Roland Tubiana

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

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Publications (134)728.26 Total impact

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    ABSTRACT: 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).
    Journal of Antimicrobial Chemotherapy 07/2014; · 5.34 Impact Factor
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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.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 07/2014; 965C:216-223. · 2.78 Impact Factor
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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.
    Gynécologie Obstétrique & Fertilité 06/2014; · 0.55 Impact Factor
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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.
    Journal de gynecologie, obstetrique et biologie de la reproduction. 06/2014;
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    ABSTRACT: Antiretroviral therapy (ART) has major benefits during pregnancy, both for maternal health and to prevent mother-to-child transmission of HIV. Safety issues, including teratogenic risk, need to be evaluated. We estimated the prevalence of birth defects in children born to HIV-infected women receiving ART during pregnancy, and assessed the independent association of birth defects with each antiretroviral (ARV) drug used. The French Perinatal Cohort prospectively enrolls HIV-infected women delivering in 90 centers throughout France. Children are followed by pediatricians until 2 y of age according to national guidelines. We included 13,124 live births between 1994 and 2010, among which, 42% (n = 5,388) were exposed to ART in the first trimester of pregnancy. Birth defects were studied using both European Surveillance of Congenital Anomalies (EUROCAT) and Metropolitan Atlanta Congenital Defects Program (MACDP) classifications; associations with ART were evaluated using univariate and multivariate logistic regressions. Correction for multiple comparisons was not performed because the analyses were based on hypotheses emanating from previous findings in the literature and the robustness of the findings of the current study. The prevalence of birth defects was 4.4% (95% CI 4.0%-4.7%), according to the EUROCAT classification. In multivariate analysis adjusting for other ARV drugs, maternal age, geographical origin, intravenous drug use, and type of maternity center, a significant association was found between exposure to zidovudine in the first trimester and congenital heart defects: 2.3% (74/3,267), adjusted odds ratio (AOR) = 2.2 (95% CI 1.3-3.7), p = 0.003, absolute risk difference attributed to zidovudine +1.2% (95% CI +0.5; +1.9%). Didanosine and indinavir were associated with head and neck defects, respectively: 0.5%, AOR = 3.4 (95% CI 1.1-10.4), p = 0.04; 0.9%, AOR = 3.8 (95% CI 1.1-13.8), p = 0.04. We found a significant association between efavirenz and neurological defects (n = 4) using the MACDP classification: AOR = 3.0 (95% CI 1.1-8.5), p = 0.04, absolute risk +0.7% (95% CI +0.07%; +1.3%). But the association was not significant using the less inclusive EUROCAT classification: AOR = 2.1 (95% CI 0.7-5.9), p = 0.16. No association was found between birth defects and lopinavir or ritonavir with a power >85% for an odds ratio of 1.5, nor for nevirapine, tenofovir, stavudine, or abacavir with a power >70%. Limitations of the present study were the absence of data on termination of pregnancy, stillbirths, tobacco and alcohol intake, and concomitant medication. We found a specific association between in utero exposure to zidovudine and heart defects; the mechanisms need to be elucidated. The association between efavirenz and neurological defects must be interpreted with caution. For the other drugs not associated with birth defects, the results were reassuring. Finally, whatever the impact that some ARV drugs may have on birth defects, it is surpassed by the major role of ART in the successful prevention of mother-to-child transmission of HIV. Please see later in the article for the Editors' Summary.
