JAIDS Journal of Acquired Immune Deficiency Syndromes:
Previous Antiretroviral Therapy for Prevention of Mother-to-Child Transmission of HIV Does not Hamper the Initial Response to PI-Based Multitherapy During Subsequent Pregnancy
Briand, Nelly PhD*; Mandelbrot, Laurent MD*†‡; Blanche, Stéphane MD§‖; Tubiana, Roland MD¶#; Faye, Albert MD†**; Dollfus, Catherine MD††; Le Chenadec, Jérôme MSc*; Benhammou, Valérie PhD*; Rouzioux, Christine PharmD, PhD§‡‡; Warszawski, Josiane MD, PhD*§§‖‖; for the ANRS French Perinatal Cohort (ANRS EPF-CO-01)
From the *CESP INSERM U1018, Equipe VIH et IST Le Kremlin-Bicêtre, France; †Université Paris 7, Paris, France; ‡AP-HP, Hôpital Louis Mourier, Service de Gynécologie et d'obstétrique, Colombes, France; §EA 3620, Univ Paris Descartes 5, Paris, France; ‖AP-HP, Hôpital Necker, Unité d'Immunologie Hématologie Pédiatrique, Paris, France; ¶AP-HP, Hôpital Pitié Salpêtrière, Service de maladies infectieuses, Paris, France; #INSERM, U943, Paris, France; **AP-HP, Hôpital Robert Debré, Service de Pédiatrie Générale, Paris, France; ††AP-HP, Hôpital Trousseau, Service d'Hématologie et d'oncologie pédiatrique, Paris, France; ‡‡AP-HP, Hôpital Necker, Service de Virologie, Paris, France; §§Univ Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France; and ‖‖AP-HP, Hôpital Bicêtre, Service d'Epidemiologie and Santé Publique, Le Kremlin-Bicêtre, France.
Received for publication December 15, 2010; accepted March 9, 2011.
Supported by the Agence Nationale de Recherche sur le SIDA et les Hépatites virales (ANRS). Sidaction awarded a scholarship to N.B.
A part of the results were presented as poster at the 17th Conference on Retrovirus and Opportunistic Infections, in February 2010 in San Francisco, CA.
The author N.B. performed the statistical analysis and contributed to the design of the study, data interpretation, and the writing of this article. J.W. is the principal investigator of the ANRS CO-01 EPF and was responsible for the whole scientific process of this study. All of the authors contributed significantly to article and approved the final version.
The authors have no conflict of interest to declare.
The people and institutions participating in the ANRS French Perinatal Cohort (EPF) are listed in the Appendix I.
Correspondence to: Nelly Briand, PhD, Equipe VIH et IST, CESP, INSERM U1018, 82 rue du Général Leclerc, 94276 Le Kremlin Bicêtre cedex, France (e-mail: firstname.lastname@example.org).
Background: Few data are available on the possible long-term negative effects of a short exposure to antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT).
Objective: To determine whether ART for PMTCT, discontinued after delivery, affects the virological response to highly active antiretroviral therapy (HAART) administered during subsequent pregnancies.
Methods: All current pregnancies of HIV-1-infected women enrolled in the French Perinatal Cohort (ANRS CO-01 EPF) between 2005 and 2009 and not receiving ART at the time of conception were eligible. We studied the association between history of exposure to ART during a previous pregnancy and detectable viral load (VL) under multitherapy at current delivery (VL ≥ 50 copies/mL).
Results: Among 1116 eligible women, 869 were ART naive and 247 had received PMTCT during a previous pregnancy. Previous ART was protease inhibitor (PI)-based HAART in 48%, non-PI-based HAART in 4%, nucleoside reverse transcriptase inhibitor bitherapy in 19% and zidovudine monotherapy in 29% of the women. At current pregnancy, women with or without prior exposure to ART had similar CD4 cell counts and VL before ART initiation. PI-based HAART was initiated in 90% of the women. VL was undetectable (<50 copies/mL) at delivery in 65% of previously ART-naive women, 72% of women previously exposed to HAART, 62% previously exposed to bitherapy, and 67% previously exposed to monotherapy for prophylaxis (P = 0.42). Detectable VL was not associated with previous exposure in multivariate analysis (adjusted OR for previous versus no previous exposure to ART: 0.92; 0.95% confidence interval: 0.59 to 1.44).
