Lopinavir/ritonavir monotherapy as a nucleoside analogue-sparing strategy to prevent HIV-1 mother-to-child transmission: the ANRS 135 PRIMEVA phase 2/3 randomized trial.

BACKGROUND: Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) is usually based on zidovudine-containing regimens, despite potential toxicities. This multicenter trial evaluated whether lopinavir/ritonavir (LPV/r) monotherapy in HIV type 1-infected women not requiring antiretrovirals for themselves could control maternal viral load (VL). METHODS: Overall, 105 pregnant women with baseline VL <30 000 copies/mL and CD4 ≥350 cells/µL were randomized to start open-label LPV/r 400/100 mg twice daily alone (monotherapy group, n = 69) or combined with zidovudine/lamivudine 300/150 mg twice daily (triple therapy group, n = 36) from 26 gestational weeks to delivery. According to a Fleming 2-stage phase 2 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 (ie, 8 weeks of treatment; 89.9%; 95% confidence interval [CI], 80.2%-95.8%). At delivery, proportions with VL <200 copies/mL were similar in the monotherapy and triple therapy groups (92.8% vs 97.2%; P = .66); however, fewer had VL <50 copies/mL in the monotherapy group (78.3% vs 97.2%; P = .01). Changes for intolerance were less frequent in the monotherapy than in the triple therapy group (1.4% vs 11.1%, respectively; P = .046). Cesarean delivery and preterm delivery rates did not differ. All children were liveborn; 1 case of HIV-1 transmission occurred in the triple therapy group, none in the monotherapy group (95% CI upper 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.

Premature delivery in HIV-infected women starting protease inhibitor therapy during pregnancy: role of the ritonavir boost?

BACKGROUND: The association between combination antiretroviral (cARV) therapy use by human immunodeficiency virus (HIV)-infected women during pregnancy and risk of prematurity is still controversial. We explored this question, focusing on the initiation of ritonavir-boosted protease inhibitors (PIs) during pregnancy, which is now standard care. METHODS: Trends in prematurity (<37 gestational weeks) were studied among all singleton pregnancies in the Agence Nationale de Recherche sur le SIDA (ANRS) French Perinatal Cohort from 1990 through 2009 (n = 13 271). In-depth analysis was conducted in a more detailed substudy of the cohort, among women starting PI-based ARV therapy during pregnancy (n = 1253). Multivariable analysis adjusted for immunovirological status and known risk factors for prematurity. RESULTS: Prematurity increased from 9.2% during 1990-1993 (no therapy) and 9.6% during 1994-1996 (mostly zidovudine monotherapy) to 12.4% during 1997-1999 (dual-nucleoside analog therapy) and 14.3% during 2005-2009 (routine cARV therapy; P < .01). Prematurity was associated with cARV therapy, compared with zidovudine monotherapy, with an adjusted odds ratio of 1.69 (95% confidence interval [CI], 1.38-2.07; P < .01) when accounting for maternal age, intravenous drug use, geographic origin, and CD4 cell count. During 2005-2009, the prematurity rate was higher with boosted than with nonboosted PI therapy started during pregnancy (14.4% vs 9.1% [P = .05]; adjusted hazard ratio, 2.03 [95% CI, 1.06-3.89; P = .03] in multivariate analysis). The difference concerned mainly induced preterm delivery for maternal or fetal indications (5.6% vs 1.6%; P = .02), CONCLUSIONS: The prematurity rate among HIV-infected pregnant women was twice that in the general population in France; this was not entirely explained by sociodemographic characteristics. Prematurity was independently associated with cARV therapy and, particularly, with the initiation of ritonavir-boosted PI therapy during pregnancy.

Amniocentesis and mother-to-child human immunodeficiency virus transmission in the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales French Perinatal Cohort.

