Successful use of darunavir, etravirine, enfuvirtide and tenofovir/emtricitabine in pregnant woman with multiclass HIV resistance

Furco, André; Gosrani, Bhairvi; Nicholas, Sara; Williams, Amanda; Braithwaite, Wunmi; Pozniak, Anton; Taylor, Graham P.; Asboe, David; Lyall, Hermione; Shaw, Andrew J.; Kapembwa, Moses

doi:10.1097/qad.0b013e32832027d6

Cited by 37 publications

(22 citation statements)

References 10 publications

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“…36 Furco et al described a 38-yearold woman with multidrug-resistant HIV and pregnant with a twin gestation who received etravirine 200 mg twice daily beginning at 25 weeks' gestation in combination with darunavir, ritonavir, and enfuviritide. 38 Her HIV RNA viral load improved from 4,660 copies/mL to ,50 copies/mL, while her CD4 count decreased from 471 cells/µL to 356 cells/µL. Etravirine trough levels were 896 ng/mL (etravirine trough values in adults have been reported to range from 192 ng/mL to 297 ng/mL) with a peak level of 1,210 ng/mL 6 hours after the dose.…”

Section: Etravirine In Pregnancymentioning

confidence: 95%

“…Paired maternal-cord blood specimens were not collected, but placental transfer was estimated to have ranged from 29.0% to 46.0%. 36,38 The infants were born via cesarean section at 34 weeks' gestation, and received 2 days of enfuviritide, one week of nevirapine, and 2 weeks of didanosine. 38 At 4 months of age, neither infant was infected with HIV.…”

Section: Etravirine In Pregnancymentioning

confidence: 99%

“…36,38 The infants were born via cesarean section at 34 weeks' gestation, and received 2 days of enfuviritide, one week of nevirapine, and 2 weeks of didanosine. 38 At 4 months of age, neither infant was infected with HIV. The pharmacokinetics of etravirine were also retrospectively described in four pregnant women receiving the drug via a compassionate use exemption during the clinical development stage.…”

Section: Etravirine In Pregnancymentioning

confidence: 99%

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Profile of etravirine in the treatment of HIV in pediatrics

Dehority¹,

Viani

2013

PHMT

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Etravirine is a non-nucleoside reverse transcriptase inhibitor now licensed for treatment of human immunodeficiency virus (HIV)-1 infection in both children over 6 years of age and adults. Etravirine demonstrates a high genetic barrier to the development of resistance, as multiple mutations are typically required prior to the onset of reduced susceptibility to the drug. It retains in vitro and clinical activity against many HIV-1 isolates, demonstrating resistance to other non-nucleoside reverse transcriptase inhibitors, such as efavirenz and nevirapine. Given the ability of HIV to develop resistance rapidly across the non-nucleoside reverse transcriptase inhibitor class of antiretrovirals, etravirine has a welcome place in the management of HIVinfected patients, particularly treatment-experienced individuals harboring non-nucleoside reverse transcriptase inhibitor mutations. Etravirine has been shown to improve CD4 counts and viral load significantly in HIV-infected adults on combination antiretroviral therapy when compared with placebo in a large, randomized controlled trial. Data on the utility of etravirine in children are still somewhat limited, although a recent pediatric trial has demonstrated adequate pharmacokinetics, safety, and efficacy of etravirine in a small number of HIV-infected children and adolescents. In both children and adults, rash appears to be the most common adverse effect described. Despite its high genetic barrier to resistance, evidence of mutations conferring etravirine resistance has been documented in both adult and pediatric patients. Such mutations have been best described in treatment-experienced populations, including those who have never been exposed to the drug. This review describes the existing literature on the use of etravirine in the pediatric population, and highlights future and ongoing directions of investigation.