Conclusions: Efficacy of PI-based combinations is not decreased in women previously exposed to various regimens of antiretroviral PMTCT.
A spectacular decrease in mother-to-child transmission of HIV-1 has been obtained in industrialized countries, with the widespread use of antiretroviral therapies (ARTs) reducing transmission rates to about 1%-2%.1-6 For women who do not require long-term ART for their own health, the standard regimen for prevention of mother-to-child transmission (PMTCT) has progressively changed from zidovudine monotherapy in 19947 to nucleoside reverse transcriptase inhibitor (NRTI) bitherapy2 and then to highly active antiretroviral therapy (HAART).8-11 The most recent guidelines suggest that ART should be discontinued after delivery if indicated solely for the PMTCT.8,10,11 Little is known about the possible long-term negative effects of this strategy of a short period of exposure to ART, particularly as concerns the virological response to subsequent HAART administered for clinical or immunovirological indications. A poorer 6-month virological response to nevirapine-based regimens has been reported in women previously exposed to single-dose nevirapine for PMTCT in Bostwana and Thailand associated with nevirapine resistance.12-14 Mutations conferring resistance to lamivudine acquired during short-term exposure for PMTCT were shown to be associated with subsequent virological failure in a study in the Ivory Coast evaluating the maternal 12-month response to lamivudine-based multitherapy.15 Immunological response was not associated with resistance to nevirapine or lamivudine15 or with previous exposure to nevirapine.16 One matter of concern is that treatment interruptions during ART randomized in Strategies for Management of Anti-Retroviral Therapy (SMART) trial were shown to have a negative impact on outcome.17,18 However, the patients enrolled in SMART were treated for clinical or biological signs of immunodepression, mostly low CD4 lymphocyte counts. Few data are available concerning the response to PI-based HAART after previous short periods of exposure to ART for PMTCT.
We studied here short-term virological and immunological responses to HAART initiated during pregnancy in women who had received ART prophylaxis for a previous pregnancy and in women who had never before received ART. We used data from the ANRS French Perinatal Cohort (ANRS CO-01 EPF), in which almost one-third of all pregnant HIV-positive women were enrolled at least twice, most receiving PI-based HAART during their most recent pregnancy between 2005 and 2009.
The ANRS French Perinatal Cohort
Since 1985, the ANRS French Perinatal Cohort (ANRS CO01 EPF) has prospectively enrolled HIV-infected women giving birth at 90 centers throughout France. The methodology used has been described elsewhere.5 Informed consent was obtained from all mothers. No specific recommendation for HIV treatment and obstetric care was made for women included in the cohort. French national guidelines for PMTCT are published and updated regularly.8 This cohort study was approved by the institutional review board of Cochin Hospital and the French computer database watchdog (Commission Nationale de l'Informatique et des Libertés).
Between 1985 and 2009, we enrolled 9323 HIV-infected women in the ANRS CO01 EPF, 2605 of whom had had 2 or more pregnancies. Between 2005 and 2009, 3021 pregnancies were enrolled, 1589 of these women initiated ART during pregnancy, having not already been receiving treatment at the time of conception.
We defined 3 groups for this analysis, according to previous exposure to ART and time of HIV diagnosis as follows: (1) women diagnosed with HIV during this current pregnancy, who had never received ART before the pregnancy (group 1A); (2) women diagnosed with HIV before this pregnancy but never treated before (group 1B); (3) women exposed to ART only during the last (previous) pregnancy, with treatment stopped after delivery (group 2). The 2 first groups (G1A and G1B) are referred to as “ART naive”. The third group (G2) was considered “previously exposed to ART for PMTCT”. We then excluded the small number of women who had received ART for PMTCT in more than 1 previous pregnancy (n = 45), mothers who had previously received ART in situations other than a pregnancy (n = 425), and 3 women for whom data were missing concerning the time of HIV diagnosis.
