Browsing by Subject "Human immunodeficiency virus 1"

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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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    Open Access
    Incidence of cytological abnormalities within 24 months of a normal cervical smear in Soweto, South Africa
    (2012) Adam, Yasmin; McIntyre, James Alasdair; de Bruyn, Guy
    BACKGROUND: A screening programme for cervical cancer has been implemented in South Africa (SA) with intervals of 10 years after a normal cytological result. There are no studies that evaluate repeat screening at a shorter interval in SA. OBJECTIVES: (i) To find the incidence of cytological abnormalities on a repeat test after a report of normal cytology or an inadequate Pap smear; and (ii) to explore the factors associated with an abnormal cytology on repeat testing. METHODS: This was a secondary data analysis of a randomised controlled trial of diaphragm, lubricant gel and condoms v. condoms in the prevention of HIV infection. HIV-negative women were recruited between November 2003 and December 2005, with a normal Pap smear at entry. Observation time was from the first Pap smear to the date of the repeat Pap smear. Explanatory variables used were baseline, excepting any new HIV infection. RESULTS: The incidence of cytological abnormalities was 6.48% yearly in women with a previously normal Pap smear and 11.71% yearly in women with an inadequate smear result (p=0.03). The incidence of high-grade squamous intra-epithelial lesions (HSILs) was <0.5%. Factors associated with abnormal cytology were a history of ectopic pregnancy (odds ratio (OR) 9.25; confidence interval (CI) 1.78 - 48.02; p=0.01), number of male partners (OR 1.12; CI 1.03 - 1.22; p=0.01), history of vaginal discharge (OR 13.95; CI 1.18 - 164.47; p=0.04), and incident HIV infection (OR 6.56; CI 1.14 - 38.16; p=0.04). CONCLUSION: The incidence of HSILs is low in the first 2 years after a normal or inadequate Pap smear, even in a setting with a high prevalence of cytological abnormalities.