Maternal 12-Month Response to Antiretroviral Therapy following Prevention of Mother-to-Child Transmission of HIV Type 1, Ivory Coast, 2003- 2006

Coffie, Patrick A.; Ekouévi, Didier K.; Chaix, Marie‐Laure; Tonwe-Gold, Besigin; Amani-Bossé, Clarisse; Becquet, Renaud; Viho, Ida; dri-Yoman, Thérèse Nʼ; Leroy, Valériane; Abrams, Elaine J.; Rouzioux, Christine; Dabis, F.

doi:10.1086/526780

Cited by 47 publications

(41 citation statements)

References 29 publications

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“…To prevent MTCT of HIV at about the time of delivery, a single dose of nevirapine (sdNVP) is administered at the start of labor and is the most common antiretroviral regimen used in resource-limited settings, as recommended by the World Health Organization (http://www.who.int/hiv/pub/mtct/en/arvdrugswomenguidelinesfinal .pdf). However, the use of sdNVP results in resistance mutations in 15 to 70% of women at 4 to 6 weeks postpartum (2,10,14), compromising the success of subsequent treatments with NVP in mother and child (7,19,15). The results of a recent clinical trial suggest that adding a single dose of tenofovir (TDF) and emtricitabine (FTC) at delivery may reduce those resistance rates by half (6).…”

mentioning

confidence: 99%

Population Pharmacokinetics of Nevirapine in HIV-1-Infected Pregnant Women and Their Neonates

Benaboud

Ekouévi

Urien

et al. 2011

Antimicrob Agents Chemother

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The aim of the present study was to describe the nevirapine (NVP) pharmacokinetics (PK) in pregnant women and their neonates and to evaluate the transplacental drug transfer and administration scheme for the prevention of mother-to-child transmission. Thirty-eight HIV-1-infected pregnant women were administered one tablet of NVP (200 mg) and two tablets of tenofovir-emtricitabine (Truvada) at the initiation of labor. Children were given NVP syrup (2 mg/kg of body weight) as a single dose (sdNVP) on the first day of life. By pair, NVP concentrations were measured in 11 maternal, 1 cord blood, and 2 neonatal plasma samples and analyzed by a population approach. A one-compartment model was used for mothers and neonates; the absorption rate constants for mothers and neonates were 0.95 h ؊1 (intersubject variability, 111%) and 0.39 h ؊1 , respectively; the apparent elimination clearances were 1.42 liter ⅐ h ؊1 (intersubject variability, 22%) and 0.035 liter ⅐ h ؊1 , respectively; and apparent volumes of distribution were 87.3 liters (intersubject variability, 25%) and 5.65 liters, respectively. An effect compartment was linked to maternal circulation by mother-to-cord and cord-to-mother rate constants of 1.10 h ؊1 and 1.43 h ؊1 , respectively. Placental transfer, expressed as the fetal-to-maternal area under the curve ratio, was 75%. Neonates had a very long half-lives (110 h) compared to adults. In the 38 mothers, the simulated median individual predicted time during which the NVP concentration remained above the half-maximal inhibitory concentration (IC 50 ) was 13.2 days (range, 12 to 19.2 days). Thus, the administration of tenofovir-emtricitabine for at least 3 weeks after delivery should be considered to prevent the emergence of resistant viruses. The neonate must receive sdNVP immediately after birth when the infant is born less than 30 min after maternal drug intake to keep NVP concentrations above the IC 50 .Mother-to-child transmission (MTCT) accounts for 20% of all new HIV infections in sub-Saharan Africa (http://data.unaids.org /pub/Report/2009/2009_epidemic_update_en.pdf.). To prevent MTCT of HIV at about the time of delivery, a single dose of nevirapine (sdNVP) is administered at the start of labor and is the most common antiretroviral regimen used in resource-limited settings, as recommended by the World Health Organization (http://www.who.int/hiv/pub/mtct/en/arvdrugswomenguidelinesfinal .pdf). However, the use of sdNVP results in resistance mutations in 15 to 70% of women at 4 to 6 weeks postpartum (2,10,14), compromising the success of subsequent treatments with NVP in mother and child (7,19,15). The results of a recent clinical trial suggest that adding a single dose of tenofovir (TDF) and emtricitabine (FTC) at delivery may reduce those resistance rates by half (6).Nevirapine is characterized by rapid and nearly complete absorption, rapid distribution throughout the body, metabolism by the hepatic cytochrome P450 (CYP) 3A4 (CYP 3A4) enzyme (with autoinduction during the first 2 weeks of treatment), ...