We used obstetric and HIV treatment data recorded for the current pregnancy as follows: age, geographic origin, gestational age at booking maternity, type of ART and time of treatment initiation and cessation, gestational age at and mode of delivery (vaginal, emergency cesarean section, or elective cesarean section), all CD4 cell counts and percentages, and plasma HIV-1 RNA viral loads during pregnancy and close to the time of delivery (not more than 7 days after delivery). Gestational age was determined from the date of the last menstrual period, corrected when appropriate by the date of conception as evaluated from the early ultrasound. Baseline characteristics were the first data collected during pregnancy, even if they were available before booking maternity: this data included, in particular, pretherapeutic immunovirological status and gestational age at ART initiation and type of ART when prescribed by HIV specialist soon after conception.
Antiretroviral exposure during the previous pregnancy was categorized into 4 groups according to the largest number of drugs administered simultaneously as follows: NRTI monotherapy, NRTI bitherapy, PI-based HAART, and non-PI-based HAART.
We first compared the baseline characteristics between the group 1A (“ART-naive” women, diagnosed with HIV infection during this pregnancy) and group 1B (“ART-naive” women, diagnosed with HIV infection before this pregnancy). We then compared the group 1B with the group 2 (women “previously exposed to ART for PMTCT”), as these women were unlikely to have required antiretroviral therapy for themselves because they were not receiving ART at the time of conception, despite their HIV infection being known. We restricted most analyses to women given PI-based HAART during the current pregnancy who accounted for 90% of cases.
We then described changes in log10 viral load, CD4 cell count and percentage during pregnancy, according to the presence or absence of prior exposure to ART, using locally versus weighted regression (lowest), estimated with R software. We then studied the association between no or previous exposure to ART and detectable viral load (≥ 50 copies/mL) close to the time of delivery in univariate and multivariate analysis.
We used χ2 or Fisher exact tests to compare percentages and Student t tests or Wilcoxon rank tests to compare continuous variables in univariate analysis. Logistic regression was used for multivariate analysis, adjusting for CD4 cell count before ART initiation and noncollinear variables found to be associated with detectable viral load with a univariate P value <0.20. Analyses were conducted with SAS statistical software (version 9.1; SAS, Institute Inc, Cary, NC). The P < 0.05 was used to define statistical significance.
At the onset of the current pregnancy, 869 women were “ART naive” (522 diagnosed with HIV infection during this pregnancy and 347 diagnosed before this pregnancy) and 247 women had previously been exposed to ART for PMTCT. The ART initiated during the current pregnancy was PI-based HAART in 90.3% of the women, non-PI-based in 1.4%, NRTI bitherapy in 6.3%, and NRTI (zidovudine) monotherapy in 2.1% of the women. We excluded women not receiving PI-based HAART during the current pregnancy from subsequent analysis.
Characteristics Before PI-Based HAART Initiation During the Current Pregnancy
Group 2 (women “previously exposed to ART for PMTCT”) and group 1B (women “ART naive” despite the diagnosis of HIV infection before the current pregnancy) had similar initial characteristics, except that the women in group 1B were younger and booked earlier (Table 1). As expected, the women of group 1A (women “ART naive” and diagnosed with HIV infection during the current pregnancy) were more likely to have originated from sub-Saharan Africa, booked later, to have begun ART later and to have a lower median CD4 cell count and higher median viral load before starting ART than the women in group 1B (Table 1). No differences were observed between the 3 groups in terms of the duration of ART and the type of PI used during pregnancy (71.2% received boosted lopinavir and 15.7% nelfinavir) (Table 1), gestational age at delivery, and mode of delivery (Table 2). Only 13% (130 of 1007) of women changed ART regimen during the pregnancy, mostly for reasons of tolerance; the proportions of such cases were similar in the 3 groups.
The women previously exposed to ART for PMTCT had received HAART in 52.1% of cases, mostly PI based (93.0%), NRTI bitherapy in 19.2% and NRTI (zidovudine) monotherapy in 28.8% (Table 1).
