52% increase) when compared to control patients (1.33% increase) (p <.001). The expanded CD4 + T cell population was primarily of the naive phenotype, with mean increases of 4.53% for the IL-2 group and 0.31% for the control group (p <.001 for between-group difference). In addition, a higher proportion of IL-2-treated patients (67%) compared to control patients (33%) achieved increases of greater than 50% in the CD4+ T cell count (p =.08). Adverse events of grade 3 or grade 4 toxicity were infrequent in the current study and were substantially lower by comparison to those in studies of intermittent dose IL-2 therapy. Also, negligible changes in the HIV viral load from baseline to final measurement were observed in both groups. A trend toward a reduced number of modifications of antiretroviral therapy was apparent in the IL-2 group when compared to control patients. CONCLUSION: Daily, low-dose subcutaneous IL-2 therapy in conjunction with HAART is safe and well tolerated and is effective in expanding lymphocyte cell types including NK cells and naive T cells in individuals who have <300 CD4+ T cells.

Randomized, double-blind, placebo-controlled trial of the immune modulator WF10 in patients with advanced AIDS.

A randomized, double-blind trial compared treatment with the immune modulator WF10 (ten patients) and placebo (nine patients) administered in cycles over 3 months among individuals with advanced AIDS. There were no notable clinical adverse events; changes in hematologic and chemistry values were comparable in the two groups. In both groups, median HIV-RNA PCR values remained stable. Immunologic variables showed a consistent tendency to increase in the WF10 group and to decrease in the control group, with significant differences between groups for median WBC, lymphocyte, CD19, and CD35 values. Ten infections occurred in the control group, four of which were Pneumocystis carinii pneumonia (PCP), and three in the WF10 group none of which was PCP. Five patients in the control group were hospitalized during the trial for a total of 53 days; no patients in the WF10 group were hospitalized. Over a subsequent 9-months follow-up, six patients from the control group and one from the WF10 group died. These results indicate that WF10 administration appears safe, may enhance immunologic function, and unlike other macrophage-activating cytokines does not increase HIV expression in this patient population. Further studies of WF10 in larger patient populations are warranted.

Clinical aspects of the interactions between human immunodeficiency virus and the hepatotropic viruses.

The hepatitis viruses A through D are prevalent among patients at risk for human immunodeficiency virus (HIV) infection. The courses of hepatitis B, C, and D are modified by HIV infection. With hepatitis B, increased carriage rates, increased viral replication, and milder liver injury are seen. The degree of HIV-induced immunosuppression does not correlate well with liver injury or amount of hepatitis B viral replication. With progression to AIDS, surface antibody titers can decline, resulting in reactivation of latent hepatitis B virus or reinfection with another subtype. hepatitis B virus may enhance progression to AIDS. Preliminary data suggest that HIV infection can prolong or increase hepatitis C or D viremia and decrease the accuracy of tests for hepatitis C. Interferon may have efficacy against hepatitis C but rarely against hepatitis B in patients who are coinfected with HIV. Zidovudine, ganciclovir, and foscarnet also may be active against these hepatotropic viruses.

Association of '(tropical) ataxic neuropathy' with HTLV-II.

Jamaican Neuropathy of the ataxic type (tropical ataxic neuropathy [TAN] and spastic type (tropical spastic paraparesis [TSP]) have been recognized for over a century in Jamaica. The recent association of TSP with HTLV-I (TSP/HAM) is now well established. We now present evidence for a possible association between a TAN-like illness with HTLV-II in four females aged 34-49. All presented with ataxic gait and all four have prominent mental changes. Three of the four also have minor motor deficits with urinary frequency and two have nocturnal leg cramps. All have serum antibody and all had PCR evidence of HTLV-II infection. Antibody to HTLV-II is present in CSF from two subjects. The distinctive picture of prominent ataxia and altered mental status in these subjects contrasts with a predominantly myelopathic picture seen in TSP/HAM.

Native valve endocarditis due to Pseudallescheria boydii in a patient with AIDS: case report and review.

A 53-year-old man with AIDS developed mitral valve endocarditis due to infection with the fungus Pseudallescheria boydii. A limited number of cases of prosthetic valve endocarditis caused by this organism have been described. We report a unique case of pseudallescheria infection of a native valve and describe this disease in a patient with AIDS.

