Incidences and risk factors of first-line HAART discontinuation: a limitation to the success of the "seek, test, treat, and retain" strategy?

To evaluate the incidence and risk factors of first-highly active antiretroviral therapy (HAART) modifications/interruptions and their causes in a cohort of newly-treated patients by using a competing risk model. In nine centers of the French cohort Dat'AIDS, in 1 year and 2 years of censorship, a competing risk analysis was implemented in HIV1 patients aged 18 years or older first-treated between September 2002 and March 2012. In 4669 patients, 3628 modifications (77.7%) were observed (median: 13.5 months). Cumulative incidence in 1 year: 46.8% [45.4-48.3]; in 2 years: 65.3% [63.8-66.8]. Intolerance (n = 1167; 32.3%): in 1 year, except first-treated from 2002 to 2005, modifications were not different: 2002-2003 (24.6%) 2004-2005 (26.1%), 2006-2007 (19.4%), 2008-2009 (18.8%) and 2010-2011 (15.7%). Women, AIDS patients, and those aged 50 years and older had an excess risk. Therapeutic simplification (n = 1037; 28.6%): in 1 year, except first-treated from 2002 to 2003, modifications were not different: 2002-2003 (9.0%), 2004-2005 (16.0%), 2006-2007 (11.0%), 2008-2009 (15.7%) and 2010-2011 (10.0%). Conversely to injecting-drug-users and AIDS patients, women and first-treated with non-nucleosides had an excess risk. Therapeutic failure (n = 189; 5.2%): contrary to first-treated between 2002 and 2003 or 2008 and 2009, in 1 year as in 2 years, modifications were not different. In 1 year, 1.9% for 2004-2005, 1.6% for 2006-2007 and 1.2% for 2010-2011. Maximum viral load ≥5.0 log10 copies/ml and CD4 <200 cells/mm(3) had a high probability. The study of first-HAART modifications suggests that in 1-year follow-up, intolerance incidence in the recent calendar year is still as frequent as the previous period which may constitute a limitation to the success of the seek, test, treat, and retain.

Frequency, determinants and consequences of delayed access to care for HIV infection in France.

BACKGROUND AND OBJECTIVES: We analysed the frequency and predictors of delayed access to care (DAC) for HIV infection, and its influence on survival. METHODS: We studied predictors of DAC among 18,721 patients enrolled between 1997 and 2002 in the French Hospital Database on HIV (FHDH), DAC being defined by a CD4* T-cell count below 200 copies/mm3 and/or AIDS at FHDH enrollment. The association of DAC with the initiation of combined antiretroviral therapy (cART) and of DAC with survival were analysed with Cox multivariable models. RESULTS: The overall prevalence of DAC was 35.7%. Compared with patients under 30 years of age, patients over 60 were 3.5 times more likely to have DAC (P < 10(-4)). Compared with non-migrant women, odds ratios (OR) of DAC were higher among migrant women (1.5), non-migrant men (1.6) and migrant men (1.9; all P < 10(-4)). Compared with men who have sex with men, other transmission groups had an estimated OR for DAC of 1.6 (P < 10(-4)). DAC was more frequent among patients with a recent diagnosis of HIV infection [OR = 1.3, 95% confidence intervals (CI) = (1.2;1.4)]. Patients with DAC received cART earlier than other patients [hazard ratio (HR) = 2.2, 95% CI = (2.1;2.3)]. The DAC/mortality HR was 13.9 in the first 6 months after enrollment in the FHDH, and remained significantly higher than 1 during the subsequent 4 years. CONCLUSION: DAC is common in France and was associated with a higher mortality, despite early initiation of cART. Earlier access to care and specific clinical management of patients with DAC should be considered.

COPD in HIV-Infected Patients: CD4 Cell Count Highly Correlated.