Immunological Response After PI-Based HAART Initiation During the Current Pregnancy
The women of group 1B (ART naive diagnosed before the pregnancy) had CD4 cell counts at delivery higher than those of the women of group 1A (diagnosed during the pregnancy), but similar to those of the women of group 2 (previously exposed to ART) (Table 2). The women of group 2 and the total ART-naive group (group 1) had similar categorical and median CD4 cell counts and percentages at delivery, with similar trends during pregnancy (Fig. 1A), whenever HIV was diagnosed and whatever the type of previous ART (Fig. 1B).
Virological Response After PI-Based HAART Initiation During the Current Pregnancy
The proportion of women with an undetectable viral load (below 50 copies/mL) close to delivery was similar for ART-naive women and women previously exposed to PMTCT as follows: 68.7% in group 2 versus 64.6% in group 1, P = 0.26. No differences were observed either for the proportions of women with viral loads below 200 copies per milliliter (85.3% vs. 86.3%, respectively; P = 0.70). The proportion of women with viral loads above 10,000 copies per milliliter was 2.3% for group 2 and 1.0% for group 1. The maternal viral load curves during pregnancy were similar for ART-naive and ART-exposed women (Fig. 2A), whenever HIV was diagnosed and whatever the type of previous ART (Fig. 2B).
The proportion of women with detectable VL (≥50 copies/mL) was similar for women who were ART naive at the time of conception (35.4%; 279 of 788) and those previously exposed to PI-based HAART (27.9%; 29 of 104), previously exposed to non-PI-based HAART (25.0%; 2 of 8) or previously exposed to NRTI monotherapy (33.3%; 21 of 63). This proportion tended to be higher in women previously exposed to NRTI bitherapy (38.1%; 16 of 42), but not significantly so (Table 3). The median time interval between treatment initiation during pregnancy and time of viral load measurement was 12.6 weeks (interquartile range: 8.9-17.1).
Detectable viral load was associated with unknowledge of HIV seropositivity before pregnancy, late gestational age at booking, late time at initiation of the first line of treatment, higher level of viral load before ART initiation, and severe prematurity (gestational age < 33 weeks). After adjustment for these factors and for maternal age and CD4 cell count before ART, previous exposures to ART for PMTCT remained not related to a detectable viral load at delivery (Table 3). Overall adjusted odds ratio for women previously exposed to PMTCT versus ART-naive women was 0.92 (95% confidence interval: 0.59 to 1.44, P = 0.72).
In women previously exposed to PMTCT, viral load at delivery was lower in the current pregnancy than in the previous pregnancy (89.9% vs. 74.8% < 400 copies/mL). However, it was similar in the 2 pregnancies for women who received PI-based HAART in both pregnancies. The median time between the last pregnancy and the current pregnancy was 28.1 months (interquartile range: 16.9-47.3). The time between pregnancies was not associated with the risk of obtaining a detectable viral load in the current pregnancy (Table 3).
The French Perinatal Cohort study (ANRS EPF-CO-01) did not record follow-up after delivery, except during the subsequent pregnancy for women re-enrolled at this occasion. This situation, which concerned one-third of women, provided us with a unique opportunity to investigate, in a large sample, the effects of prior exposure to PMTCT on the immunological and viral response to subsequent PI-based HAART. Increasing numbers of HIV-infected women are having several children, as a consequence of improvements in the prognosis of HIV infection and the reduction of mother-to-child transmission.19-21 Repeat pregnancies now account for one-third of the mother-child pairs enrolled in the EPF, which covers an estimated 70% of HIV-infected mothers giving birth each year in France.
Our findings show that the virological response to PI-based HAART in pregnancy did not differ between women who were ART naive and women previously exposed to ART for PMTCT. Plasma viral load at delivery was below 200 copies per milliliter in almost 86% of women in both groups and was undetectable (<50 copies/mL) in 64.6% of ART-naive women and 68.7% of those previously exposed to ART. Our study had a 80% power with a 2-tailed significance level of 5% to show an odds ratio associated with increasing risk of detectable viral load in women previously treated for PMTCT of 1.6 and 99% power to show an odds ratio of 2.0.
