Search

Background Both immediate and deferred switching from a ritonavir-boosted protease inhibitor (PI/r)–based regimen to a dolutegravir (DTG)–based regimen may improve lipid profile. Methods European Network for AIDS Treatment 022 Study (NEAT022) is a European, open-label, randomized trial. Human immunodeficiency virus (HIV)–infected adults aged ≥50 years or with a Framingham score ≥10% were eligible if HIV RNA was <50 copies/mL. Patients were randomized to switch from PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D). Week 96 endpoints were proportion of patients with HIV RNA <50 copies/mL, percentage change of lipid fractions, and adverse events (AEs). Results Four hundred fifteen patients were randomized: 205 to DTG-I and 210 DTG-D. The primary objective of noninferiority at week 48 was met. At week 96, treatment success rate was 92.2% in the DTG-I arm and 87% in the DTG-D arm (difference, 5.2% [95% confidence interval, –.6% to 11%]). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AEs or treatment-modifying AEs. Total cholesterol and other lipid fractions (except high-density lipoprotein) significantly (P <.001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. Conclusions Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV-infected patients ≥50 years old or with a Framingham score ≥10% was highly efficacious and well tolerated, and improved the lipid profile. Clinical Trials Registration NCT02098837 and EudraCT: 2013-003704-39. [ABSTRACT FROM AUTHOR]

Background: The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. Methods: HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. Results: 1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4–49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2–6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders. Conclusion: Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR. [ABSTRACT FROM AUTHOR]

Background: Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown.Methods: NEAT001/ANRS143 is a randomized trial that showed noninferiority over 96 weeks of ritonavir-boosted darunavir plus raltegravir versus tenofovir disoproxil fumarate/emtricitabine in 805 antiretroviral antiretrovrial-naive HIV-infected adults. We compared changes in whole-blood telomere length measured with quantitative polymerase chain reaction in 201 randomly selected participants (104 raltegravir and 97 tenofovir disoproxil fumarate/emtricitabine). We performed multivariable estimative and predictive linear regression.Results: At week 96, participants receiving tenofovir disoproxil fumarate/emtricitabine had a statistically significant higher gain in telomere length than participants receiving raltegravir. Difference in mean telomere length change between groups (tenofovir disoproxil fumarate/emtricitabine minus raltegravir) from baseline to week 96 adjusted by baseline telomere length was 0.031 (P = .009). This difference was not significantly confounded by age, gender, known duration of HIV infection, CD4 (baseline/nadir), CD8 cells, CD4/CD8 ratio, HIV viral load (baseline/week 96), tobacco and alcohol consumption, statins, or hepatitis C.Conclusion: Antiretroviral-naive HIV-infected adults receiving ritonavir-boosted darunavir and tenofovir disoproxil fumarate/emtricitabine had a significant higher gain in blood telomere length than those receiving ritonavir-boosted darunavir and raltegravir, suggesting a better initial recovery from HIV-associated immunosenescence. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: HCV incidence still appears on the rise in HIV‐infected MSM in France. We assessed the incidence of HCV infection in HIV‐positive and in preexposure prophylaxis (PrEP)‐using MSM. Methods: HIV‐infected, HCV‐negative MSM with serological follow‐up in 2016 and HIV‐negative, HCV‐negative PrEP‐using MSM enrolled from January 2016 to May 2017 in the French Dat’AIDS cohort were analysed to assess the incidence of a primary HCV infection. The incidence of HCV reinfection was also determined in patients having cured a previous infection. Results: Among 10 049 HIV‐infected MSM followed in 2016, 681 patients were already HCV‐infected when entering the study (prevalence 6.8%). Serological follow‐up was available in 2016 for 4151 HCV‐negative patients. Virological follow‐up was available for 478 patients who had cured a previous infection. Fifty‐seven HCV infections occurred in 2016 (42 primary infections, 15 reinfections). Incidence of primary HCV infection, reinfection and overall HCV infection was, respectively, 1.0, 3.1 and 1.2/100 person‐years (PY). From January 2016 to May 2017, 930 HIV‐negative subjects were enrolled for PrEP. Seventeen patients were already HCV‐infected (prevalence 1.8%). Twelve HCV infections occurred during follow‐up (10 primary infections, 2 reinfections) giving an incidence of primary infection of 1.0/100 PY and an overall incidence of 1.2/100 PY. Conclusions: The overall incidence of HCV infection and of a primary HCV infection in HIV‐positive and in PrEP‐using MSM appeared similar in France in 2016 to early 2017. HIV‐positive and PrEP‐using MSM probably share similar at‐risk practices and both should be targeted for preventative interventions. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the risk of virological rebound in HIV-1-infected patients achieving virological suppression on first-line combined ART (cART) according to baseline HIV-1 RNA, time to virological suppression and type of regimen.Patients and Methods: Subjects were 10 836 adults who initiated first-line cART (two nucleoside or nucleotide reverse transcriptase inhibitors + efavirenz, a ritonavir-boosted protease inhibitor or an integrase inhibitor) from 1 January 2007 to 31 December 2014. Cox proportional hazards models with multiple adjustment and propensity score matching were used to investigate the effect of baseline HIV-1 RNA and time to virological suppression on the occurrence of virological rebound.Results: During 411 436 patient-months of follow-up, risk of virological rebound was higher in patients with baseline HIV-1 RNA ≥100 000 copies/mL versus <100 000 copies/mL, in those achieving virological suppression in > 6 months versus <6 months, and lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. Baseline HIV-1 RNA >100 000 copies/mL was associated with virological rebound for ritonavir-boosted protease inhibitors but not for efavirenz or integrase inhibitors. Time to virological suppression >6 months was strongly associated with virological rebound for all regimens.Conclusions: In HIV-1-infected patients starting cART, risk of virological rebound was lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. These data, from a very large observational cohort, in addition to the more rapid initial virological suppression obtained with integrase inhibitors, reinforce the positioning of this class as the preferred one for first-line therapy. [ABSTRACT FROM AUTHOR]

