Roland Tubiana

Pierre and Marie Curie University - Paris 6, Lutetia Parisorum, Île-de-France, France

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Publications (159)904.2 Total impact

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    ABSTRACT: Background: Evaluation of long-term tolerance to antiretroviral exposure during pregnancy is required. An increased risk of cancer has been suggested in children exposed in utero to didanosine. Methods: Updated evaluation of cancer incidence in uninfected children exposed to nucleos (t)ide reverse transcriptase inhibitors (NRTIs) in the French Perinatal Study of children born to HIV+ mothers, by cross checking with the National Cancer Registry. Associations between cancer risk and exposure to NRTIs were evaluated by univariate survival analysis and Cox proportional hazard models. Standardized incidence ratios (SIR) were used for comparison with the general population. Findings: Twenty one cancers were identified in 15163 children (median age: 9.9 years [interquartile range (IQR): 5.8-14.2]) exposed to at least one NRTI in utero, between 1990 and 2014. Five children were exposed to zidovudine monotherapy, and 15 to various combinations, seven including didanosine. Didanosine accounted for only 10% of prescriptions but was associated with one third of cancers. In a multivariate analysis, didanosine exposure was significantly associated with higher risk (HR = 3.0 [0.9-9.8]). The risk was specifically linked with first-trimester exposure (HR = 5.5 [2.1-14.4]). Overall, the total number of cases was not significantly different from that expected for the general population (SIR = 0.8 [0.47-1.24]), but was twice that expected after didanosine exposure (SIR = 2.5 [1.01-5.19]). Interpretation: There are strong arguments to suggest that didanosine displays transplacental oncogenicity. Although not extrapolable to other NRTIs, they stress the need for comprehensive evaluation of the transplacental genotoxicity of this antiretroviral class.
    No preview · Article · Feb 2016 · AIDS
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    ABSTRACT: We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure.
    Preview · Article · Jan 2016 · PLoS Neglected Tropical Diseases
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    ABSTRACT: Objectives: To investigate the potential for combination antiretroviral therapy (cART)-free remission following analytic treatment interruption (ATI) in chronically HIV-infected patients with ultralow cell-associated DNA. Methods: Pilot study of patients (pts) with plasma viral load (pVL) less than 50 copies/ml for more than 2 years on cART, CD4 above 500 cells/μl, CD4/CD8 above 0.9, CD4 nadir above 300 cells/μl and HIV-DNA above 100 copies/10 peripheral blood mononuclear cells (PBMCs), undergoing treatment interruption. Ultrasensitive pVL, CD4 cell count, triplicate HIV-DNA were measured at D0, W2, W4, and every 4 weeks off-ART until W48 and at W4, W12 and W24 after ART resumption (RxR). RxR occurred in case of pVL rebound above 400 copies/ml or CD4 above 400 cells or HIV-related clinical event. The primary endpoint was the percentage of patients who did not reach RxR criteria at W24. Individuals were to be enrolled in three cohorts of five. Enrolment in cohort 2 began if at least one of five patients from cohort 1 remained in success at W8. Cohort 3 did not start. Results: Ten patients were enrolled, with median (range) CD4 1118 cells/μl (608-1494), CD4/CD8 2.1(1.4-2.6), HIV-DNA 66 copies/10 PBMC (<66-66) at screening, viral suppression of 4.9 years (2.9-8.3), CD4 nadir 495 cells/μl (330-739). One patient remained off-ART up to W48. Viral rebound occurred in nine of 10 patients at W2 (2 patients), W4 (6 patients) and W12 (one patients). pVL was resuppressed on cART at W4 (8 patients) and W12 (one patients). HIV DNA returned to baseline values within a median of 12 weeks following RxR. Conclusion: In a highly selected population of 10 patients with chronic HIV infection, an excellent immune status, durable virological suppression and ultralow reservoir, the success rate of ATI was 10% (95% confidence interval 0.3-44.5%) and nine of 10 patients had prompt rebound of plasma viremia. Resumption of ART led to return to baseline cell-associated total DNA.