The lack of difference in viral load response between women with and without prior exposure to PMTCT could not be accounted for by any difference in gestational age at ART initiation or duration of ART during pregnancy, type of PI used or proportion of changes in ART during pregnancy. The proportion of women with low viral loads by the time of delivery was similar to those reported in various European studies of women receiving HAART who were ART naive before the pregnancy. In the Swiss HIV Cohort Study, 93% of women had a viral load below 400 copies per milliliter at delivery22; in the European Collaborative Study, 73% reached an undetectable viral load23 and, in an Italian study, 66% of women enrolled between 2005 and 2008 had viral load below 50 copies per milliliter during the third trimester.24
The initial characteristics of the women who were ART naive at the onset of pregnancy differed between those who discovered their HIV-positive status during the pregnancy and those who already knew their HIV status. As expected, women aware of their HIV status but not yet receiving ART had better initial immunovirological markers, as most did not require ART for their own health. This subgroup of women did not differ from women who received ART for PMTCT in a previous pregnancy, with this treatment stopped after delivery. The 3 groups were similar in terms of the gestational age at which ART was started and the type of PI used. Similar proportions of women in each group had undetectable viral loads at delivery. Taking the time at diagnosis into account for these women did not affect our findings for virological response after the initiation of PI-based HAART. Immunological reconstitution was also similar in ART-naive women and women previously exposed to ART.
HAART has been recommended for almost all HIV-1-infected pregnant women since 2005.8 Most previous studies on the impact of PMTCT on subsequent response to ART concerned the response to nevirapine-based regimens after prior exposure to single-dose nevirapine for PMTCT, which is associated with the development of resistance.12,13,16 In France, as in other industrialized countries, single-dose nevirapine at delivery is not recommended, and the standard treatment is PI-based HAART.8 To our knowledge, this is the first study to focus on the response to PI-based HAART after previous exposure to ART exclusively for PMTCT. The PI used was ritonavir-boosted lopinavir in two-thirds of cases. Katz et al25 reported a relationship between virological failure in pregnant women receiving mostly PI-based HAART and a self-reported history of HAART before pregnancy, but the type and duration of previous exposure to HAART was not detailed.
Different types of ART were administered during the previous pregnancy as follows: NRTI monotherapy, NRTI bitherapy, non-PI-based HAART, and PI-based HAART. The proportion of women treated with PI-based HAART during the current pregnancy for whom VL was undetectable did not depend on the previous type of exposure. However, it tended to be lower in mothers exposed to NRTI bitherapy, consisting of zidovudine-lamivudine in all cases (except 1 woman previously treated with zidovudine plus didanosine). Nevertheless, the number of mothers in this subgroup (n = 42) was small and consequently the statistical power to show an odds ratio of 1.6 associated with this subgroup compared with naive women was only 54%. Coffie et al15 reported resistance mutations in 15% of women exposed to lamivudine for PMTCT, tested 4 weeks after delivery, in Abidjan, Ivory Coast. In 50% of these women, viral load was not held below 500 copies per milliliter 12 months after the initiation of lamivudine-containing HAART with nevirapine or efavirenz. Data on resistance mutations were not routinely collected in the EPF cohort. The proportion of patients previously exposed to NRTI bitherapy and treated with PI-based HAART during the current pregnancy for whom virological success was recorded was much higher than in the African study as follows: 87% had a viral load below 500 copies per milliliter after a median of 3 months of treatment. This proportion remained high in women who received PI-based HAART containing lamivudine: 90%.
For patients exposed to PI-based HAART in the last pregnancy, the proportion of viral suppression at delivery under PI-based HAART for the current pregnancy (72% < 50 copies/mL) was as high as that for the ART-naive group. This is consistent with the higher genetic barrier for the development of resistance to PI26-33 than for the development of resistance to nevirapine and lamivudine. In previous reports, the prevalence of nevirapine mutations decreased over time and the proportion of women presenting virological failure decreased with increasing time between PMTCT exposure and HAART initiation.12,13 We found no relationship between the timing of treatment with respect to previous ART exposure and viral load response in women treated with PI-based HAART in the current pregnancy.
One limitation of this study is that it concerned only the short-term response to PI-based HAART, until delivery, a median of 3 months after treatment initiation. In women who start treatment for low CD4 counts, a weaker response to HAART after 3 months than observed here would be expected, even if the response did not differ between women with and without prior exposure. We did not routinely collect resistance data in the EPF cohort, but this seems to be only a minor limitation of this study because the viral response did not differ between the groups compared.
