Pretreatment HIV-1 drug resistance in Argentina: results from a surveillance study performed according to WHO-proposed new methodology in 2014-15.

BACKGROUND: In Argentina, current national guidelines recommend starting with NNRTI-based regimens. Recently, there have been some local reports regarding concerning levels of NNRTI-transmitted resistance, but surveillance has never been carried out at a national level. OBJECTIVES: To determine the prevalence of HIV drug resistance in people starting ART in Argentina using a WHO-proposed methodology. METHODS: This was a cross-sectional, nationally representative study. Twenty-five antiretroviral-dispensing sites throughout the country were randomly chosen to enrol at least 330 persons starting ART, to generate a point prevalence estimate of resistance-associated mutations (RAMs) with a 5% CI (for the total population and for those without antiretroviral exposure). All consecutive patients older than 18 years starting or restarting ART in the chosen clinics were eligible. Samples were processed with Trugene and analysed using the Stanford algorithm. RESULTS: Between August 2014 and March 2015, we obtained 330 samples from people starting ART. The mean ±â€ŠSD age was 35 ±â€Š11 years, 63.4% were male, 16.6% had prior antiretroviral exposure and the median (IQR) CD4 count was 275 cells/mm3 (106-461). The prevalence of RAMs found was 14% (±4%) for the whole population (3% NRTI-RAMs; 11% NNRTI-RAMs and 2% PI-RAMs) and 13% (±4%) for those without prior antiretroviral exposure (3%, 10% and 2%, respectively). The most common mutation was K103N. CONCLUSIONS: This surveillance study showed concerning levels of HIV drug resistance in Argentina, especially to NNRTIs. Due to this finding, Argentina's Ministry of Health guidelines will change, recommending performing a resistance test for everyone before starting ART. If this is taken up properly, it also might function as a continuing surveillance tool.

Characterization and functional significance of glucocorticoid receptors in patients with major depression: modulation by antidepressant treatment.

Hyperactivity of the hypothalamic pituitary adrenal (HPA) axis in patients with major depression is one of the most consistent findings in biological psychiatry. Experimental data support the idea that glucocorticoid-mediated feedback via glucocorticoid receptors (GR) is impaired in major depression. The aim of the present work was to assess the putative changes in GR density of peripheral blood mononuclear cells (PBMCs) in a group of patients with major depression and to determine modulation of these GR sites by antidepressant treatment. In addition, susceptibility of PBMCs to glucocorticoid effects was also studied using a functional end-point analysis in vitro, such as cortisol inhibition of mitogen-induced lymphocyte proliferation. Cortisol levels were also measured before and after dexamethasone suppression test (DST). The results showed a decrease in GR density in depressed patients compared with healthy subjects, mainly in those patients that showed basal cortisol levels in the upper normal range and were refractory to DST. Regarding the functional significance of this variation, two representative groups emerged from our study: a) free-medication patients with GR function comparable to healthy controls, and b) patients showing diminished GR activity. These results suggest a lack of relationship between GR density and cortisol-induced inhibition of lymphocyte proliferation. Patients treated with different antidepressant drugs showed a marked increase in the number of GR sites per cell compared to non-treated. Interestingly, this increase was even higher than in normal subjects. Hence, restoration of GR density after an efficient antidepressant treatment could be an index of an effective modulatory action of drugs on GR expression and highlights the possibility that GR levels might be used as markers of a successful treatment.