    No preview · Article · Jan 2016 · AIDS (London, England)
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    ABSTRACT: Background: The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT. Methods: A total of 8075 HIV-infected mother/infant pairs included from 2000 to 2011 in the national prospective multicenter French Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with determined HIV infection status, and did not breastfeed. PT was analyzed according to maternal VL at delivery and timing of ART initiation. Results: The overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651 infants born to women who were receiving ART before conception, continued ART throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95% confidence interval [CI], 0.1%). VL and timing of ART initiation were independently associated with PT in logistic regression. Regardless of VL, the PT rate increased from 0.2% (6 of 3505) for women starting ART before conception to 0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting during the first, second, or third trimester (P < .001). Regardless of when ART was initiated, the PT rate was higher for women with VLs of 50-400 copies/mL near delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9-8.2). Conclusions: Perinatal HIV-1 transmission is virtually zero in mothers who start ART before conception and maintain suppression of plasma VL.
    No preview · Article · Jul 2015 · Clinical Infectious Diseases
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    ABSTRACT: The aims of this study were to describe the unbound and total lopinavir pharmacokinetics in pregnant women in order to: evaluate if a dosing adjustment is necessary during pregnancy. Lopinavir placental transfer was described and several genetic covariates were tested to explain its variability. A total of 400 maternal, 79 cord blood and 48 amniotic fluid concentrations were collected in 208 women for pharmacokinetic analysis. Among the maternal concentrations, 79 samples were also used to measure the unbound LPV concentrations. A population pharmacokinetics models were developed by using NONMEM software. Two models were developed to describe: the unbound and the total LPV pharmacokinetics, and the LPV placental transfer. The pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. A pregnancy effect was found on the maternal clearance (39 % increases) whereas the treatment group (mono versus triple therapy) or the genetic polymorphisms did not explain pharmacokinetics or placental transfer of LPV. Efficient unbound LPV concentrations in non-pregnant women are similar to those measured during the third trimester of pregnancy. Our study has shown a 39% increase of maternal total concentration clearance during pregnancy whereas unbound LPV concentrations were similar to those simulated in non-pregnant women. The genetic polymorphisms selected did not influence the LPV pharmacokinetics and placental transfer. Thus, we suggest to do not increase LPV dosage during pregnancy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    No preview · Article · Jul 2015 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Characterization of the conditions favouring HIV-1 low-level viraemia (LLV) during treatment is required to guide strategies for prevention and cure. The characteristics and treatments of 171 patients experiencing a confirmed LLV of 50-1000 copies/mL (PLLVs) were compared with those of 146 patients with persistently controlled viraemia. We analysed the risk factors for LLV, the parameters affecting the level of viraemia and the presence of resistance-associated mutations (RAMs). We compared outcomes for PLLVs on fully effective HAART as a function of treatment modifications. LLV was <500 copies/mL in at least 90% of cases. A higher zenith viral load (VL) (5.27 versus 4.91 log10 copies/mL, OR 2.23; P = 0.0003), a shorter time on continuous HAART (4.3 versus 6.8 years, OR 0.88; P = 0.0003) and previously detected RAMs (43% versus 23%, OR 2.42; P = 0.0033) were independent predictors of LLV. NNRTIs were less frequently used in PLLVs and were associated with more stable treatment. The presence of any RAM during LLV was associated with a lower zenith VL and a higher LLV. In the absence of resistance, virological success was achieved in similar proportions of patients with and without treatment modification. Viraemia >500 copies/mL should no longer be considered to be LLV. In patients with a high zenith VL, several years on continuous HAART may be required to decrease the HIV reservoir and prevent LLV. Resistance testing is useful to detect RAMs, leading if necessary to treatment modifications. In the absence of resistance, treatment changes seemed dispensable. