QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in Tuberculosis Contact Tracing: A Noninferiority Clinical Trial.

Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. Results: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials Registration: NCT01223534.

[Primary care doctors attitudes and practices in the diagnosis of HIV infection]. / Actitudes y prácticas de los médicos de atención primaria ante el diagnóstico de la infección por virus de la inmunodeficiencia humana.

OBJECTIVE: To explore the attitudes and practices of Primary Health Care professionals in the diagnosis of HIV infection according to current protocols and the degree of acceptance of simplified HIV testing (without a separate written consent and without asking about risk practices). MATERIAL AND METHODS: An observational cross-sectional descriptive study conducted in Primary Care Centres of the Madrid Public Health Service. Data were collected by telephone surveys during 2009. RESULTS: A total of 210 doctors were interviewed. Twenty one percent were already performing simplified HIV testing (and 28.6% expressed a favourable attitude towards the new recommendations). The majority (71.4% did not use a separate written consent for HIV testing, and 42% did not report any communication difficulties. Most of them considered that comparing HIV with other similar ways of transmission infections, making HIV testing exceptual may lead to stigma. Lack of time was not a problem for 75.2%, and 97.1% considered they had an essential role in controlling the HIV epidemic. CONCLUSIONS: The acceptance of simplified HIV testing is high and is already being performed by 1 out of 5 Primary Care Doctors in the Madrid Public Health Service.

Overcoming resistance: virologic response to a salvage regimen with the combination of ritonavir plus indinavir.

PURPOSE: To explore the possibility of overcoming resistance to protease inhibitors (PIs) and to determine the resistance cutoff values that continue to predict treatment failure with a dual PI regimen. METHOD: We performed a prospective study of 53 patients who had failed in several PIs and who were included in a ritonavir (RTV) plus indinavir (IDV) salvage regimen. Median HIV RNA level decrease was evaluated according to resistance assays and indinavir trough levels. RESULTS: Eighty-seven percent of patients had previously failed on an IDV-containing regimen. Overall, median HIV RNA decrease was -1.25 log(10) copies/mL after 3 months on therapy. A significant blunted virologic response was observed only in isolates with more than 12 substitutions including the V82A (-0.75 vs. -1.3 log(10) copies/mL; p =.04), or in isolates with more than 30 fold-increase in the IC(50) (-0.43 vs. -1.2 log(10) copies/mL). Higher drug levels were observed in patients with resistant isolates who achieved an HIV RNA decrease greater than 1 log (1742 vs. 1100 ng/mL). CONCLUSION: Our preliminary data suggest the possibility of overcoming resistance with the combination of RTV plus IDV. They also suggest the need for establishing new resistance cutoff values when using PIs in combination.