Elevation of brain ADC (apparent diffusion coefficient) in HIV-associated neurocognitive disorders and evolution after treatment: A pilot study.

BACKGROUND: Thirty to 50% of HIV-infected patients develop HIV-Associated Neurocognitive Disorders (HAND) despite virological control. The previously published Neuro+3 study showed their neurocognitive status can be improved by intensifying antiviral therapy. Our study is a part of the Neuro3+ study and aims to study apparent diffusion coefficient (ADC) as a biomarker for neurological improvement. PATIENTS AND METHODS: We prospectively included 31 patients with HAND. They received therapy with better CNS Penetration Effectiveness (CPE) score with two-year follow-up. Cognitive status was assessed at day 0 (D0) and week 96 (W96) using Frascati 3-stage classification and Global Deficit Score (GDS). Brain MRI at D0 and W96 assessed morphological data (white matter hyperintensities, opportunistic infections, ischemic lesions, atrophy) and measured whole brain apparent diffusion coefficient (ADC). We compared their data with a control group of 20 healthy patients with similar ages and sex ratio. RESULTS: After ARV intensification, cognitive status was significantly improved: GDS (n = 1,4 vs 1,0 p = 0.01) and Frascati scale (2HAD/22MND/7ANI vs 1HAD/8MND/17ANI p = 0.001). Mean ADC was significantly higher in patients at inclusion than in controls (0.88 × 10-3 mm2/s ± 0.06 vs 0.81 × 10-3 mm2/s ± 0.04, p = 0.0001). ADC decreased after treatment (0.88 × 10-3 mm2/s ± 0.06 vs 0.85 × 10-3 mm2/s ± 0.06 (p = 0,04). In subgroup analysis, ADC significantly decreased in clinically improved patients (0.89 × 10-3 mm2/s ± 0.07 vs 0.85 × 10-3 mm2/s ± 0.07 (p = 0,03)) and did not significantly change in non-clinically improved patients (0.86 × 10-3 mm2/s ± 0.07 vs 0.84 × 10-3 mm2/s ± 0.07 (p = 0,31)). After treatment, there was no significant difference between patients and controls (0.85 × 10-3 mm2/s ± 0.06 vs 0.81 × 10-3 mm2/s ± 0.04, p = 0.17). CONCLUSION: Whole-brain ADC is a good biomarker of HIV-associated neurocognitive disorders. It is significantly increased in patients with HAND compared with controls and significantly decreases after treatment. It is all the more important to have a quantitative biomarker as conventional imaging does not contribute to the diagnosis.

Improvement of HIV-associated neurocognitive disorders after antiretroviral therapy intensification: the Neuro+3 study.

OBJECTIVES: Despite the effectiveness of antiretroviral (ARV) therapy to control HIV infection, HIV-associated neurocognitive disorders (HAND) remain frequent. The Neuro+3 study assessed the cognitive improvement associated with ARV intensification based on increased CNS penetration effectiveness (CPE) scoring ≥+3 and total CPE score ≥9. METHODS: Thirty-one patients, aged 18-65 years, with confirmed diagnosis of HAND and effective ARV therapy were included. The cognitive improvement was measured using Frascati three-stage classification and global deficit score (GDS) after 48 and 96 weeks of ARV intensification. Ultrasensitive HIV-RNA, neopterin, soluble CD14, CCL2, CXCL10, IL6, IL8 and NF-L were measured in plasma and cerebrospinal fluid at Day 0 (baseline), Week 48 (W48) and W96. RESULTS: The intensified ARV was associated with a median (IQR) CPE score increase from 6 (4-7) at baseline to 10 (9-11). From baseline to W96, the median (IQR) GDS decreased from 1.4 (0.8-2.2) to 1.0 (0.6-2.0) (P = 0.009); HAND classification improved from 2 to 1 HIV-associated dementia, 22 to 8 mild neurocognitive disorders, 7 to 17 asymptomatic neurocognitive impairment and 0 to 5 patients without any neurocognitive alterations (P = 0.001). In multivariable linear regression analysis, GDS improvement at W96 was significantly associated with CPE score ≥9 after intensification (P = 0.014), CD4 lymphocyte increase at W48 (P < 0.001) and plasma CXCL10 decrease at W96 (P = 0.001). CONCLUSIONS: In patients with HAND, a significant cognitive improvement was observed after the ARV intensification strategy, with a higher CPE score. Cognitive improvement was more often observed in the case of a switch of two drug classes, arguing for better control of CNS HIV immune activation.

Bariatric surgery in HIV patients: experience of an Obesity Reference Center in France.