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Apr 2015 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Background: Antiretroviral (ARV) regimens during pregnancy are highly effective in preventing mother-to-child transmission of human immunodeficiency virus (HIV). Congenital heart defects (CHDs) and anomalies in cardiac function have been reported in zidovudine (ZDV)-exposed uninfected children. We explored these associations in a large observational cohort and a randomized clinical trial. Methods: Since 1986, the French Perinatal Cohort prospectively enrolled all HIV-infected women in 90 centers and collected follow-up on their children through 2 years of age. All CHDs were reviewed by a specialist blinded to exposures. Additionally, in a randomized trial (PRIMEVA ANRS 135) of 2 ARV regimens during pregnancy, 1 of which was without nucleoside reverse transcriptase inhibitors, infants had a specific follow-up including echocardiography at 1 month and 12 months. Results: Among 12 888 children included, ZDV exposure in the first trimester was significantly associated with CHD (1.5% vs 0.7%; adjusted odds ratio, 2.2 [95% confidence interval, 1.3-3.7]; P < .001). This association was significant for ventricular septal defects (1.1% vs 0.6%; P = .001) and other CHDs (0.31% vs 0.11%; P = .02). In the randomized trial, among 50 infants, girls (but not boys) exposed in utero to ZDV/lamivudine/ritonavir-boosted lopinavir (LPV/r) had a higher left ventricular shortening fraction at 1 month (40% vs 36%; P = .008), and an increased posterior wall thickness at 1 year (5.4 mm vs 4.4 mm; P = .01) than the LPV/r group. Conclusions: This study confirms a specific association between in utero exposure to ZDV and CHDs, and a long-lasting postnatal myocardial remodeling in girls. A potential common mechanism, including the involvement of mitochondrial dysfunction, must be explored, and long-term consequences on cardiac function warrant specific attention. Clinical trials registration: NCT00424814.
    No preview · Article · Apr 2015 · Clinical Infectious Diseases
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    ABSTRACT: Background: Dolutegravir has shown in vitro activity against human immunodeficiency virus type 2 (HIV-2). We report safety and efficacy data of regimens containing dolutegravir (50 mg twice daily) in antiretroviral-experienced, HIV-2-infected patients. Methods: HIV-2-infected patients experiencing virological failure to raltegravir received dolutegravir with optimized background antiretroviral combinations within the French Named Patient Program (NPP). Plasma HIV-2 RNA (pVL) was assessed at time of dolutegravir initiation (baseline), month 3, and month 6. Antiretroviral trough plasma concentrations (C12h) were determined using liquid chromatography coupled with tandem mass spectrometry. Results: Thirteen HIV-2-infected-patients, with a median duration of 15 years' infection and given 16 previous antiretroviral regimens, were included in NPP. Median follow-up was 9 months (min-max, 3-15 months). Median baseline pVL and CD4 cell count were 9544 copies/mL (inter quartile range [IQR], 3096-23 120 copies/mL) and 100 cells/µL (IQR, 77-171 cells/µL), respectively. Available integrase genotypic resistance patterns were Y143C/G/H/R (n = 5), Q148R/K (n = 2), and N155H (n = 4). Optimized background antiretroviral regimens conferring a genotypic sensitivity score ≤2 in 10 patients included nucleoside reverse transcriptase inhibitors associated with darunavir/ritonavir (n = 12), saquinavir/ritonavir (n = 2), and maraviroc (n = 3). At months 3 and 6, pVL was undetectable in 6 of 13 and 4 of 12 patients, respectively, and median CD4 count was 161 (101-188) cells/µL and 167 (135-1353) cells/µL, respectively. Median dolutegravir C12h was 4086 (1756-5717 ng/mL) ng/mL in 9 patients. No serious events were notified except 1 death from progressive multifocal leukoencephalopathy at month 4. Conclusions: Optimized dolutegravir-containing antiretroviral regimens supported by good plasma exposure provide a substantial initial efficacy rate for salvage therapy in heavily antiretroviral-experienced HIV-2-infected patients with virus harboring resistance to first-generation integrase inhibitors. Larger numbers of patients and longer follow-up are needed to confirm these findings.