The main strength of our study is that it is the first, as far as we are aware, to evaluate responses to PI-based HAART in women previously exposed to ART exclusively for PMTCT. The sizes of the samples of ART-naive women and women previously exposed for PMTCT in this cohort were large enough to obtain a sufficient statistical power.
In conclusion, our findings strongly suggest that exposure to HAART for PMTCT stopped after delivery has no negative impact on the response to PI-based HAART during subsequent pregnancy. We can infer that such exposure should not reduce the response to PI-based HAART subsequently initiated for maternal health indications.
We thank all mothers who agreed to participate in this study. We thank Linda Assoul, Naïma Bouallag, Leila Boufassa, Nacima Chernai, Sandrine Delmas, Karima Hamrène, Paulette Huynh, Carine Jasseron, Nadia Kessaci, Corinne Laurent, Jacques Ngondi Ekome, Marlène Péres, Elisa Ramos, Jean-Paul Teglas, and Thierry Wack.
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APPENDIX I: PEOPLE AND INSTITUTIONS PARTICIPATED IN ANRS FRENCH PERINATAL COHORT
The following people and institutions participated in the ANRS French Perinatal Cohort:
Hôpital Nord, Amiens (Decaux N, Douadi Y, Gondry J, Li Thiao Te V, Schmit J. L); Hôpital d'Angers (Fournié A); Hôpital Victor Dupouy, Argenteuil (Allisy C, Brault D); Hôpital Robert Ballanger, Aulnay (Questiaux E, Zakaria A, Goldenstein C); Hôpital de Bastia (Pincemaille O); Hôpital de la Côte Basque, Bayonne (Bonnal F, Cayla C, Hernandorena X); Hôpital Saint Jacques, Besançon (Estavoyer J. M, Maillet R); Hôpital Avicenne, Bobigny (Bentata M); Hôpital Jean Verdier, Bondy (Benoist L, Bolie S, Bonier N, Lachassine E, Rodrigues A); Hôpital Pellegrin, Bordeaux (Douard D, Roux D, Schaeffer V); Hôpital Clémenceau, Caen (Beucher G, Brouard J, Goubin P); Hôpital André Rosemon, Cayenne (Elenga N); Hôpital de Creil (Carpentier B, Duval-Arnould M, Kingue-Ekollo C); Hôpital Intercommunal, Créteil (Garrait V, Lemerle S, Pichon C, Richier C, Touboul C); Hôpital Béclère, Clamart (Bornarel D, Chambrin V, Clech L, Foix L'Hélias L, Labrune P, Schoen H); Hôpital Louis Mourier, Colombes (Crenn-Hebert C, Floch-Tudal C, Mazy F, Hery E, Meier C); Hôpital d'enfants, Dijon (Martha S, Reynaud I); Hôpital Intercommunal, Evreux (Allouche C, Touré K); Hôpital Francilien Sud, Evry-Corbeil (Chevojon P, Devidas A, Granier M, Marchand C, May A, Nguyen R, Turpault I); Hôpital de Fontainebleau (Alissa K, Routier C); Hôpital Victor Fouche, Fort de France (Hatchuel Y, William C); Hôpital de Lagny (Chalvon Demersay A, Froguel E, Gourdel B, Lanty C); Hôpital Les Oudairies, La Roche sur Yon (Aubry O, Brossier J. P, Esnault J. L, Leautez S, Perré P, Suaud I); Hôpital de La Seyne sur Mer (Chamouilli J. M); Hôpital André Mignot, Le Chesnay (Hentgen V, Messaoudi F); Hôpital de Bicêtre, Le Kremlin-Bicêtre (Fourcade C; Fridman S; Peretti D); Hôpital Jeanne de Flandres, Lille (D'angelo S, Hammou Y, Mazingue F); Hôpital de Longjumeau (Bailly-Salin P, Turpault I, Seaume