BACKGROUND: Few data on bariatric surgery are available regarding obese human immunodeficiency virus (HIV)-infected patients. SETTINGS: Antoine Beclere hospital, Clamart, Paris-sud University, France METHODS: Prospective observational follow-up study recruited HIV-infected patients who underwent bariatric surgery from 2009 to 2015. Baseline demographic characteristics, surgery characteristics, perioperative outcomes, changes in weight loss, HIV markers, antiretroviral drug plasma levels are described. RESULTS: There were 10 patients followed before and after sleeve gastrectomy: 2 men and 8 women; 50% of African origin; median age, 48.5 years, median time since HIV infection, 7.5 years; median body mass index, 48.5 kg/m2. Of patients, 8 had co-morbidities. All except 2 patients received antiretroviral drugs at the time of surgery with a median CD4 cell count at 709/mm3. There was no death or postoperative infectious complications. The median follow-up was 18 months (range, 15-55). The median postoperative weight loss was 43 kg (range, 17-83). Median percentage of excess weight loss was 82.5% (range, 35-119) at the latest visit after surgery. All co-morbidities were resolutive with weight loss. We observed no significant modification of CD4 cell count before and after surgery. Pharmacokinetics of antiretroviral drugs remains adequate and efficacious. CONCLUSION: Our prospective series is the largest one on sleeve gastrectomy procedures performed on obese-treated HIV-infected patients. The sleeve generates good results in weight loss, with no significant impact on HIV infection, and with improvement of obesity-associated co-morbidities. Optimal management of HIV-infected patients with morbid obesity may include classical surgical procedures.

[Aging and HIV infection: 4 years follow-up of 149 HIV infected patients older than 60 years in West Paris agglomeration (COREVIH Île-de-France Ouest)]. / Vieillissement et infection par le VIH: suivi de 149 patients âgés de plus de 60ans infectés par le VIH (COREVIH Île-de-France Ouest).

UNLABELLED: In France, patients over 50 years represent more than 23.6% of all registered cases in the French Hospital Database for HIV (FHDH), and 18% of newly HIV-diagnosed patients. OBJECTIVE: To describe the long-term evolution after 4 years of a cohort of HIV infected patients older than 60 years recruited in COREVIH Île-de-France Ouest. RESULTS: One hundred and forty-nine participants, 115 men (77%) and 34 women (23%), were included in the cohort analysis in 2004, and baseline characteristics were: median age 65.4 years (60.3-86.3), CDC stage C: 36%, HBV and HCV co-infections: four (2.7%) and eight (5.4%) patients, median time from first HIV infection diagnosis: 8.5 years (0.25-19.5), ongoing HAART regimen: 88%, median duration of ARV treatment: 7.5 years (0.2-15.5), baseline CD4 cells count: 372/mm(3) (18-1860), HIV viral load less than 200 c/ml: 104 (70%). After a 4-year follow-up, 111 patients were alive, all but one treated with HAART, 17/149 (11.5%) were lost for follow-up, and 21/149 were deceased (14%). Causes of death were acute cardiovascular disease (4/21), neoplasia (11/21), neurological disease 1/21, end stage liver disease 3/21, unknown 2/21. The prevalence of co-morbidities after 4 years of follow-up were: arterial hypertension 40/111 (36%), hypercholesterolemia 48/111 (43%), diabetes 23/111 (21%), kidney disease with renal insufficiency (creatinine clairance<60 ml/min): 36/111 (32%). At the end of follow-up, median CD4 cells count was 494/mm(3), and viral load was undetectable less than 200 c/ml in 107/111 patients (96%). No new opportunistic infection occurred during the 4-year follow-up, but 24 patients had a new diagnosis of neoplasia (incidence 40/1000 person-year). Cancer was the cause of death in 11/24. CONCLUSION: Clinical and immunological improvement was continuous under HAART in these aged HIV infected patients, but co-morbidities are frequently observed in this population, with high incidence of cardiovascular disease and neoplasia, and related mortality. A multidisciplinary approach, with preventive consultations, oncology and cardiovascular screening, as done in geriatrics, is warranted in the aging HIV population.

Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study.