    No preview · Article · Feb 2015 · Clinical Infectious Diseases
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    ABSTRACT: Atazanavir/ritonavir (ATV/r) is a boosted protease inhibitor recommended to minimize the risk of mother-to-child HIV-1 transmission (MTCT). We aimed to assess the pharmacokinetics, safety and efficacy of ATV/r in HIV-1 infection pregnant women and their neonates. A multicenter, cross-sectional, non-interventional cohort of HIV-1-infected pregnant women receiving ATV/r (300/100 mg once-daily) who delivered in 3 Paris hospitals from 2006 to 2013 was designed. We determined antiretroviral trough plasma concentrations using liquid chromatography-mass spectrometry at each of the 3 trimesters, delivery and post-partum. ATV concentrations at 24 h (C24h) were interpreted by the 150-850 ng/mL efficacy-tolerance thresholds. Safety data and newborn HIV status were recorded. Mother's virologic failure was defined as 2 successive plasma HIV-1-RNA>50 copies/mL within the 2 months before delivery. 103 pregnant women were included, mostly from Sub-Saharan Africa (88%). ATV C24h at each of the 3 trimesters and delivery remained similar to post-partum values. No dose adjustment was needed during pregnancy. The median plasma ratio of fetal/maternal ATV level was 0.19 (n=28). Only 3 patients showed two successive detectable viral loads (VL) but <400 copies/mL. Among 82 available newborn data, 16 were born preterm. Three in utero deaths occurred. Tolerance was good with one case of maternal grade-3 hyperbilirubinemia, no cases in neonates at delivery, and no clinically relevant adverse event. No case of MTCT was reported. In this population, ATV/r-containing antiretroviral regimen demonstrated good pharmacokinetics, virologic efficacy and safety. No significant impact of pregnancy on ATV C24h was found. No dose adjustment was required.
    No preview · Article · Jan 2015 · Antiviral therapy
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    ABSTRACT: With effective antiretroviral therapy, the risk of mother to child transmission (MTCT) is now under 1%. The 2013 French guidelines emphasize early antiretroviral lifelong antiretroviral therapy. Thus, the current trend for women living with HIV is to take antiretroviral therapy before, during and after their pregnancies. A major issue today is the choice of antiretroviral drugs, to maximize the benefits and minimize the risks of fetal exposure. This requires interdisciplinary care. The use of effective therapies permits gradual but profound changes in obstetric practice. When maternal plasma viral load is controlled (<50 copies/ml), obstetrical care can be more similar to standards in HIV-negative women. Prophylactic cesarean section is recommended when the viral load in late pregnancy is above 400 copies/mL. Intravenous zidovudine during labor is recommended only if the last maternal viral load is > 400 copies/mL or in case of complications such as preterm delivery, bleeding or chorio-amnionitis during labor. In case of premature rupture of membranes before 34 weeks, a multidisciplinary decision should be made, based on gestational age and control of maternal viral load; if the woman is under antiretroviral therapy and especially if her viral load is undetectable, steroids and antibiotics should be offered and pregnancy can be continued except in case of signs or symptoms of chorio-amnionitis. Breastfeeding is not recommended in women living with HIV in France, as in industrialized countries. Prophylaxis in the newborn is usually zidovudine for 1 month. In case of significant exposure to HIV perinatally, in particular when, maternal viral load is > 1000 copies/mL, prophylactic combination therapy is recommended. Monitoring of the child is necessary to determine whether or not it is free of HIV infection and to monitor possible adverse effects of perinatal exposure to antiretroviral drugs.
