Utility of QuantiFERON-TB Gold in-tube testing for latent TB infection in HIV-infected individuals.

SETTING: Urban inner city human immunodeficiency virus (HIV) clinic. OBJECTIVE: To evaluate tuberculin skin testing (TST) and QuantiFERON-TB Gold (QFT-G) testing in an HIV-infected population relative to the presence of risk factors for latent tuberculosis infection (LTBI). DESIGN: Cross-sectional analysis of the response of a whole blood gamma interferon release assay to early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) antigens and TST relative to known risk factors for LTBI. RESULTS: Of 207 subjects enrolled, four were excluded due to missing data and three specimens yielded discordant results. Ten specimens were indeterminate due to inadequate response to mitogen. All indeterminate results occurred in subjects with CD(4) counts <200 cells/mm(3). Eleven QFT-G results and 13 TST results were positive. The concordance between TST and QFT-G was poor (kappa 0.38). QFT-G results were more likely than TST to be associated with risk factors for LTBI. CONCLUSIONS: QFT-G, but not TST, showed a statistically significant association between the number of risk factors for LTBI and a positive result (OR 1.6). QFT-G testing may be more useful than TST in individuals with HIV infection.

Infectious disease. Update on treatment of pneumonia, influenza, and urinary tract infections.

Older persons are at increased risk for infection because of decreased physiologic reserves, acute and chronic comorbidities, time spent in hospitals or nursing homes, and high exposure to invasive procedures in those settings. Management of infection in older persons is complicated by several factors, including microbial resistance and the infrequency or absence of common infection signs and symptoms. Among the most common infections in older populations are community-acquired pneumonia, influenza, and urinary tract infection. Vigilance, early diagnosis, and strategic use of antibacterial or antiviral agents are key to effective patient management.

Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease.

BACKGROUND: Mortality and morbidity related to AIDS have decreased among HIV-infected patients taking highly active anti-retroviral therapy (HAART), but previous studies may have been confounded by other changes in treatment. OBJECTIVE: To assess the benefit of HAART in patients with advanced AIDS and anemia. DESIGN: Prospective, multicenter cohort study. SETTING: The Viral Activation Transfusion Study (VATS), with enrollment from August 1995 through July 1998 and follow-up through June 1999. PATIENTS: 528 HIV-infected patients with cytomegalovirus (CMV) seropositivity or disease who were receiving a first red blood cell transfusion for anemia. MEASUREMENTS: In a person-year analysis of follow-up before and after initiation of HAART, Poisson regression was used to calculate crude rate ratios and rate ratios adjusted for CD4 count, HIV RNA level, calendar period, time on study, sex, ethnicity, and injection drug use. RESULTS: At baseline, patients had a median CD4(+) lymphocyte count of 0.015 x 10(9) cell/L, median plasma HIV RNA level of 4.8 log(10) copies/mL, and median hemoglobin concentration of 73 g/L. Use of HAART increased from 1% of active patients in January 1996 to 79% of active patients in January 1999. The crude death rate was 0.24 event/person-year among patients taking HAART and 0.88 event/person-year among those not taking HAART (rate ratio, 0.26; adjusted rate ratio, 0.38; P < 0.001 for both comparisons). Rates of non-CMV disease were 0.15 event/ person-year after HAART and 0.45 event/person-year before HAART (crude rate ratio, 0.34 [ P < 0.001]; adjusted rate ratio, 0.66 [ P < 0.05]). Rates of CMV disease were 0.10 event/person-year after HAART and 0.25 before HAART (crude rate ratio, 0.42 [ P < 0.01]; adjusted rate ratio, 1.01 [ P > 0.2]). Results were similar in patients with baseline CD4(+) lymphocyte counts less than 0.010 x 10(9) cells/L. CONCLUSIONS: The data support an independent reduction in mortality and opportunistic events attributable to HAART, even in patients with very advanced HIV disease. However, patients with CMV infection or disease may not have a reduction in new CMV events due to HAART.

Qualitative and quantitative PCR measures of cytomegalovirus in patients with advanced HIV infection who require transfusions.