Assessment of cardiac function in patients with the acquired immunodeficiency syndrome.

We have assessed right and left ventricular function by multigated radionuclide ventriculography in 12 consecutive patients with acquired immunodeficiency syndrome (AIDS) grouped according to the CDC classification system for HIV infection. Results were correlated with clinical, electrocardiographic and echocardiographic findings. Clinical examination and chest x-ray films showed no evidence of acute cardiac or pulmonary pathology. Five patients had evidence of ventricular dysfunction by radionuclide ventriculography along with significant ECG abnormalities. Three patients had abnormal ECG findings with normal ejection fractions. Echocardiography showed no evidence of significant valvulopathy or pericardial disease except for one patient with fibrinous strands associated with the pericardium. Decreased ejection fractions did not correlate with disease classification, risk group or survival. This study suggests that a major percentage of AIDS patients have some evidence of cardiac abnormalities. We conclude that abnormal ECG findings in an AIDS patient should alert the clinician to possible underlying ventricular dysfunction.

Antiviral activity of coumermycin: identification of resistant and sensitive retrovirus strains.

The effect of Coumermycin (CA1) on the replication of different ecotropic retroviruses was studied. Most strains showed reductions in infectivity of less than ten fold, while two strains demonstrated a marked sensitivity to the drug. The isolation of one resistant strain could suggest a specific CA1 antiviral activity.

Characterization of tumor cell lines from a spontaneous rat sarcoma expressing an endogenous retrovirus.

We have characterized various biologic, immunologic and growth properties of several cell lines established from a spontaneous rat sarcoma that was discovered more than 60 yr ago. The tumors consisted of mixed cell types with no detectable host cellular immune response. Cultures derived from single-cell clones of the parental cell line were non-invasive but highly tumorigenic even in adult rats. The cultured cells spontaneously released replication-competent endogenous rat type C virus which did not carry a transforming gene in its genome. Since normal cells from the same rat strain did not produce a retrovirus, it is possible that production of the endogenous retrovirus may have triggered specific cellular changes necessary for the oncogene expression and development of this tumor.

Coumermycin inhibition of murine retrovirus replication in cultured cells.

The effect of coumermycin A1 activity on the infection and replication of murine type C retroviruses was studied in vitro. The infectivity of five prototype ecotropic retroviruses was reduced by 50 to 94%, with viral titres decreased up to seven-fold. These values were substantiated by progeny production studies. Similar results were obtained with five strains of xenotropic retroviruses. Delayed inhibition of growth kinetics in mouse SC-1 cells was observed with 7.5 and 10 mg/l of coumermycin A1. This effect was markedly reduced after three cycles of freezing and thawing of the drug. Changes in the absorption spectra of coumermycin A1 were observed after eight cycles of freezing and thawing.

Host range differences among xenotropic type C retroviruses isolated from mouse kidney cell cultures.

By co-cultivation procedures, infectious xenotropic type C viruses have been recovered from kidney cells of several strains of mice. They have host-range patterns which place them into separate subgroups. In cells cultivated from one NZB kidney, two biologically different xenotropic type C retroviruses were found. One, X-NZB/K-1, infects and replicates well in human and mink fibroblast cells but does not induce foci in mink S + L - cells with good efficiency. The other, X-NZB/K-2, infects and replicates well in mink but not human fibroblast cells, and induces foci readily in mink S + L - cells. Cross-infection studies indicate that these viruses, classified as xenotropic by host range and envelope properties, are genetically stable.

Sensitive micro in situ fluorescent focus assay for detection of murine xenotropic retroviruses.

A sensitive micro in situ fluorescent focus assay (mISFA), which utilizes cell monolayers fixed on a plastic surface, was developed for the detection of NZB xenotropic type C retroviruses grown in mammalian cell lines. The mISFA technique is an easier, more rapid and less expensive assay than other biological tests used to detect these viruses; it gives a more precise viral titer and is slightly more sensitive. This technique allows extension of host-range investigations to include any growing cell cultures and is applicable to various virus-host cell systems.