    No preview · Article · Dec 2014 · La Revue Sage-Femme
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    ABSTRACT: A majority of HIV-1-infected patients present a severe deficit in vitamin D, which predicts short-term mortality. Vitamin D is a naturally synthesized hormone, with important immunomodulatory functions. In the general population, its deficit has been associated with increased markers of inflammation. Vitamin D deficit may therefore play a role in the establishment of elevated systemic immune activation, which persists despite suppressive antiretroviral therapy (ART) in HIV-infected patients, and is predictive of disease progression; and vitamin D supplementation may be beneficial in this context. We performed both a cross-sectional study (vitamin D deficit versus normal level) and a longitudinal study (upon vitamin D supplementation for 6 to 12 months) of HIV-1-infected patients receiving suppressive ART. The primary outcome measure was the percentage of activated memory CD8 T cells in blood, which is a robust marker associated with disease progression. Secondary outcomes included general T-lymphocyte and B-lymphocyte phenotype. Although vitamin D deficiency had no influence on T-cell and B-cell subset distribution, we found an association between vitamin D and immune activation levels in HIV-1-infected patients. Vitamin D supplementation in vitamin D-deficient patients resulted in reduced immune activation levels. The present data support the rationale of vitamin D supplementation in the routine clinical management of HIV-1-infected patients, in order to decrease immune activation levels and possibly improve long-term survival.
    No preview · Article · Nov 2014 · AIDS (London, England)
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    Preview · Article · Sep 2014 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: The distribution and evolution of X4/R5 viral tropism during HIV-2 infection remains unknown. HIV-2 tropism was assessed in 83 antiretroviral-experienced patients with virological failure. Tropism was predicted as X4 in 58% of patients and was associated with a CD4 cell count of less than 100 cells/μl, and with a higher number of drug resistance mutations. This high prevalence of X4 virus might compromise the use of CCR5 inhibitors, currently mostly considered in HIV-2 salvage therapy of highly pretreated patients.
    No preview · Article · Sep 2014 · AIDS (London, England)
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    ABSTRACT: Objectives: To evaluate whether a dual nucleoside reverse transcriptase inhibitor (NRTI) strategy can control HIV replication in antiviral therapy (ART)-naive HIV-infected patients with a high CD4 cell count and a low viral load (VL). Methods: This observational study included all HIV-infected treatment-naive patients with a CD4 cell count >300 cells/mm(3), a plasma HIV RNA between 1000 copies/mL and 30,000 copies/mL and wild-type virus who initiated dual NRTI ART between January 2008 and December 2012. HIV RNA and CD4 cell count were assessed at Day 0, Week (W) 4, W12, W24 and W48. The primary endpoint was the proportion of patients with a plasma VL (pVL) <50 copies/mL at W24. Results: Twenty patients were included. The median (IQR) baseline characteristics were: time since HIV diagnosis, 25 months (8-66 months); CD4 cell count, 592 cells/mm(3) (405-798 cells/mm(3)); HIV RNA, 10,395 copies/mL (4106-16,566 copies/mL); and HIV DNA, 464 copies/10(6) peripheral blood mononuclear cells (195-1168 copies/10(6) PBMC). Nineteen patients received tenofovir/emtricitabine and one patient received abacavir/lamivudine. At W12, 88% of the patients with available data (n = 16/18, 95% CI 0.65-0.99) had a pVL <50 copies/mL. Overall, the proportion of patients with a pVL <50 copies/mL was 100% (n = 20/20, 95% CI 0.83-1.0) at W24 and 95% (n = 18/19, 95% CI 0.74-0.99) at W48 (with one patient lost to follow-up and one patient with poor treatment compliance). The median increase in CD4 cells was 83 cells/mm(3) (40-310 cells/mm(3)). There was no discontinuation of antiretroviral therapy for any reason such as lack of efficacy or toxicity. Conclusions: This pilot study suggests that, in patients with a high CD4 cell count and a low VL, a dual NRTI strategy may represent a potentially effective treatment strategy to control HIV replication. This needs to be confirmed in larger controlled clinical studies.
