Soluble biomarkers of immune activation and inflammation in HIV infection: impact of 2 years of effective first-line combination antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess the impact of rapid and sustained viral control produced by combination antiretroviral therapy (cART) on HIV-associated immune activation and inflammation. METHODS: In this longitudinal observational study, we examined changes in interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG) and soluble CD14 (sCD14) levels during 2 years of effective first-line cART. Biomarker levels before and after cART were compared with those observed in healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels were defined with respect to values for healthy subject (mean + 2 standard deviations). Factors associated with persistently elevated biomarker levels after 2 years of cART were identified by logistic regression. RESULTS: We included in the study 139 patients with a median HIV-1 RNA level of 4.8 log10 HIV-1 RNA copies/mL and a median CD4 cell count of 294 cells/µL at cART initiation [day 0 (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P < 0.05). After 2 years of cART, IL-6, IP-10 and MIG levels fell significantly, by a median of 0.54, 420 and 1107 pg/mL, respectively (all P < 0.001), and were no longer elevated in > 75% of patients. In contrast, sCD14 levels did not change significantly (0.18 × 10(6) pg/mL; P = 0.102) and remained elevated. Older age was associated with elevated levels of IP-10 [odds ratio (OR) 1.60 per 10 years older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years of cART. CONCLUSIONS: The rapid and sustained viral suppression produced by first-line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP-10 and MIG tended to persist in older patients.

Effect of CRESTAR on estrus synchronization and the relationship between fecal and plasma concentrations of progestagens in buffalo cows.

In buffaloes estrus synchronization provides an opportunity for enhanced use of AI; however, changes in hormone secretion during synchronization are poorly understood. The aim of this investigation was to determine if the concentration of progesterone metabolites in feces would correlate with the concentration of progesterone in blood and thus, could be used for noninvasive monitoring of the reproductive status in buffalo cows. Additionally, the influence of a norgestomet-estradiol treatment (CRESTAR-ear implant) was investigated. According to the clinical examination and the progesterone profile in blood samples during the three wks before the treatment, the 17 animals were allotted to 3 groups: 1) CL = presence of corpus luteum throughout the period of 3 wks before the treatment (n = 8); 2) CY = cyclic, corpus luteum present for less than 3 wks (n = 6); and 3) AE = anestrous, with inactive ovaries (n = 3). In the first group, 4 animals started an estrous cycle after implant withdrawal and conceived after natural mating. In the second group one of the cyclic cows showed estrus two d after implant withdrawal, the other 3 had a delayed estrus (12 to 16 d). The two cows which had had inactive ovaries at the beginning but were cyclic before the treatment started, remained cyclic after implant withdrawal but did not become pregnant. The 3 anestrous cows of the third group remained anestrous after the treatment. The progesterone concentration in blood clearly correlated with the concentration of the metabolites in feces. Therefore, this noninvasive method is a valuable tool for determining the luteal status, and such information may be useful for developing estrus synchronization regimens in buffalo cows.