    PLoS Medicine 04/2014; 11(4):e1001635. · 15.25 Impact Factor
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    ABSTRACT: Previous studies on HIV quasispecies have revealed HIV compartmentalization in various tissues within an infected individual. Such HIV variation is a result of a combination of factors including high replication and mutation rates, recombination, and APOBEC3-host selective pressure. To evaluate the differential impact of APOBEC3 editing in HIV-1 compartments, we analyzed the level of G-to-A hypermutation in HIV-1 protease and reverse transcriptase sequences among 30 HAART-treated patients for whom peripheral blood mononuclear cells and body tissues or fluids [cerebral spinal fluid (CSF), rectal tissue, or renal tissue] were collected on the same day. APOBEC3-mediated hypermutation was identified in 36% (11/30) of participants in at least one viral reservoir. HIV hypermutated sequences were often observed in viral sanctuaries (total n = 10; CSF, n = 6; renal tissue, n = 1; rectal tissue n = 3) compared with peripheral blood (total n = 4). Accordingly, APOBEC3 editing generated more G-to-A drug resistance mutations in sanctuaries: three patients' CSF (i.e., G73S in protease; M184I, M230I in reverse transcriptase) and two other patients' rectal tissues (M184I, M230I in reverse transcriptase) while such mutations were absent from paired peripheral blood mononuclear cells. APOBEC3-induced mutations observed in peripheral blood underestimate the overall proportion of hypermutated viruses in anatomical compartments. The resulting mutations may favor escape to antiretrovirals in these compartments in conjunction with a lower penetration of drugs in some sanctuaries. On the other side, because hypermutated sequences often harbor inactivating mutations, our results suggest that accumulation of defective viruses may be more dominant in sanctuaries than in peripheral blood of patients on effective HAART.
    AIDS (London, England) 01/2014; · 4.91 Impact Factor
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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.
    Journal de Gynécologie Obstétrique et Biologie de la Reproduction. 01/2014;
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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.
    Gynécologie Obstétrique & Fertilité 01/2014; · 0.55 Impact Factor
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    ABSTRACT: The relevance of low-level HIV DNA in patients who have undergone prolonged therapy is not well understood. The objective of this study was to determine factors that influence the establishment of low-level HIV DNA in long-term treated patients (excluding treatment since acute infection). This was a cross-sectional study involving 243 patients receiving highly active antiretroviral therapy (HAART) for ≥6 months (median: 9 years of treatment) with plasma HIV RNA <50 copies/mL at the study timepoint, for whom total DNA measurements were performed. Patients treated since early acute infection or receiving cancer chemotherapeutic/immunosuppressive agents were excluded from the study. Overall, the median HIV DNA was 372 copies/10(6) peripheral blood mononuclear cells (PBMCs). Forty-seven patients had levels of HIV DNA below the limit of detection and 58 patients had low-level HIV DNA (<100 copies/10(6) PBMCs). In multivariate analysis, a low total HIV DNA in HAART-treated patients was clearly associated with a low HIV RNA pre-therapeutic viral load (P < 0.0001), regardless of the cut-off used. These results may be helpful to identify candidates for future trials aiming at a functional cure of HIV infection, since low total HIV DNA levels will most likely be a prerequisite of successful immunological control of HIV replication.
    Journal of Antimicrobial Chemotherapy 11/2013; · 5.34 Impact Factor
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    ABSTRACT: The lack of antiretroviral (ARV) backbone activity associated with raltegravir has been proposed as the main explanation for virological relapse observed in patients with undetectable viraemia who are switched from a ritonavir-boosted protease inhibitor (PI) to raltegravir. However ARV activity remains difficult to assess in this context. The aim of our study was to precisely assess the ARV backbone activity in patients with undetectable viraemia who underwent raltegravir switching strategies and to evaluate the efficacy of such switching strategies based on the genotypic sensitivity score (GSS). Patients with a plasma human immunodeficiency virus type 1 (HIV-1) RNA level of <50 copies/mL on a stable two ARV-class regimen were enrolled if they switched one of their ARV drugs to raltegravir 400 mg twice daily. The GSS was calculated using a genotyping test performed on the HIV-1 RNA of the last plasma measurement with a HIV-1 RNA level of >50 copies/mL before the switch and on the results of all previous genotyping tests. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24. Fifty-six patients were enrolled in this study. The proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24 was 92.9 % (range 83.0-97.2 %) in the intent-to-treat analysis and 98.1 % (90.0-99.7 %) in per-protocol analysis. When the backbone was fully active, the proportion was 100.0 % (86.7-100.0 %) at week 24 and week 48 in the per-protocol analysis. We observed a decrease in plasma total cholesterol and triglycerides of -12.7 % (p = 0.005) and -26.5 % (p = 0.001), respectively. Raltegravir switching strategies are effective when the associated backbone is fully active according to the GSS. In the context of undetectable viraemia, where ARV activity remains difficult to assess, the determination of the GSS requires the entire ARV history of the patient and all previous HIV-RNA genotyping test results.