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confidence: 99%

Population Pharmacokinetics of Nevirapine in HIV-1-Infected Pregnant Women and Their Neonates

Benaboud

Ekouévi

Urien

et al. 2011

Antimicrob Agents Chemother

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“…HIV-DNA level was also predictive of progression to immunodefi ciency when measured at the time of primary infection [ 8 ]. The high predictive value for disease progression results was also observed in a cohort of African patients [ 9 ]. In all studies, HIV-DNA levels were positively correlated to HIV-RNA and negatively to CD4 T cell count.…”

Section: Introductionmentioning

confidence: 58%

Quantification of Total HIV1-DNA in Peripheral Blood Mononuclear Cells

Rouzioux

Mélard

Avettand-Fènoël

2014

Methods in Molecular Biology

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HIV reservoir measurement in patients is one of the challenges at the time of testing new treatment approaches aiming at eradicating HIV infection. HIV reservoirs are complex and disseminated in a large number of organs and lymphoid tissues. We chose to quantify total cell-associated HIV-DNA in PBMC as a marker of HIV reservoirs and described the method we developed. The marker was used in large cohort studies at different stages of HIV disease and in therapeutical trials. Our results show how informative is this marker, as well as that plasma HIV-RNA and CD4 T cell count are representative of each patient when measured in blood. Such a series of results might help to adapt simplification or structured interruption strategies, design new clinical trials targeting HIV reservoirs, and select populations that could benefit of such new treatments.

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“…Previous studies reported that a single dose of NVP can already select drug-resistant viral strains in HIV-1-infected mothers (17,22), compromising subsequent maternal treatment success (8,25,29) and potentially promoting the transmission of NVP-resistant strains to the child during subsequent breastfeeding. We wanted to assess predictors for the selection of drug-resistant strains in HIV-1 infected mothers, which might subsequently lead to the transmission of resistant virus to the breastfed child.…”

Section: Resultsmentioning

confidence: 99%

“…However, the exact mechanism of HIV-1 prevention by NVP during intrapartum transmission remains unknown. Furthermore, owing to its long half-life, NVP frequently selects drug-resistant viral strains in HIVinfected mothers (17,22), which can compromise the efficacy of follow-up maternal and newborn antiretroviral treatment (ART) (8,25,29,39).…”

mentioning

confidence: 99%

Quantifying the Impact of Nevirapine-Based Prophylaxis Strategies To Prevent Mother-to-Child Transmission of HIV-1: a Combined Pharmacokinetic, Pharmacodynamic, and Viral Dynamic Analysis To Predict Clinical Outcomes

Frank

Kleist

Kunz

et al. 2011

Antimicrob Agents Chemother

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Single-dose nevirapine (sd-NVP) and extended NVP prophylaxis are widely used in resource-constrained settings to prevent vertical HIV-1 transmission. We assessed the pharmacokinetics of sd-NVP in 62 HIV-1-positive pregnant Ugandan woman and their newborns who were receiving sd-NVP prophylaxis to prevent mother-to-child HIV-1 transmission. Based on these data, we developed a mathematical model system to quantify the impact of different sd-NVP regimens at delivery and of extended infant NVP prophylaxis (

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Maternal 12-Month Response to Antiretroviral Therapy following Prevention of Mother-to-Child Transmission of HIV Type 1, Ivory Coast, 2003- 2006

Abstract: Our study found that poor adherence and 3TC resistance acquired after the intervention to prevent mother-to-child transmission of HIV infection were associated with virologic failure in women who initiated antiretroviral treatment.

Cited by 47 publications

References 29 publications

Population Pharmacokinetics of Nevirapine in HIV-1-Infected Pregnant Women and Their Neonates

Population Pharmacokinetics of Nevirapine in HIV-1-Infected Pregnant Women and Their Neonates

Quantification of Total HIV1-DNA in Peripheral Blood Mononuclear Cells

Quantifying the Impact of Nevirapine-Based Prophylaxis Strategies To Prevent Mother-to-Child Transmission of HIV-1: a Combined Pharmacokinetic, Pharmacodynamic, and Viral Dynamic Analysis To Predict Clinical Outcomes

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