Correlations between long inverted repeat (LIR) features, deletion size and distance from breakpoint in human gross gene deletions

Long inverted repeats (LIRs) have been shown to induce genomic deletions in yeast. In this study, LIRs were investigated within ±10 kb spanning each breakpoint from 109 human gross deletions, using Inverted Repeat Finder (IRF) software. LIR number was significantly higher at the breakpoint regions, than in control segments (P < 0.001). In addition, it was found that strong correlation between 5′ and 3′ LIR numbers, suggesting contribution to DNA sequence evolution (r = 0.85, P < 0.001). 138 LIR features at ±3 kb breakpoints in 89 (81%) of 109 gross deletions were evaluated. Significant correlations were found between distance from breakpoint and loop length (r = −0.18, P < 0.05) and stem length (r = −0.18, P < 0.05), suggesting DNA strands are potentially broken in locations closer to bigger LIRs. In addition, bigger loops cause larger deletions (r = 0.19, P < 0.05). Moreover, loop length (r = 0.29, P < 0.02) and identity between stem copies (r = 0.30, P < 0.05) of 3′ LIRs were more important in larger deletions. Consequently, DNA breaks may form via LIR-induced cruciform structure during replication. DNA ends may be later repaired by non-homologous end-joining (NHEJ), with following deletion

Integrase strand transfer inhibitors and neuropsychiatric adverse events in a large prospective cohort

To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs)

Reaching the Second and Third Joint United Nations Programme on Human Immunodeficiency Virus (HIV)/AIDS 90-90-90 Targets Is Accompanied by a Dramatic Reduction in Primary HIV Infection and in Recent HIV Infections in a Large French Nationwide HIV Cohort

International audienceAbstract Background In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. Methods To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. Results During the study period, 61 822 patients were followed in the Dat’AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. The median delay between HIV diagnosis and cART initiation decreased from 9.07 (interquartile range [IQR], 1.39–33.47) months in 2007 to 0.77 (IQR, 0.37–1.60) months in 2017. A decrease in PHI (−35.1%) and PRHI (−25.4%) was observed starting in 2013. The breakpoints for PHI and PRHI were 2012.6 (95% confidence interval [CI], 2010.8–2014.4) and 2013.1 (95% CI, 2011.3–2014.8), respectively. Conclusions Our findings show that the achievements of 2 public health targets in France and the early initiation of cART were accompanied by a reduction of about one-third in PHI and PRHI between 2013 and 2017. Clinical Trials Registration NCT02898987

No barrier to care, yet disparities in the HIV care continuum in France: a nationwide population study

International audienceAbstract Objectives Even in an ‘optimal’ health system, patients’ characteristics may have an impact on their care. We investigated whether age, gender and place of birth have an impact in the HIV care continuum in France, a country with a universal free healthcare system. Methods We estimated differences in the 5 year restricted mean percentage of person-time spent (i) in care, (ii) receiving ART and (iii) on ART and virally suppressed among 2432 (30.2%) women, 3925 MSM (48.7%) and 1709 men who have sex with women (MSW; 21.2%) entering care in the Dat’AIDS French prospective cohort between 1 January 2013 and 31 December 2017. Trial registration: Clinicaltrials.gov reference NCT02898987. Results Men and women spent 85.6% and 82.8% of person-time on ART and 69.9% and 65% suppressed, respectively. MSM, MSW and women spent 86.9%, 82.6% and 82.8% of person-time on ART and 72.5%, 63.7% and 65% suppressed, respectively. Patients born in France (47%) and patients born abroad spent 87.9% and 81.9% of person-time on ART and 74.6% and 62.9% suppressed, respectively. Young men born abroad were found to spend the smallest person-time with non-detectable viral load (53% for MSW and 58.1% for MSM). Conclusions Despite free access to care and universal ART in France, disparities remain in the HIV continuum care across age, country of birth and way of HIV acquisition. Clinical and public health interventions targeting specific patients’ conditions are needed