    Infection 10/2013; · 2.44 Impact Factor
  • JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2013; 63(5):e159-63. · 4.65 Impact Factor
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    ABSTRACT: There are today HIV-infected patients in therapeutic impasses because of highly multidrug-resistant (HMDR) viruses. We studied the distribution of resistance mutations at clonal level, and we analysed the therapeutic strategies used in such cases to achieve undetectable viraemia. The HMDR profile was defined as a genotypic sensitivity score (GSS) ≤1.5 for etravirine and raltegravir with full resistance to darunavir. About 30 clones per gene and per patient were sequenced. Virtual phenotypes were determined. Efficacy of therapeutic strategies was evaluated by follow-up of viral loads, CD4 cell counts and trough concentrations of drugs. Among 1310 patients on treatment and with genotypic resistance testing, 25 (2%) were resistant to darunavir and 11 (0.8%) had an HMDR profile. Five-hundred clones could be analysed for four of them. HMDR profiles were harboured by the great majority of clones and all resistance mutations were located on the same strains for all genes. Despite this and a regimen with a GSS <2.0 in three patients, they achieved a viraemia <20 copies/mL. These results were obtained using different strategies: high doses of drugs; combination of antiretrovirals with full or intermediate susceptibility, such as tipranavir, etravirine or maraviroc; and use of alternative compounds, such as foscarnet or interferon. Patients with HMDR HIV were uncommon, but, in such cases, all resistance mutations were borne on the same majority strains. In this study, tipranavir was the only protease inhibitor with full or intermediate susceptibility. Despite very limited therapeutic options, an undetectable viraemia can be achieved by combining different strategies.
    Journal of Antimicrobial Chemotherapy 07/2013; · 5.34 Impact Factor
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    ABSTRACT: Thirty years after the first descriptions of AIDS in children in May 1983, the risk of viral transmission from mother to child has been reduced to almost zero and the disease in infected children has become an asymptomatic condition, stable in the long-term, thanks to antiretroviral drugs. Unbelievable though it may have seemed until the mid-1990s, children infected during the perinatal period are now growing up to be adults in a chronic, stable, asymptomatic medical condition with often satisfactory personal, family, and social lives. The French perinatal epidemiological cohort, which was set up in 1984 and has included more than 18,000 mother-child pairs to date, traces the steps in this extraordinary revolution in the prevention and treatment of HIV-1 infection in children.
    Archives de Pédiatrie 07/2013; · 0.36 Impact Factor
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    ABSTRACT: Background. Prevention of HIV mother-to-child transmission (PMTCT) is usually based on zidovudine (ZDV)-containing regimens, despite potential toxicities. This multicenter trial evaluated whether lopinavir/ritonavir (LPV/r) monotherapy in HIV-1 infected women not requiring antiretrovirals for themselves could control maternal viral load (VL). Methods. Overall, 105 pregnant women with baseline VL<30000 copies/mL and CD4>350 cells/µL were randomized to start open-label LPV/r 400/100&emsp14;mg bid alone (monotherapy group, n=69) or combined with ZDV/3TC 300/150&emsp14;mg bid (triple therapy group, n= 36) from 26 gestational weeks to delivery. According to a Fleming's two-stage phase II design, monotherapy was considered to be efficacious if at least 59 patients achieved VL <200 copies/mL at 8 weeks of treatment (primary endpoint). Secondary endpoints were VL at delivery and tolerance. Results. Monotherapy was efficacious as defined: 62 women in the monotherapy group achieved VL<200 copies/mL at 34 weeks gestation, i.e. 8 weeks of treatment, (89.9%; 95%CI: 80.2-95.8). At delivery, proportions with VL<200 copies/mL were similar in monotherapy and triple therapy groups (92.8 vs 97.2%; p=0·66), however fewer had VL<50 copies/mL in the monotherapy group (78.3% vs 97.2 %; p=0.01). Changes for intolerance were less frequent in the monotherapy than in the triple therapy group, 1.4% vs 11.1%, respectively (p=0.046). Caesarean section and preterm delivery rates did not differ. All children were liveborn ; one case of HIV transmission occurred in the triple therapy group, none in the monotherapy group (upper 95% CI limit=5.2%). Conclusions. LPV/r monotherapy achieved satisfactory virologic efficacy in women treated solely for PMTCT, providing proof-of-concept for future nucleoside-sparing strategies.
