PLoS One

AIM: Metabolic risk factors are poorly documented for the first generation of young adults who have lived with HIV since childhood. We compared their metabolic profile with that of adults of same age from the general population. METHODS: We conducted a cross-sectional analysis of data from two populations: (1) COVERTE (ANRS-CO19), a French national cohort of 18 to 30-year-old patients HIV-infected since childhood, and (2) ENNS, a national cross-sectional population-based household survey on nutrition. Body mass index (BMI), blood pressure, waist circumference, fasting glucose, triglycerides, and HDL-, LDL- and total cholesterol were measured in both studies. Direct standardization on overweight and education level and logistic regression were used to compare the prevalence of metabolic abnormalities between the two populations. RESULTS: Data from 268 patients from COVERTE and 245 subjects from ENNS were analyzed. Tobacco use was similar in both groups. HIV-infected patients had increased mean waist-to-hip ratio and triglycerides to HDL-cholesterol ratio and decreased mean HDL-cholesterol as compared to their counterparts from the general population in both genders. In HIV-infected patients, metabolic syndrome was identified in 13.2% of men (95% confidence interval [CI]: 7.1-19.2) and 10.4% (95% CI: 5.4-15.3) of women versus 10.6% (95%CI: 1.5-19.7) and 1.7% (95%CI: 0-4.1) in subjects from the general population, respectively. CONCLUSION: Young adults infected with HIV since childhood had a higher prevalence of dyslipidemia and metabolically detrimental fat distribution than adults of same age of the general population, supporting close monitoring for cardiometabolic diseases

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Exposition périnatale aux antirétroviraux et devenir des enfants non infectés par le VIH (analyse de la cohorte nantaise de 2000 à 2005)

Grâce à une étude rétrospective portant sur 81 grossesses de mères infectées par le VIH aboutissant à la naissance de 83 enfants entre 2000 et 2005 à Nantes, nous avons voulu faire le point concernant l'exposition périnatale aux antirétroviraux dans le cadre de la prévention de la transmission mère-enfant et sur le devenir des enfants non infectés. Le taux de transmission résiduel était de 1,3. Un quart des enfants était né avant terme. Parmi les enfants non infectés 10 ont présenté des anomalies neurologiques persistantes dont 3 étaient suspects de cytopathie mitochondriale. Près de 40 ont présenté une hyperlactatémie persistante et plus de 40 étaient anémiés à 1 mois. Sans remettre en cause la nécessité de la prophylaxie de la transmission mère-enfant du VIH, il s'avère indispensable de suivre les enfants non infectés sur le long terme.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Neutrophil gelatinase-associated lipocalin, a marker of tubular dysfunction, is not increased in long-term virologically controlled patients receiving a tenofovir/emtricitabine + nevirapine regimen

International audienceOBJECTIVES: Tenofovir may be associated with nephrotoxicity. Several studies have shown that an early increase in urinary neutrophil gelatinase-associated lipocalin (NGAL) may predict the occurrence of acute kidney injury. We investigated urine and plasma NGAL in patients on long-term treatment with nevirapine associated with either tenofovir/emtricitabine or abacavir/lamivudine.PATIENTS AND METHODS: We studied 40 virologically controlled Caucasian patients on stable treatment (median >4 years) with tenofovir/emtricitabine + nevirapine (n = 20) or abacavir/lamivudine + nevirapine (n = 20), and no history of kidney disease, high blood pressure or diabetes. Plasma immunovirological parameters (NGAL and C-reactive protein) and urinary NGAL, β2-microglobulin and α1-microglobulin were measured during a routine clinical visit.RESULTS: Median concentrations of NGAL were in the normal range, but were significantly higher in the abacavir/lamivudine group compared with the tenofovir/emtricitabine group both in the plasma, at 74.9 and 66.0 ng/mL (P = 0.032), respectively, and in the urine, at 36.1 and 12.8 ng/mL (P = 0.017), respectively.CONCLUSIONS: Plasma and urinary NGAL concentrations remained in the normal range in this long-term virologically controlld population without any overt renal disease. The usefulness of NGAL in detecting sub-clinical renal dysfunction appears to be very limited

Nevirapine-raltegravir combination, an NRTI and PI/r sparing regimen, as maintenance antiretroviral therapy in virologically suppressed HIV-1-infected patients.

International audienceNucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI)/ritonavir sparing regimens may be useful to some HIV-infected patients. Nevirapine (NVP) and raltegravir (RAL) are both potent antiretrovirals with good long-term safety profiles. We retrospectively identified from our electronic database all patients with HIV RNA6 months on an NVP-containing regimen and no prior exposure to integrase strand transfer inhibitors who were switched to RAL plus NVP. Data was collected for 36 months or until discontinuation of RAL plus NVP for any reason. A total of 39 patients (30 male) were included in this analysis. Median duration of prior antiretroviral therapy was 14 years (IQR 10-17) and median duration with plasma HIV-1 RNA<50 copies/ml prior to switch was 50 months (IQR 22-96). Switched regimens included mainly a boosted PI (n=24) or tenofovir disoproxil fumarate/emtricitabine (n=12). After switching, the percentages of patients with HIV-1 RNA<50 copies/ml were 87.2% (95% CI 76.7, 97.7) and 82.1% (95% CI 70.0, 94.1) at 6 and 12 months, respectively, in the intent-to-treat-exposed analysis, 97.1% (95% CI 91.6, 100) and 94.1% (95% CI 86.2, 100), respectively, in the per-protocol analysis. All patients with follow-up to month 24 (n=22) or month 36 (n=14) had HIV-1 RNA<50 copies/ml. One virological failure was observed (related to archived non-nucleoside reverse transcriptase inhibitor resistance mutation). During follow-up, no patient experienced Grade 3 or 4 adverse events. Median values of serum creatinine and lipids significantly improved after switch. In patients with prolonged HIV-1 RNA<50 copies/ml, switching to NVP-RAL combination maintained virological suppression throughout 36 months. This combination deserves further evaluation in patients unable to tolerate NRTI or PI/ritonavir agents

T-Cell Receptor Excision Circles in HIV-Exposed, Uninfected Newborns Measured During a National Newborn Screening Program for Severe Combined Immunodeficiency.

International audienceSevere combined immunodeficiency screening by measuring T-receptor excision circles at birth allows evaluation of the impact of various maternal conditions on newborn immunity. The slight decrease observed in a French cohort of newborns to HIV-infected mothers can be explained by the confounding factors of prematurity and African descent