To assess the evolution of triglyceride (TG) levels in HIV-infected patients receiving stable potent antiretroviral therapy treated with N-3 polyunsaturated fatty acids (PUFAs), a prospective double-blind randomized design for a reliable assessment of TG evolution was performed. One hundred twenty-two patients with TG levels >2 g/L and < or =10 g/L after a 4-week diet (baseline TG: 4.5 +/- 1.9 g/L) were randomized for 8 weeks to N-3 PUFAs (2 capsules containing 1 g of fish oil 3 times daily, n = 60), or placebo (1 g of paraffin oil capsules, n = 62). An 8-week open-label phase of N-3 PUFAs followed. Evaluation criteria were TG percent change at week 8, percentage of responders (normalization or > or =20% TG decrease), and safety issues. Ten patients with baseline TG levels >10 g/L were not randomized and received N-3 PUFAs as open treatment. The difference (PUFA - placebo) in TG percent change at week 8 was -24.6% (range: -40.9% to -8.4%; P = 0.0033), the median was -25.5% in the PUFA group versus 1% in the placebo group, and mean TG levels at week 8 were 3.4 +/- 1.8 g/L and 4.8 +/- 3.1 g/L, respectively. TG levels were normalized in 22.4% (PUFA) versus 6.5% (placebo) of patients (P = 0.013) with a > or =20% reduction in 58.6% (PUFA) versus 33.9% (placebo) of patients (P = 0.007). Under the open-label phase of N-3 PUFAs, the decrease in TG levels was sustained at week 16 for patients in the PUFA group (mean TG: 3.4 +/- 1.7 g/L), whereas a 21.2% decrease in TG levels occurred for patients in the placebo group (mean TG: 3.3 +/- 1.4 g/L). No significant differences were observed between groups in the occurrence of adverse events. The median TG change at week 8 was -43.6% (range: Q1-Q3; 95% CI: -66.5% to -4.6%) for patients with baseline TG levels >10 g/L. The difference in mean total cholesterol between groups (PUFA - placebo) at week 8 was -8.5% (P = 0.0117). This study demonstrated the efficacy of PUFAs to lower elevated TG levels in treated HIV-infected hypertriglyceridemic patients. N-3 PUFAs have a good safety profile.

[The neuropathology of HIV infection in the era of highly active antiretroviral therapy]. / La pathologie du système nerveux central liée au VIH à l'ère des multithérapies.

Introduction of Highly Active Antiretroviral Treatment (HAART) which is available for most AIDS patients in France since 1996, has resulted in a dramatic improvement of the disease course. From the survey of our autopsy series of (AIDS) cases and the review of other neuropathological studies from different developed countries, we found quantitative and qualitative changes in the pattern of human immunodeficiency virus (HIV) neuropathology. Quantitatively, there was a dramatic decrease in the number of autopsy cases but brain involvement remained a major cause of death in AIDS patients. There was an overall decrease of cerebral toxoplasmosis, cytomegalovirus encephalitis (CMVE) and HIV encephalitis (HIVE) for which successful treatment is available. This contrasted with the unchanged incidence of progressive multifocal leucoencephalopathy (PML) and primary malignant non Hodgkin brain lymphomas (PMBL). However, when looking closer at the last three years, the incidence of diseases affecting patients with severe immunodepression (CMVE, PML, PMBL) decreased in 2000-2002, whereas infections occurring in patients with milder immunodeficiency (toxoplasmosis, varicella-zoster encephalitis (VZVE) or herpes simplex virus encephalitis (HSVE) became more frequent. Qualitatively, there were uncommon types of brain infections, such as BK virus encephalitis or general paresis. Finally, new forms of HIVE were reported: severe leukoencephalopathy with intense perivascular macrophage and lymphocyte infiltration possibly due to an exaggerated response from a newly reconstituted immune system; and also chronic "burnt out" forms of HIVE as VZVE, toxoplasmosis, or PML in which no inflammation and no infectious agent could be detected, likely due to prolonged survival.

Efficacy and safety of a quadruple combination Combivir + abacavir + efavirenz regimen in antiretroviral treatment-naive HIV-1-infected adults: La Francilienne.

OBJECTIVE: To evaluate the safety and efficacy of a protease inhibitor sparing, quadruple therapy (Combivir + abacavir + efavirenz) in antiretroviral treatment-naive HIV-1-infected adults. DESIGN: Multicenter open-label pilot study. Clinical and biological assessments were performed at baseline and at weeks 2, 4, 8, 16, 24, 32, 40, 48. RESULTS: Thirty-one subjects enrolled with a median baseline viral load (VL) of 4.69 log10 copies/mL and CD4 cell count of 322 cells/mm3. At week 48, 90% (intention-to-treat [ITT] switch included) and 77% (ITT switch = failure) patients had a VL <50 copies/mL. These results were similar in the population (n = 13) with a VL >100,000 copies/mL at baseline. Combivir + abacavir + efavirenz demonstrated an early antiretroviral response: 58% of patients had plasma HIV-1 RNA <50 copies/mL at week 8. Using a modified assay, the percentage of patients with VL <5 copies/mL at week 48 was 55% (17/31) and 42% (13/31) using ITT (switch included) and ITT (switch = failure), respectively. Median VL decreased by -4.0 log10 copies/mL at week 48 (ITT). Median CD4+ cell count change from baseline at week 48 was +129 cells/mm3 (ITT). Most patients experienced at least one drug-related adverse event that was not considered treatment-limiting by the investigator. There were no cases of abacavir hypersensitivity reactions. CONCLUSIONS: Safety and efficacy results from this study demonstrated that the quadruple regimen Combivir/abacavir/efavirenz is generally safe and displays potent and durable antiretroviral activity in antiretroviral treatment-naive HIV-1-infected patients, offering a promising therapeutic option in a PI-sparing strategy.