Predictors of incomplete viral response and virologic failure in patients with acute and early HIV infection. Results of Italian Network of ACuTe HIV InfectiON (INACTION) cohort.

OBJECTIVES: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). METHODS: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. RESULTS: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. CONCLUSIONS: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.

The changing face of the HIV epidemic in Northern Sardinia: increased diagnoses among pregnant women.

BACKGROUND: Combination antiretroviral therapy has reduced both HIV/AIDS related morbidity and mortality. However, while the number of new AIDS diagnosis progressively declined in Europe from 1997 to 2004, new HIV infection diagnoses showed an increase since 1998. Unfortunately, there is no national HIV reporting system in Italy, and no information is available from the South and the islands. METHODS: Data on new HIV infections diagnosed in northern Sardinia between 1997 and 2004 were retrospectively collected. Thus, two four years periods (1997-2000 vs 2001-2004) were compared in order to assess changes in the characteristics of newly diagnosed individuals. RESULTS: Overall, 156 new HIV infection diagnoses occurred during the study period, 87 (55.8%) in males and 69 (44.2%) in females. The incidence rate per 100,000 inhabitants showed a progressive decline from 1997 (5.9) to 2001 (3.3), followed by a rapid increase in 2002 (5.0) and a new decline in 2004 (3.5). Median age progressively increased over the study period, from 33 years in 1997 to 38 in 2004. Males (55.8%) were more frequently affected than females (44.2%), who showed a trend toward a slight but progressive proportional increase. With regard to the exposure category, 95 (60.9%) individuals were heterosexual contacts, 38 (24.4%) injection drug users (IDU), 17 (10.9%) homosexual men, and 6 (3.8%) not determined (ND). There was a proportional increase for homosexual men (+7.5%) and heterosexual contacts (-7.9%), while IDU showed a slight decrease ( 2.7%). Heterosexual intercourse was the main exposure category both for women (78%) and men (47.1%), but man-to-man sex increased in the last study period. IDU still accounted for 20.3% and 27.5% of the cases among women and men, respectively. An increase in the proportion of new diagnoses in pregnant women, from 8.6% to 20.6%, was also observed. All pregnant women diagnosed in the first four years period were Italian, whereas 4 of the 7 (57.1%) women diagnosed thereafter were foreigner. Finally, the proportion of new HIV diagnoses in foreigners showed a marked increase, from 2.4% to 17.6%; of them 71.4% originated from sub-Saharan Africa. CONCLUSIONS: Our results suggest that the HIV epidemic is far from being controlled in our Region. Prevention campaigns targeted to homosexual men, women and migrants are needed. Non-HIV specialists, such as gynaecologists and obstetricians, as well as general practitioners, should routinely offer HIV testing to pregnant women.

Leucine-enkephalin increases the level of inositol (1,4,5) triphosphate and releases calcium from an intracellular pool in rat ventricular cardiac myocytes.

In rat ventricular cardiomyocytes loaded with the fluorescent Ca2+ indicator Indo-1/AM, the delta opioid receptor agonist Leu-Enk caused Cai oscillations and abolished the caffeine-induced Cai transient. During superfusion of cardiomyocytes with the specific opioid antagonist naloxone, Cai is not affected by Leu-Enk and the caffeine-triggered Cai transient is preserved. In parallel experiments with cardiac myocytes, the delta opioid agonist increased the intracellular level of Ins (1,4,5) P3 by about 4 times above the control value. Such an effect was completely antagonized by naloxone. Thus, Leu-Enk induces depletion of Ca2+ from the SR by a receptor-mediated mechanism which appears to involve an increase in the intracellular level of Ins (1,4,5) P3.