Twice as many patients in the 400/100 mg group

(62%) had an increase in total bilirubin (>2.5 times the upper limit of normal) as in the 300/100 mg group (30%). Atazanavir (ATV) was well tolerated with no unanticipated adverse events. In this study, use of atazanavir/RTV 300/100 mg qd produced Cmin comparable to historical data in nonpregnant HIV-infected adults. When used in combination with zidovudine/lamivudine, it suppressed HIV RNA in all mothers and prevented mother-to-child transmission of HIV-1 infection. During pregnancy, the pharmacokinetics, safety and efficacy demonstrated that a dose adjustment is not required for ATV. Treatment guidelines for HIV-1 infection in pregnant women recommend highly active antiretroviral (ARV)

therapy (HAART) with two nucleoside Selleckchem GSK3235025 reverse transcriptase Trametinib molecular weight inhibitors (zidovudine and lamivudine) plus the nonnucleoside reverse transcriptase inhibitor nevirapine [1–3]. Some guidelines also recommend the ritonavir (RTV)-boosted protease inhibitor lopinavir as an optional third agent [1], although others recommend several boosted protease inhibitors as optional agents [2]. All other ARV drugs are alternative agents or for use in special circumstances [1,4]. However, there are questions and concerns regarding the two most frequently recommended third agents: treatment initiation with nevirapine is associated with an increased risk of symptomatic liver toxicity, often accompanied by a rash, which is potentially fatal [1,5]. Concerns with RTV-boosted lopinavir include uncertainty regarding whether an adjusted dose is necessary during pregnancy [6–8], and the common side effects of diarrhoea, nausea and vomiting and elevation of plasma lipids [9,10]. Therefore,

an unmet medical need exists for additional recommended third agents for use during pregnancy. Atazanavir (ATV) is a potent, well-tolerated, once-daily Cyclin-dependent kinase 3 (qd) HIV protease inhibitor, with established efficacy in both treatment-naïve and treatment-experienced adult, nonpregnant HIV-infected patients [11,12] and is included as a preferred treatment option for nonpregnant HIV-infected patients [2]. HIV protease inhibitor drug levels are generally reduced during pregnancy [13–16], especially during the third trimester, because of metabolic and physiological changes associated with pregnancy [17]. In one study of lopinavir/RTV, compensation for the lower exposures required a dose increase to 533/133 mg twice daily (bid) from 400/100 mg bid in the third trimester to produce exposures similar to those in nonpregnant historical controls [7]. Conversely, Ripamonti et al. [18] reported that the standard dose of ATV/r (300/100 mg) resulted in ATV exposures in women in the third trimester that were similar to their postpartum exposures.