Browsing by Author "Abrams, Elaine"

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    Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation
    (2015) Abrams, Elaine
    BackgroundEfavirenz, widely used as part of antiretroviral drug regimens in the treatment of paediatric human immunodeficiency virus infection, has central nervous system side effects. We describe four children presenting with serious, persistent central nervous system adverse events who were found to have elevated plasma efavirenz concentrations as a result of carrying CYP2B6 single nucleotide polymorphisms, known to play a role in the metabolism of EFV. None of the children had a CYP2B6 wildtype haplotype. We believe this is the first case of cerebellar dysfunction associated with efavirenz use to be described in children.Case presentationFour black African children, between the ages of 4 and 8years presenting between 1 and 20months post-efavirenz initiation, are described. Cerebellar dysfunction, generalised seizures and absence seizures were the range of presenting abnormalities. Plasma efavirenz levels ranged from 20-60mg/L, 5–15 times the upper limit of the suggested reference range. All abnormal central nervous system manifestations abated after efavirenz discontinuation.ConclusionEfavirenz toxicity should always be considered in human immunodeficiency virus-infected children with unexplained central nervous system abnormalities. Our findings further our understanding of the impact of genetic variants on antiretroviral pharmacokinetics in children across various ethnic groups. Screening for potential EFV-toxicity based on the CYP2B6 c.516 SNP alone, may not be adequate.
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    Systemic delays in the initiation of antiretroviral therapy during pregnancy do not improve outcomes of HIV-positive mothers: a cohort study
    (BioMed Central Ltd, 2012) Myer, Landon; Zulliger, Rose; Bekker, Linda-Gail; Abrams, Elaine
    BACKGROUND: Antiretroviral therapy (ART) initiation in eligible HIV-infected pregnant women is an important intervention to promote maternal and child health. Increasing the duration of ART received before delivery plays a major role in preventing vertical HIV transmission, but pregnant women across Africa experience significant delays in starting ART, partly due the perceived need to deliver ART counseling and patient education before ART initiation. We examined whether delaying ART to provide pre-ART counseling was associated with improved outcomes among HIV-infected women in Cape Town, South Africa. METHODS: We undertook a retrospective cohort study of 490 HIV-infected pregnant women referred to initiate treatment at an urban ART clinic. At this clinic all patients including pregnant women are screened by a clinician and then undergo three sessions of counseling and patient education prior to starting treatment, commonly introducing delays of 2-4weeks before ART initiation. Data on viral suppression and retention in care after ART initiation were taken from routine clinic records. RESULTS: A total of 382 women initiated ART before delivery (78%); ART initiation before delivery was associated with earlier gestational age at presentation to the ART service (p<0.001). The median delay between screening and ART initiation was 21days (IQR, 14-29days). Overall, 84.7%, 79.6% and 75.0% of women who were pregnant at the time of ART initiation were retained in care at 4, 8 and 12months after ART initiation, respectively. Among those retained, 91% were virally suppressed at each follow-up visit. However the delay from screening to ART initiation was not associated with retention in care and/or viral suppression throughout the first year on ART in unadjusted or adjusted analyses. CONCLUSIONS: A substantial proportion of eligible pregnant women referred for ART do not begin treatment before delivery in this setting. Among women who do initiate ART, delaying initiation for patient preparation is not associated with improved maternal outcomes. Given the need to maximize the duration of ART before delivery for prevention of mother-to-child HIV transmission, there is an urgent need for new strategies to help expedite ART initiation in eligible pregnant women.