    No preview · Article · Jul 2014 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Lopinavir is an HIV protease inhibitor with high protein binding (98-99%) in human plasma. This study was designed to develop an ultrafiltration method to measure the unbound concentrations of lopinavir overcoming the non-specific binding issue. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of total concentrations of lopinavir in plasma was developed and validated, and an adaptation was also optimized and validated for the determination of unbound concentrations. The chromatographic separation was performed with a C18 column (100mm×2.1mm i.d., 5μm particle size) using a mobile phase containing deionized water with formic acid, and acetonitrile, with gradient elution at a flow-rate of 350μLmin(-1). Identification of the compounds was performed by multiple reaction monitoring, using electrospray ionization in positive ion mode. The method was validated over a clinical range of 0.01-1μg/mL for human plasma ultrafiltrate and 0.1-15μg/mL in human plasma. The inter and intra-assay accuracies and precisions were between 0.23% and 11.37% for total lopinavir concentrations, and between 3.50% and 13.30% for plasma ultrafiltrate (unbound concentration). The ultrafiltration method described allows an accurate separation of the unbound fraction of lopinavir, circumscribing the loss of drug by nonspecific binding (NSB), and the validated LC-MS/MS methodology proposed is suitable for the determination of total and unbound concentrations of lopinavir in clinical practice.
    No preview · Article · Jul 2014 · Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
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    ABSTRACT: The desire for children is a legitimate aspiration that should be part of multidisciplinary care for all men, women or couples living with HIV. The use of effective antiretroviral therapy has revolutionized the prevention of sexual, as well as mother-to-child HIV transmission. When the HIV plasma viral load is undetectable on long-term antiretroviral therapy, the risk of mother-to-child transmission is <1% and the risk of heterosexual HIV transmission without condom use in a stable relationship is very low (estimated at less than 1/10,000) in the absence of inflammation of the genital tract. In a man with a long-term undetectable viral load, viral shedding in semen is uncommon, but may occur persistently or intermittently. The same appears true of viral shedding in the vaginal tract of women. Reproductive options are: natural conception, self-insemination when the woman is HIV-infected, assisted reproduction. Natural conception is now considered to be an acceptable option when the conditions are met, after exploring four aspects: (1) virological (viral load undetectable sustained for at least 6 months on therapy), (2) genital (absence of genital infections or lesions), (3) fertility (after appropriate evaluation) and (4) detecting the ovulation period to limit intercourse without condoms. Assisted reproduction has two objectives in the context of HIV, to allow the couple to conceive without abandoning condom use and/or to treat infertility.
    No preview · Article · Jul 2014 · Gynécologie Obstétrique & Fertilité
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    ABSTRACT: Background Despite control of HIV infection under antiretroviral therapy (ART), immune T-cell activation persists in patients with controlled HIV infection, who are at higher risk of inflammatory diseases than the general population. PMNs play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in cases of excessive or misdirected responses. Objective The aim of our study was to analyze PMN functions in 60 ART-treated and controlled HIV-infected patients (viral load, <20 RNA copies/mL; CD4 count, ≥350 cells/mm3) with (HIV[I] group) and without (HIV[NI] group) diseases related to an inflammatory process and to compare them with 22 healthy control subjects. Methods Flow cytometry was used to evaluate PMN functions in whole-blood conditions. We studied in parallel the activation markers of T lymphocytes and monocytes and the proinflammatory cytokine environment. Results Blood samples from HIV-infected patients revealed basal PMN hyperactivation associated with deregulation of the apoptosis/necrosis equilibrium. Interestingly, this hyperactivation was greater in HIV(I) than HIV(NI) patients and contrasted with a lack of monocyte activation in both groups. The percentage of circulating cells producing IL-17 was also significantly higher in HIV-infected patients than in control subjects and was positively correlated with markers of basal PMN activation. In addition, the detection of IL-22 overproduction in HIV(NI) patients suggests that it might contribute to counteracting chronic inflammatory processes during HIV infection. Conclusions This study thus demonstrates the presence of highly activated PMNs in HIV-infected patients receiving effective ART and the association of these cells with a specific IL-17/IL-22 environment.