The Viral Activation Transfusion Study (VATS) was a randomized trial that compared leukocyte-reduced transfusions with unfiltered red blood cell transfusions in HIV and cytomegalovirus (CMV) antibody-positive patients with anemia who were undergoing their first blood transfusion. The relations of the baseline qualitative and quantitative polymerase chain reaction (PCR) measures of plasma CMV viremia, HIV RNA, CD4(+) cell counts, and quality of life in these study subjects were examined. The 511 study subjects had a median CD4(+) cell count equal to 15 cells/mm3, and 110 (21.5%) had CMV viremia by qualitative assay. In multivariate models, frequency of positive qualitative CMV increased with decreasing CD4(+) cell counts (p =.04 trend), higher HIV RNA (p <.001), and a history of CMV disease (p <.001). Quantitative CMV PCR were performed on the 110 qualitative assay-positive study subjects. Median CMV viral load was 1780 copies/ml. In multivariate regression models, lower CD4(+) cell count (p =.03), and a history of CMV disease (p <.001) correlated with the level of CMV load. HIV RNA load and CMV load were not correlated. A lower Karnofsky score was associated with both the presence and quantity of CMV DNA.

Determinants of antimicrobial prophylaxis use and treatment for wasting among patients with advanced human immunodeficiency virus disease in the United States, 1995-1998.

Despite US Public Health Service (USPHS) recommendations for antimicrobial prophylaxis for patients with advanced human immunodeficiency virus (HIV) disease, the proportion of patients who receive prophylaxis is not known. We measured the prevalence of antimicrobial prophylaxis use, and treatment for HIV wasting at baseline among 531 patients with advanced HIV disease enrolled in a multicenter randomized trial of red blood cell transfusion. Use of antimicrobial prophylaxis and treatment for wasting in the 30 days before enrollment was ascertained in patients eligible for primary prophylaxis, secondary prophylaxis, or both, according to USPHS guidelines. There was high utilization of primary and secondary Pneumocystis carinii pneumonia prophylaxis, variability in primary Mycobacterium avium complex prophylaxis by center, and low use of primary cytomegalovirus prophylaxis. Treatment of wasting was more common in white than nonwhite patients and in patients with HIV disease who lived in the region west of the Mississippi River of the United States versus those whose lived in the eastern region.

Circulating Borrelia burgdorferi in patients with acute Lyme disease: results of blood cultures and serum DNA analysis.

To determine the usefulness of blood culture and polymerase chain reaction (PCR) analysis in detecting circulating Borrelia burgdorferi or its DNA, blood and serum from untreated patients with acute Lyme disease were examined. None of the cultures of blood or serum from the 7 patients tested demonstrated spirochetes. Similarly, all patient serum samples, assayed in two laboratories, were negative for B. burgdorferi DNA using PCR amplification. These results suggest that in patients with acute Lyme disease, spirochetes, spirochete DNA, or both circulate early, only intermittently, or at low levels and that neither culture nor PCR testing of blood or serum, as currently done, appears likely to prove generally useful in the diagnosis of Lyme disease.

Differential inhibition of human T-lymphocyte activation by maleimide probes.

Cellular thiols are known to be involved in lymphocyte activation, differentiation, and growth. In theory, alkylation of selective cellular thiols could be used to regulate specific processes in the activation sequence by inactivating particular enzymes or structural proteins, although to date specific alkylating probes have not been reported. N-Ethylmaleimide (NEM) is a lipophilic sulfhydryl-alkylating agent that is known to block the in vitro proliferative response of T lymphocytes. NEM (10 microM) was found to be fully inhibitory in PHA, Con A, and MLC assays only when added prior to or simultaneously with the mitogens or allogeneic cells; the addition of NEM only 15 sec after stimulating the cells with PHA resulted in a loss of greater than 50% of the inhibitory activity. The addition of 50 microM 2-ME 10 min after treating the cells with NEM failed to block the inhibitory effect. NEM (10-20 microM) had no adverse effect on lymphocyte viability, but completely blocked lymphocyte agglutination in response to mitogens or allogeneic cells. The lymphocytes overcame the inhibitory effects of NEM after 48 hr in both the PHA and MLC experiments. Resumption of the proliferative response was associated with the onset of agglutination in the PHA assay. In experiments using various analogs of NEM, we noted that the presence of a nonpolar N-linked side group was necessary for inhibitory activity. Pretreatment of PBMC with NEM decreased the total cellular thiols by 50% and blocked proliferation by 99%, whereas N-hydroxymaleimide decreased the total cellular thiols by 38% but had no effect on the proliferative response. The additional 12% of the cellular thiols that react with NEM, but not NHM, account for the inhibitory effect of NEM on lymphocyte proliferation. These findings suggest that selective cellular thiols are critical for T-cell activation.