In a double-blind, phase 3 trial, 663 HIV-infected, virologically suppressed adults were randomized to switch to tenofovir alafenamide (TAF; n = 333) vs. remain on tenofovir disoproxil fumarate (TDF; n = 330), each coformulated with emtricitabine (FTC), while continuing their third agent (boosted protease inhibitor or unboosted third agent). At week 96, 88.6% on FTC/TAF and 89.1% on FTC/TDF had HIV-1 RNA <50 copies per milliliter [adjusted difference 20.5% (95% confidence interval: 25.3 to 4.4%)]. Proteinuria, albuminuria, proximal renal tubular function, and bone mineral density improved after switching to TAF-from TDF-containing regimens. These longer-term data support FTC/TAF as a safe, well-tolerated, and durable nucleotide reverse transcriptase inhibitor backbone. [ABSTRACT FROM AUTHOR]

The consensus definition of late presentation for human immunodeficiency virus patient based on a CD4 threshold of 350 cells/mm3 has limitations concerning risk factors identification since there is growing biomedical justification for earlier initiation of treatment. The objective was to overcome this problem by simultaneously determining factors associated with different levels of CD4 counts at the time of diagnosis. Between January 2000 and July 2014, 1179 patients with a first human immunodeficiency virus diagnosis and entering care in a French human immunodeficiency virus reference center were enrolled. Factors associated with each 5 percentile from 5th to 95th quantile of CD4 counts at diagnosis were simultaneously studied in a multivariable quantile regression model. At each of the quantiles, the factors identified as negatively associated with CD4 count at diagnosis were older age, male sex , foreign patients, hepatitis B virus or hepatitis C virus co-infection, employment status, non-MSM transmission, heterosexual transmission, suburban and rural's place of residence and earlier period of diagnosis. Association with CD4 count was not uniformly significant, most factors being significant for some quantiles. The only significant determinant for all quantiles was being born in a foreign country. These results are particularly helpful in the context of human immunodeficiency virus clinical care, management and prevention. [ABSTRACT FROM AUTHOR]