H); Hôpital Hôtel Dieu-Institut d'hématologie-oncologie pédiatrique, Lyon (Bertrand Y, Brochier C; Cotte L, Kebaïli K, Tache N, Roussouly M. J, Thoirain V); Hôpital François Quesnay, Mantes La Jolie (Delanete A, Doumet A, Granier F, Salomon J. L); Hôpital la Conception, Marseille (Cravello L); Hôpital La Timone Marseille (Thuret I); Hôpital de Meaux (Karaoui L, Lefèvre V); Hôpital Marc Jacquet, Melun (Le Lorier B); Hôpital Intercommunal, Montfermeil (Dehlinger M, Echard M, Mullard C, Talon P); Hôpital Arnaud de Villeneuve, Montpellier (Benos P, Guigue N, Lalande M); Hôpital Intercommunal, Montreuil (Heller-Roussin B, Riehl C, Winter C); Maternité Régionale A. Pinard, Nancy (Hubert C); Hôpital de Nantes (Brunet-François C, Mechinaud, Reliquet, V), Hôpital l'Archet-Fondation Lenval, Nice (Bongain A, Deville A, Galiba E, Monpoux F); Hôpital Caremeau, Nîmes (Dendale-Nguyen J); Hôpital Orléans (Arsac P, Werner E); Hôpital d'Orsay (Chanzy S, De Gennes C, Isart V); Hôpital Bichat, Paris (Bastian H. Bourgeois-Moine A, Matheron S, Rajguru R); Hôpital Cochin-Port Royal, Paris (Boudjoudi N, Firtion G, Fouchet M, Goupil I, Pannier A); Hôpital Lariboisière, Paris (Ayral D, Ciraru-Vigneron N, Mouchnino G); Hôpital Necker, Paris (Boucly S, Blanche S, Maignan A, Parat S, Rouzioux C, Viard J., Yamgnane A, Cayol V); Hôpital Pitié Salpêtrière, Paris (Bonmarchand M, De Montgolfier I, Quetin F, Edeb N, Lemercier D, Harif M, Marcel S, Pauchard M, Tubiana R); Hôpital Robert Debré, Paris (Faye A, Garion D, Leveille S; Levine M, Ottenwalter A, Recoules A); Hôpital Saint-Antoine, Paris (Bui E, Carbonne B, Meyohas M. C, Rodriguez J); Hôpital Hôpital Saint Michel, Paris (Aufrant C); Hôpital Tenon, Paris (Hervé F, Lebrette M. G); Hôpital Trousseau, Paris (Dollfus C, Tabone M. D, Vaudre G, Wallet A); Hôpital Marechal Joffre, Perpignan (Bachelard G, Medus M); Hôpital Les Abymes, Pointe-à-Pitre (Bataille H); Hôpital René Dubos, Pontoise (Coursol A); Hôpital Américain, Reims (Munzer M); Hôpital Charles Nicolle, Rouen (Brossard V); Hôpital de Saint-Denis (Allemon M. C, Bolot P, Ekoukou D, Ghibaudo N, Gyardeau S, Khuong M. A); Hôpital Nord, Saint Etienne (Billiemaz K); Hôpital de Saint Martin (Bissuel F, Walter V); Hôpital de Haute Pierre-Hôpital Civil, Strasbourg (Cheneau M, Entz-Werle N, Favreau J, Partisani M); Hôpital Chalucet, Toulon (Hittinger G); Hôpital Paule de Viguier, Toulouse (Antras M, Armand E, Berrebi A, Tricoire J) Hôpital Bretonneau, Tours (Besnier J. M, Nau P); Hôpital Brabois, Vandoeuvre les Nancy (Neimann L); Hôpital de Villeneuve Saint Georges (Chacé A, Guillot F, Matheron I). Cited Here...
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Clinical Infectious DiseasesLopinavir/Ritonavir Monotherapy as a Nucleoside Analogue-Sparing Strategy to Prevent HIV-1 Mother-to-Child Transmission: The ANRS 135 PRIMEVA Phase 2/3 Randomized TrialClinical Infectious Diseases
antiretroviral drugs; epidemiology; HAART; HIV; MTCT
© 2011 Lippincott Williams & Wilkins, Inc.
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