Browsing by Author "Cotton, Mark F."

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    Antiretroviral Drugs for Preventing Mother-to-Child Transmission of HIV: A Review of Potential Effects on HIV-Exposed but Uninfected Children
    (2011) Heidari, Shirin; Mofenson, Lynne; Cotton, Mark F.; Marlink, Richard; Cahn, Pedro; Katabira, Elly
    Objective Antiretroviral drugs (ARVs) can prevent HIV mother-to-child transmission (PMTCT), but in utero ARV exposure may be associated with neurologic symptoms due to mitochondrial toxicity (MT). We sought to identify the currently recommended PMTCT regimen that optimally balances risks of pediatric HIV infection and neurologic MT. Design Published MTCT and MT data were used in a decision analytic model of MTCT among women in sub-Saharan Africa. Methods We investigated the HIV and MT risks associated with no ARV prophylaxis and five recommended regimens ranging from single-dose nevirapine to 3-drug ART. Sensitivity analyses varied all parameters, including infant feeding strategy and the disability of MT relative to HIV. Results Provision of no ARVs is the least effective and least toxic strategy, with 18-month HIV risk of 30.4% and MT risk of 0.2% (breastfed infants). With increasing drug number and duration, HIV risk decreases markedly (to 4.9% with 3-drug ART), but MT risk also increases (to 2.2%, also with 3-drug ART). Despite increased toxicity, 3-drug ART minimizes total adverse pediatric outcomes (HIV plus MT), unless the highest published risks are true for both HIV and MT, or the disability from MT exceeds 6.4 times that of HIV infection. Conclusions The risk of pediatric MT from effective PMTCT regimens is at least an order of magnitude lower than the risk of HIV infection associated with less effective regimens. Concern regarding MT should not currently limit the use of 3-drug ART for PMTCT where it is available.