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.
ABSTRACT 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).
To determine whether ART for PMTCT, discontinued after delivery, affects the virological response to highly active antiretroviral therapy (HAART) administered during subsequent pregnancies.
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).
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).
Efficacy of PI-based combinations is not decreased in women previously exposed to various regimens of antiretroviral PMTCT.
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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 mg bid alone (monotherapy group, n=69) or combined with ZDV/3TC 300/150 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; 57(6). DOI:10.1093/cid/cit390 · 9.42 Impact Factor
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ABSTRACT: The dire conditions of the human immunodeficiency virus/acquired immune deficiency syndrome epidemic and the immense benefits of antiretroviral prophylaxis in prevention of mother-to-child transmission far outweigh the potential for adverse effects and undeniably justify the rapid and widespread use of this therapy, despite incomplete safety data. Highly active antiretroviral therapy has now become standard care, and more than half the validated regimens include protease inhibitors. This paper reviews current knowledge of the safety of these drugs during pregnancy, in terms of maternal and fetal outcomes. Transfer of protease inhibitors across the placenta is known to be minimal, and current data about birth defects and fetal malignancies are reassuring. Maternal liver function and glucose metabolism should be monitored in women treated with protease inhibitor-based regimens, but concerns about the development of maternal resistance, should treatment be discontinued, have been shown to be groundless. Neonates should be screened for hematologic abnormalities, although these are rarely severe or permanent and are not usually related to the protease inhibitor component of the antiretroviral combination. Current findings concerning pre-eclampsia and growth restriction are discordant, and further research is needed to address the question of placental vascular complications. The increased risk of preterm birth attributed to protease inhibitors should be interpreted with caution considering the discrepant results and the multitude of confounding factors often overlooked. Although data are thus far reassuring, further research is needed to shed light on unresolved controversies about the safety of protease inhibitors during pregnancy.HIV/AIDS - Research and Palliative Care 09/2013; 5:253-262. DOI:10.2147/HIV.S33058
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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 06/2014; 43(7). DOI:10.1016/j.jgyn.2014.01.006 · 0.62 Impact Factor