    Clinical Infectious Diseases 06/2013; · 9.37 Impact Factor
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    ABSTRACT: Background. Intrapartum intravenous zidovudine (IV-zidovudine) prophylaxis is a long-standing component of mother-to-child HIV transmission (MTCT) prevention in high-resource countries. In some recent guidelines, IV-zidovudine is no longer systematically recommended for mothers receiving combination antiretroviral therapy (cART) with low viral load. We evaluated the impact of IV-zidovudine according to viral load and obstetrical conditions. Methods. All HIV-1 infected women delivering between January 1, 1997 and December 31, 2010 in the French Perinatal Cohort (ANRS-EPF) were analyzed if they received ART during pregnancy and did not breastfeed. We identified maternal and obstetrical characteristics related to lack of IV-zidovudine and compared its association with MTCT rate and other infant parameters, according to various risk factors. Results. IV-zidovudine was used in 95.2% of the 11,538 deliveries. Older age, multiparity, preterm and vaginal delivery were associated with lack of IV-zidovudine (n = 554). In women who delivered with viral load ≥1000 copies/mL, the overall MTCT rate was higher without than with IV-zidovudine: 7.5% versus 2.9%; p = 0.01. But there was no such difference when the neonate received postnatal intensification therapy. Among them 77% of women who had viral load <400 copies/mL, there is no difference in MTCT rate was respectively: 0% versus 0.6%; p = 0.17. IV-zidovudine was not associated with increased short-term hematological toxicity or lactates level. Conclusions. IV-zidovudine remains an effective tool to reduce transmission in cases of virological failure, even in cART-treated women. However, for the vast majority of women with low viral loads at delivery, in the absence of obstetrical risk factors, systematic IV-zidovudine appears unnecessary.
    Clinical Infectious Diseases 05/2013; · 9.37 Impact Factor
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    ABSTRACT: To evaluate the contribution of CD4 T cells from blood and gut compartments to the HIV-1 reservoir, we directly quantified cell-associated HIV-DNA in isolated rectal (R-) and peripheral blood (PB-) memory CD4 T cells from 11 successfully long-term treated patients. Proportion of activated (CD25;CD69;HLA-DR) and CCR5 expressing CD4 T cells was markedly higher in rectal tissue compared to blood. However, HIV-1 infection levels of R- and PB-memory CD4 T cells did not significantly differ (medians: 4,000 and 2,100 copies/million cells) after effective long-term viral control, suggesting that each of these two compartments does not contribute in a similar fashion to the total HIV reservoir.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 12/2012; · 4.65 Impact Factor
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    ABSTRACT: During 2003-2010, 555 strains isolated from sexually-infected patients at the time of primary HIV-1 infection (PHI) were characterized. Tree topology revealed that 11.7% of PHIs segregated into transmission clusters. CXCR4-usage was identified in 27 strains (4.9%) and was significantly associated with subtype B (p 0.003) and low CD4 cell count (p 0.01). In clustered and unique PHIs, the prevalence of CXCR4-tropic strains was 1.5% and 5.3%, respectively (p 0.35). Our results are in line with the hypothesis of a mucosal bottleneck contributing to the high prevalence of CCR5 variants during PHI.
    Clinical Microbiology and Infection 12/2012; · 4.58 Impact Factor
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    ABSTRACT: OBJECTIVE:: A part of women starting antiretroviral therapy during pregnancy fail to attain undetectable viral load (VL) by delivery. Here we studied whether pregnancy affects the early immunovirological response to cART, taking into account treatment duration and baseline characteristics. DESIGN:: ART-naive women initiating cART since 2004 and followed in 3 French ANRS multicenter HIV cohorts (EPF, PRIMO and COPANA). METHODS:: The early virological response (at 1, 3 and 6 months) and immunological increase after cART initiation were compared between women starting cART during (n = 708) and outside (n = 110) pregnancy. Relative risks were estimated in multivariate models adjusted for treatment duration, baseline VL and CD4, sociodemographic factors and chronic hepatitis B. CD4 increases were compared by using mixed models. RESULTS:: Only 63.8% of treated pregnant women attained a VL <50 copies/mL by delivery. Similarly to nonpregnant women, nearly 90% of pregnant women reached a VL <400 copies/mL at M3 (adjusted RR: 1.0 [95% Confidence Interval 0.7-1.4]), and nearly 100% at M6 following cART initiation (0.9 [0.4-1.9]). VL <50 copies/mL was attained by 61.5% of pregnant versus 67.9% of nonpregnant women at M3 (P = .26), and by 82.1% versus 87.0% at M6 (P = .48). CD4 recovery (both number and percentage) was similar in pregnant and nonpregnant women. Results were similar for the subset of women starting a boosted protease inhibitor-containing cART. CONCLUSIONS:: Pregnancy does not affect the virological response to cART below 400 copies/mL, or CD4 increase. The main reason for pregnant women not achieving VL <50 copies/mL at delivery appears to be a short duration of treatment.