    Full-text · Article · Jul 2014 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: The desire for children is a legitimate aspiration that should be part of multidisciplinary care for all men, women or couples living with HIV. The use of effective antiretroviral therapy has revolutionized the prevention of sexual, as well as mother-to-child HIV transmission. When the HIV plasma viral load is undetectable on long-term antiretroviral therapy, the risk of mother-to-child transmission is <1% and the risk of heterosexual HIV transmission without condom use in a stable relationship is very low (estimated at less than 1/10,000) in the absence of inflammation of the genital tract. In a man with a long-term undetectable viral load, viral shedding in semen is uncommon, but may occur persistently or intermittently. The same appears true of viral shedding in the vaginal tract of women. Reproductive options are: natural conception, self-insemination when the woman is HIV-infected, assisted reproduction. Natural conception is now considered to be an acceptable option when the conditions are met, after exploring four aspects: (1) virological (viral load undetectable sustained for at least 6 months on therapy), (2) genital (absence of genital infections or lesions), (3) fertility (after appropriate evaluation) and (4) detecting the ovulation period to limit intercourse without condoms. Assisted reproduction has two objectives in the context of HIV, to allow the couple to conceive without abandoning condom use and/or to treat infertility.
    No preview · Article · Jun 2014 · Gynécologie Obstétrique & Fertilité
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    ABSTRACT: With effective antiretroviral therapy, the risk of mother to child transmission (MTCT) is now under 1%. The 2013 French guidelines emphasize early antiretroviral lifelong antiretroviral therapy. Thus, the current trend for women living with HIV is to take antiretroviral therapy before, during and after their pregnancies. A major issue today is the choice of antiretroviral drugs, to maximize the benefits and minimize the risks of fetal exposure. This requires interdisciplinary care. The use of effective therapies permits gradual but profound changes in obstetric practice. When maternal plasma viral load is controlled (<50 copies/ml), obstetrical care can be more similar to standards in HIV-negative women. Prophylactic cesarean section is recommended when the viral load in late pregnancy is above 400 copies/mL. Intravenous zidovudine during labor is recommended only if the last maternal viral load is>400 copies/mL or in case of complications such as preterm delivery, bleeding or chorio-amnionitis during labor. In case of premature rupture of membranes before 34 weeks, a multidisciplinary decision should be made, based on gestational age and control of maternal viral load; if the woman is under antiretroviral therapy and especially if her viral load is undetectable, steroids and antibiotics should be offered and pregnancy can be continued except in case of signs or symptoms of chorio-amnionitis. Breastfeeding is not recommended in women living with HIV in France, as in industrialized countries. Prophylaxis in the newborn is usually zidovudine for 1 month. In case of significant exposure to HIV perinatally, in particular when, maternal viral load is>1000 copies/mL, prophylactic combination therapy is recommended. Monitoring of the child is necessary to determine whether or not it is free of HIV infection and to monitor possible adverse effects of perinatal exposure to antiretroviral drugs.
    No preview · Article · Jun 2014 · Journal de Gynécologie Obstétrique et Biologie de la Reproduction

  • No preview · Article · May 2014 · European Journal of Clinical Investigation

Publication Stats

5k Citations
904.20 Total Impact Points

Institutions

  • 2006-2016
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2014-2015
    • UPMC
      Pittsburgh, Pennsylvania, United States
  • 2012-2015
    • Polytech Paris-UPMC
      Lutetia Parisorum, Île-de-France, France
  • 1999-2015
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • • Service des Maladies Infectieuses et Tropicales
      • • Service de Virologie
      • • Service d’Hépato - Gastro - Entérologie
      Lutetia Parisorum, Île-de-France, France
  • 2003-2014
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
  • 2010-2013
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2011-2012
    • Assistance Publique – Hôpitaux de Paris
      • Département de Virologie
      Lutetia Parisorum, Île-de-France, France
  • 2010-2011
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2008
    • Sikkim Manipal Institute of Technology
      Rungpo, Sikkim, India
  • 1998-2004
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      • Service des Maladies Infectieuses et Tropicales
      Lutetia Parisorum, Île-de-France, France
  • 2001
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France