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Section: Etravirine In Pregnancymentioning

confidence: 95%

Section: Etravirine In Pregnancymentioning

confidence: 99%

Section: Etravirine In Pregnancymentioning

confidence: 99%

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Profile of etravirine in the treatment of HIV in pediatrics

Dehority¹,

Viani

2013

PHMT

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“…In resource-rich settings there are case reports of pregnant women with more extensive prior antiretroviral exposure who have evidence of high-level drug resistance and are failing a current regimen who are then treated with a variety of combination regimens, including enfuvirtide, which appears not to cross the placenta [20], and other investigational agents. Many providers in this setting have targeted newer drugs and combinations in patients with multidrug-resistant HIV along with focused adherence interventions with the goal of maximizing viral suppression at least through delivery despite limited data on teratogenicity.…”

Section: Antepartum Drug Resistancementioning

confidence: 98%

Complex Decisions in Managing HIV Infection During Pregnancy

2011

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Both the World Health Organization and the United States Department of Health and Human Services have recently substantially revised perinatal HIV treatment guidelines based on emerging data, much of it from the developing world. Management of HIV infection in pregnancy and delivery is complicated by concerns for maternal and fetal drug toxicity, acquisition of antiretroviral resistance, prior therapy, co-infections with other viruses, as well as incident opportunistic infections. Intrapartum and peripartum obstetric management, including the role of Caesarean section, continue to evolve in the setting of maternal HIV infection. Finally, new data have expanded the role of antiviral therapy in allowing safer infant feeding choices for HIV-infected mothers in resource-limited settings.

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“…Cord blood collected at delivery revealed detectable levels of etravirine. 61 The safety and pharmacokinetics of etravirine were examined in 5 women who received etravirine as part of compassionate use programs. Three women began etravirine with other antiretroviral therapy during the first trimester and the other 2 in the third trimester.…”

mentioning

confidence: 99%

The next generation: etravirine in the treatment of HIV-1 infection in adults refractory to other antiretrovirals

Rathbun¹,

Liedtke

2010

VAAT

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Etravirine is a second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) that is approved for the treatment of adult human immunodeficiency virus (HIV)-infected patients with documented or suspected resistance to first-generation NNRTIs. Etravirine has a flexible molecular structure that allows it to retain its activity against mutant HIV strains that exhibit resistance to first-generation agents. It is evident that 3 or more etravirine resistance-associated mutations are typically necessary before clinical resistance to etravirine. Safety and efficacy of etravirine are established in antiretroviral treatment-experienced patients in combination with antiretroviral regimens that contain darunavir/ritonavir. In phase III studies, cutaneous reactions occurred in 19% of treated patients and are the most commonly observed adverse event. The typical manifestation is the development of a maculopapular rash within the first few weeks of etravirine therapy. Resolution commonly occurs within 1-2 weeks on continued therapy. Rare cases of severe skin reactions (,0.1%) have been reported. Etravirine is hepatically metabolized by cytochrome P450 (CYP) 3A4, CYP2C9, and CYP2C19. Drug interactions with some antiretrovirals (eg, unboosted protease inhibitors and fosamprenavir/ ritonavir) and medications for other comorbidities (eg, atorvastatin and clarithromycin) have been reported and may require dosage adjustment for the coadministered drug or selection of alternative therapy in some instances. Administration of etravirine with potent inducers of CYP450 is not recommended due to the potential for subtherapeutic etravirine concentrations. In this article, the pharmacology, efficacy, safety, and tolerability of etravirine in adult treatmentexperienced patients with HIV-1 infection are reviewed. Medical literature was identified by MEDLINE and EMBASE searches (1966 to February 2010) using the search terms "etravirine", "TMC125", and "NNRTI".

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Successful use of darunavir, etravirine, enfuvirtide and tenofovir/emtricitabine in pregnant woman with multiclass HIV resistance

Cited by 37 publications

References 10 publications

Profile of etravirine in the treatment of HIV in pediatrics

Profile of etravirine in the treatment of HIV in pediatrics

Complex Decisions in Managing HIV Infection During Pregnancy

The next generation: etravirine in the treatment of HIV-1 infection in adults refractory to other antiretrovirals

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