    AIDS (London, England) 10/2012; · 4.91 Impact Factor
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    ABSTRACT: BACKGROUND:: A high prevalence of anal squamous intraepithelial lesions (ASIL) and HPV infections were observed in HIV-infected MSM in the pre-cART (combined antiretroviral therapy) era. The impact of cART on the natural history of HPV infection and ASIL is poorly documented. METHODS:: 94 HIV-infected MSM naïve of cART were enrolled in a longitudinal study before starting cART. Patients were evaluated for anal cytology, histology and anal HPV DNA at baseline, month 12 and month 24 of cART. HPV DNA genotyping was performed by Linear Array assay. Anal cytologic samples were processed by the Thin Prep™ method. RESULTS:: Analyses included 76 patients with at least two visits with available cytology. The median age was 39.4 years. The median (interquartile range) CD4 cell count was 301/mm (242-339) at baseline and 545/mm at month 24, when 93% of patients had plasma HIV-RNA ≤50 copies/ml.Abnormal result was observed in 45 of 76 patients at baseline (59%) with prevalent LSIL in 27 patients (36%) and HSIL in 7 patients (9%) and in 36 of 69 patients assessed at month 24 (52%) with LSIL in 23 patients (33%) and HSIL in 6 patients (9%). At month 24, regression of the severity of lesions was observed in 44% of patients, whereas a lesion occurred in 37% of patients. CONCLUSION:: Our results show a high prevalence and incidence of ASIL in HIV-infected MSM despite immune restoration under cART. These data emphasize that HIV-positive MSM although receiving effective cART remain at high risk of anal SIL.
    AIDS (London, England) 10/2012; · 4.91 Impact Factor
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    ABSTRACT: OBJECTIVES: The genotypic method is reliable enough for the determination of tropism and largely preferred in Europe. However, careful interpretation is essential when assessing HIV genotypic resistance during treatment interruption (TI) due to the possible disappearance of resistant strains. The results of HIV genotypic tropism testing in such a context remain unknown. METHODS: First, we studied changes in tropism in patients included in a structured TI assay: the Reverse study. Second, we investigated the unexpected tropism switches from X4 to R5 recorded in our routine database. RESULTS: Tropism determination was possible in 21 patients of the Reverse study, 9 of whom had an X4 virus (43%) at baseline. Two patients displayed a change of tropism during TI, both switching from X4 to R5. Regarding the database investigation, 7 of the 222 patients with at least two plasma tropism determinations recorded in the database displayed a switch from X4 to R5. TI due to non-compliance at the time of the tropism change was reported for five of these seven patients. CONCLUSIONS: We have shown that the redistribution of the HIV population caused by TI could potentially result in X4 viruses becoming undetected and inappropriate prescription of a CCR5 receptor antagonist. Therefore, genotypic tropism results should be interpreted with caution in such a context.
    Journal of Antimicrobial Chemotherapy 09/2012; · 5.34 Impact Factor

Publication Stats

3k Citations
728.26 Total Impact Points

Institutions

  • 2007–2014
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2007–2013
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service des Maladies Infectieuses et Tropicales
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Institutul Național de Boli Infecțioase "Prof. Dr. Matei Balș"
      Bucureşti, Bucureşti, Romania
  • 2011
    • Hôpital Antoine-Béclère – Hôpitaux universitaires Paris-Sud
      Clamart, Île-de-France, France
  • 2008–2011
    • Assistance Publique – Hôpitaux de Paris
      • Département de Virologie
      Lutetia Parisorum, Île-de-France, France
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2006–2011
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
  • 2000–2001
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France