HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays.

BACKGROUND: Because of high intersubtype HIV-1 genetic variability, it has been shown that subtype-specific patterns of resistance to antiretroviral drugs exist. We wished to ascertain whether this might be true for integrase inhibitors. METHODS: We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors. This was performed biochemically using a microtiter plate system. RESULTS: Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two integrase inhibitors, raltegravir and elvitegravir, than were subtype B recombinant integrase containing the same mutations. CONCLUSION: Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance. It is possible that different viral subtypes may favor different mutational pathways, potentially leading to varying levels of drug resistance among different subtypes.

Validation of two blood pressure measurement devices according to the European Society of Hypertension International Protocol: the citizen CH-463E and the citizen CH-461C.

OBJECTIVE: The validation of two new oscillometric blood pressure (BP) measurement devices according to the International Protocol (European Society of Hypertension). METHODS: Two trained observers measured BP in 33 patients with nine sequential same-arm measurements each, whereby five measurements with the mercury standard device alternated with four measurements with each of the test devices per patient. The resulting differences between the BP value read by the devices and the BP value obtained by the two observers were used for evaluation. RESULTS: The Citizen CH-463E and the Citizen CH-461C devices passed the International Protocol requirements. CONCLUSION: Both devices can be recommended for clinical use in patients with upper-arm circumferences matching the cuffs used in the test.

Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes.

BACKGROUND: Integrase inhibitors are currently being incorporated into highly active antiretroviral therapy (HAART). Due to high HIV variability, integrase inhibitor efficacy must be evaluated against a range of integrase enzymes from different subtypes. METHODS: This study compares the enzymatic activities of HIV-1 integrase from subtypes B and C as well as susceptibility to various integrase inhibitors in vitro. The catalytic activities of both enzymes were analyzed in regard to each of 3' processing and strand transfer activities both in the presence and absence of the integrase inhibitors raltegravir (RAL), elvitegravir (EVG), and MK-2048. RESULTS: Our results show that integrase function is similar with enzymes of either subtype and that the various integrase strand transfer inhibitors (INSTIs) that were employed possessed similar inhibitory activity against both enzymes. CONCLUSION: This suggests that the use of integrase inhibitors against HIV-1 subtype C will result in comparable outcomes to those obtained against subtype B infections.

Trial of validation of two devices for self-measurement of blood pressure according to the European Society of Hypertension International Protocol: the Citizen CH-432B and the Citizen CH-656C.

OBJECTIVE: Two devices for self-measurement of blood pressure, one at the upper arm (Citizen CH-432B) and one at the wrist (Citizen CH-656C), were evaluated according to the International Protocol of the European Society of Hypertension. DESIGN: The International Protocol is divided into two phases: the first phase is performed on 15 selected participants with five participants in three different blood pressure ranges. If the devices passed this phase, 18 additional participants selected on the basis of the same criteria as in phase 1 were included. METHODS: Two skilled observers performed the following blood pressure measurements: five measurements were performed with the mercury standard alternating with four measurements with each of the test devices per participant. The first measurement result from each device instrument was not included in the analysis. The difference between the blood pressure value given by the devices and that obtained by the two observers (mean of the two observers) was calculated for each pair of measurements and classified into three categories (within 5, 10 and 15 mmHg). The results were compared to the pass criteria established by the European Society of Hypertension. Afterwards the number of measurement differences falling within 5 mmHg was determined for every person. At least 22 of the 33 participants should have two of their three comparisons within 5 mmHg and there should be a maximum of three participants without a measurement difference within the 5 mmHg range. RESULTS: Both tested devices passed the first phase of the validation process by exceeding the required number of comparisons falling within the 5, 10 and 15 mmHg error zones. Even the second phase confirmed the validation criteria with average differences between the device and the mercury sphygmomanometer of 0.7+/-4.4 and -3.6+/-4.0 mmHg for systolic blood pressure and diastolic blood pressure, respectively, for the Citizen CH-432B device and -0.7+/-6.0 and -1.2+/-4.5 mmHg for the Citizen CH-656C device. Phase 2 contains furthermore an individual analysis of the 33 participants, the requirements of which were also fulfilled by both devices. CONCLUSION: The Citizen CH-432B and the Citizen CH-656C devices pass the validation recommendations of the International Protocol. They can be recommended for clinical use.