OBJECTIVE: The objective of the study was to investigate whether performing an amniocentesis increased mother-to-child transmission of human immunodeficiency virus (HIV)-1 (MTCT). STUDY DESIGN: We studied HIV -1 infected mothers and their children enrolled in the multicenter French Perinatal HIV Cohort from 1985 to 2006. RESULTS: One hundred sixty-six amniocenteses were performed among 9302 singleton pregnancies, the proportion increasing from 1.0% before 2001 to 4.7% in 2005-2006. Use of highly active antiretroviral therapy (HAART) was more frequent in the amniocentesis group (58.4% vs 33.2%). MTCT tended to be higher in the amniocentesis group, among mothers who received no antiretroviral agents (25.0%; 3/12 vs 16.2%; 343/2113; P = .41) as well as among mothers receiving zidovudine monotherapy or a double-nucleoside reverse transcriptase inhibitor combination (6.1%; 3/49 vs 3.3%; 117/3556; P = .22), but the difference was not significant. Among 81 mothers receiving HAART, there was no case of MTCT. CONCLUSION: Our results suggest that amniocentesis is not a major risk factor for mother-to-child transmission in mothers treated with effective antiretroviral therapy.

[Potential value of placental angiogenic factors as biomarkers in preeclampsia for clinical physicians]. / Intérêts potentiels des facteurs angiogéniques placentaires comme biomarqueurs dans la pré-éclampsie pour le clinicien.

The role of angiogenic factors in the onset of clinical manifestations of preeclampsia was demonstrated in 2003 by the implication of sFlt-1, PlGF and VEGF, and in 2006 by the implication of soluble endoglin. Placental ischemia and inflammation observed in preeclampsia alter both the production and progression of angiogenic factors during pregnancy. During the first trimester, the combination of PlGF with clinical, biophysical and biological factors results in a better test than the conventional one. However, the clinical value of this method remains to be confirmed. During the second and third trimesters, the sFlt-1/PlGF ratio may be used, with or without pre-existing renal disease, for short-term prediction, diagnosis, and prognosis, and to evaluate the effectiveness of preeclampsia treatment. While a sFlt-1/PlGF ratio<38 and≤33, respectively, rules out the short-term onset and diagnosis of preeclampsia, a sFlt-1/PlGF ratio≥85 between 20 and 34 weeks of pregnancy and≥110 beyond 34 weeks of pregnancy confirms a diagnosis of preeclampsia. Angiogenic and non-angiogenic preeclampsia are identified by a sFlt-1PlGF≥85 and<85, respectively, with the risk of maternal and fetal complications at two weeks differing between the two. Similarly, a sFlt-1/PlGF ratio>665 and>205, respectively, is a good short-term predictor of adverse outcomes of early and late-onset preeclampsia. These values could be incorporated into future guidelines for better clinical management of preeclampsia.

Amniocentesis in pregnant HIV-infected patients. Absence of mother-to-child viral transmission in a series of selected patients.

OBJECTIVES: To assess the risk of vertical transmission in HIV-infected pregnant women undergoing diagnostic amniocentesis, and to identify possible predictive factors. STUDY DESIGN: This was a single center retrospective study. The records of 330 HIV-infected pregnant women booked in our antenatal clinic from 31 January 2001 to 31 January 2006 were analyzed. Women who actually underwent diagnostic amniocentesis ("amniocentesis performed" group) were compared to those eligible for amniocentesis but who did not undergo the procedure ("amniocentesis withheld" group). RESULTS: During the time period, 318 liveborn babies were delivered (9 HIV infected (2.8%)). Thirty-four women (35 fetuses) were eligible for diagnostic amniocentesis. Amniocentesis was performed in 11 (32.4%) of these women (12 fetuses, none infected among the 9 liveborns) and withheld in 23 (67.6%) women. Among the 19 liveborn babies in this latter group, 1 (5.3%) was infected. There was no statistical difference in vertical transmission rate between the whole cohort of HIV-infected pregnant women and the group of women eligible for amniocentesis; or between the women who actually had or did not have an amniocentesis. The women who did undergo amniocentesis all received highly active antiretroviral combination therapy with three drugs; all but two had an undetectable HIV viral load, only one had immunosuppression and none had HCV co-infection. CONCLUSION: No vertical transmission was observed in a group of nine liveborn babies after amniocentesis performed in selected HIV-infected pregnant women. In the presence of high genetic risk during pregnancy, amniocentesis can be considered after proper patient counselling.