BACKGROUND: COPD is a frequent and significant cause of respiratory morbidity in HIV-infected patients despite the control of HIV. We aimed to analyze the factors correlated with COPD in this population to evaluate the existence of specific indicators of vulnerability in this population. METHODS AND FINDINGS: 623 HIV-infected outpatients were enrolled during one year. This population was characterised by a dedicated questionnaire and electronic patient records. COPD screening was performed according to recommended spirometric criteria. The prevalence of COPD was 9.0%. Age and smoking were independently correlated with COPD (OR, 1.61 per 10 years increase, P = 0.007; OR, 1.28 per 10 pack-year increase, P = 0.003, respectively). Body mass index (BMI) and CD4 cell-count were independently and negatively correlated with COPD (OR, 0.78, P < 0.001; 0R, 0.77 per 100 cell/mm3 increase, P < 0.001, respectively). Among COPD patients, 77% did not know their diagnosis. Five COPD-patients never smoked and 44.2% did not have any respiratory symptoms and so were not eligible to perform a spirometry according to the guidelines. CONCLUSIONS: In addition to known risk factors, immune defect through CD4 cell count was independently and strongly correlated with COPD. COPD is largely underdiagnosed and thus unmanaged. However, early management and urgent smoking cessation are essential to improve prognosis. Clinicians' awareness on the particular vulnerability for COPD in HIV-infected patients is crucial. Moreover, indications to perform conventional spirometry to diagnose COPD may include more parameters than tobacco-smoking and respiratory complaints with a particular concern toward patients with a profound CD4 cell count defect.

Virological response and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus coinfection.

AIM: To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients in a real life setting. METHODS: Patients with HCV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin (PegIFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database (Nadis(®)). Liver fibrosis was measured by elastometry (Fibroscan(®)) with the following cut-off values: F0-F1: < 7.1 kPa, F2: 7.1-9.5 kPa, F3: 9.5-14.5 kPa, F4: ≥ 14.5 kPa. The proportion of patients with sustained virological response (SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described. RESULTS: Forty-one patients were included: 13 (31.7%) patients were HCV-treatment naïve, 22 (53.7%) had advanced liver fibrosis or cirrhosis (Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them (83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia (88%) and rash (25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation could predict resistance to HCV protease inhibitor-based treatment. CONCLUSION: Telaprevir and boceprevir retain their place among potential treatment strategies in HIV-HCV coinfected patients including those with advanced compensated liver disease and who failed previous PegIFN/RBV therapy.

Apoptosis of naive CD4+ T-cells from HIV-infected patients with poor immune response to HAART is enhanced in vitro by steroid.

OBJECTIVE: Because the absence of immune restoration in HIV-infected patients efficiently treated by highly active antiretroviral therapy (HAART) may be due to excessive immune activation, we prospectively studied the effect of hydrocortisone on T-cell apoptosis in a cohort of patients with satisfactory virologic response. METHODS: Apoptosis of T-cell subsets including naïve CD45RA(+)CD4+ T-cells was determined at baseline and at months 1 and 3 after initiation of HAART. A satisfactory immune response was defined as an increase >100/microL CD4+ T-cells at month 3 compared to baseline. RESULTS: Twenty out of 63 patients showed undetectable viral load at month 3, among whom eight exhibited a satisfactory immune response. Down-regulation spontaneous CD4+T-cell apoptosis was significant in the group of patients with a satisfactory immune response compared to the other patients. However, hydrocortisone up-regulated apoptosis of naïve CD4+ CD45RA+ T-cells, specifically in group of patients with poor immune response, whatever the time point considered: percentage of apoptotic CD4 T-cells was 16+/-16% without hydrocortisone and 22+/-22% with hydrocortisone at month 1, and respectively, 10+/-9 and 17+/-15% at month 3 (P < 0.05) Hydrocortisone had no impact on CD8+ T-cell apoptosis, whatever the considered group. CONCLUSION: Our results suggest to not use steroid therapy as adjuvant immunotherapy in patients with less than optimal immunologic response to HAART.