Background: The long-term efficacy of Highly Active Antiretroviral Therapies (HAART) has enlightened the crucial role of health-related quality of life (HRQL) among HIV-infected patients. However, any analysis of such extensive longitudinal data necessitates a suitable handling of dropout which may correlate with patients' health status.Methods: We analysed the HRQL evolution over 5 years for 1,000 patients initiating a protease inhibitor (PI)-containing therapy, using MOS SF-36 physical (PCS) and mental (MCS) scores. In parallel with a classical separate random effects model, we used a joint parameter-dependent selection model to account for non-ignorable dropout.Results: HRQL evolved according to a two-phase pattern, characterized by an initial improvement during the year following HAART initiation and a relative stabilization thereafter. Immunodepression and self-reported side effects were found to be negative predictors of both PCS and MCS scores. Hepatitis C virus coinfection and AIDS clinical stage were found to affect physical HRQL. Results were not significantly altered when accounting for dropout.Conclusion: Such results, obtained on a large sample of HIV-infected patients with extensive follow-up, underline the need for a regular monitoring of patients' immunological status and for a better management of their experience with hepatitis C and HAART. [ABSTRACT FROM AUTHOR]

Objectives: We assessed factors, including treatment course, associated with failure to obtain a 10 year immunological response after starting first-generation PI-containing combined ART (cART).Patients and Methods: In the prospective COPILOTE cohort of HIV-infected patients started on a first-generation PI-containing regimen in 1997-99, the impact of cART history on the failure to achieve immunological response measured at 10 years was assessed by multivariate logistic regression models in the 399 patients with clinical and virological success of cART.Results: Failure of CD4 response (CD4 >500/mm3) was associated with age ≥40 years at baseline (P < 0.001), CD4 cell counts ≤500/mm3 at month 4 (P = 0.016) or month 12 (P < 0.001) and ≥3 months of cART interruption (P = 0.016). Factors associated with failure to achieve complete immunological response (CD4 >500/mm3 and CD4:CD8 ratio >1) were CD4:CD8 ratio ≤0.8 at month 8 (P < 0.001) or month 12 (P < 0.001), ≥3 months of cumulative cART interruption (P = 0.011), ≥3 antiretroviral regimens (P = 0.009) and ≤4 treatment lines (P = 0.015). Baseline CD4 and CD4:CD8 ratio were not predictors of the 10 year immunological outcomes.Conclusions: In this therapeutic cohort of patients starting first-generation PI-containing cART in 1997-99, poor initial immunological response had a negative impact on 10 year CD4 and CD4 plus CD4:CD8 ratio response, despite prolonged virological success. Lack of treatment interruption may improve long-term immunological outcome in HIV infection. [ABSTRACT FROM AUTHOR]

This study's objective was to explore the factors associated with the belief (or not) by people living with HIV that it is easier to talk about their seropositivity 10 years after initiating a protease inhibitor-containing ART. All patients in the ANRS CO8 APROCO-COPILOTE cohort who completed a self-administered questionnaire at 10 years of follow-up were included in this study. Forty-four percent of patients declared that discussing their seropositivity with their family was easier 10 years later, while 28 % declared this was true for discussing their status with a new sexual partner. Having a low socioeconomic status, not receiving social support from a steady partner and declaring a low number of discomforting symptoms 12 months after PI initiation were all independently associated with less difficulty in discussing seropositivity. This study highlights the difficulties in disclosing HIV 10 years after PI initiation, and the important influence of psychosocial factors and patients' daily-life experience on disclosure. [ABSTRACT FROM AUTHOR]