Abstract
BackgroundThe World Health Organization recommends non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral therapy (ART) for children three years and older. In younger children, starting ART with lopinavir boosted with ritonavir (LPVr) results in lower risk of virological failure, but data in children three years and older are scarce, and long-term ART with LPVr is problematic in resource-poor settings.MethodologyRetrospective cohort of children three years and older who started triple ART including LPVr or a NNRTI between 2007 and 2013 in a rural setting in India. Children who started LPVr were switched to nevirapine-based ART after virological suppression. We analysed two outcomes, virological suppression (HIV-RNA <400 copies/ml) within one year of ART using logistic regression, and time to virological failure (HIV-RNA >1000 copies/ml) after virological suppression using Cox proportional hazard regression. A sensitivity analysis was performed using inverse probability of treatment weighting (IPTW) based of propensity score methods.FindingsOf 325 children having a viral load during the first year of ART, 74/83 (89.2%) in the LPVr group achieved virological suppression versus 185/242 (76.5%) in the NNRTI group. In a multivariable analysis, the use of LPVr-based ART was associated with higher probability of virological suppression (adjusted odds ratio 3.19, 95% confidence interval [CI] 1.11–9.13). After IPTW, the estimated risk difference was 12.2% (95% CI, 2.9–21.5). In a multivariable analysis including 292 children who had virological suppression and available viral loads after one year of ART, children switched from LPVr to nevirapine did not have significant higher risk of virological failure (adjusted hazard ratio 1.18, 95% CI 0.36–3.81).ConclusionsIn a cohort of HIV infected children three years and older in a resource-limited setting, an LPVr induction- nevirapine maintenance strategy resulted in more initial virological suppression and similar incidence of virological failure after initial virological suppression than NNRTI-based regimens.
Highlights
Due to higher viral loads, pharmacokinetic variability and suboptimal adherence because of complex regimens and frequent dosing adjustments, suppression of viral replication after initiation of antiretroviral therapy (ART) is more difficult to achieve in children than in adults [1]
In a cohort of HIV infected children three years and older in a resource-limited setting, an lopinavir boosted with ritonavir (LPVr) inductionnevirapine maintenance strategy resulted in more initial virological suppression and similar incidence of virological failure after initial virological suppression than nucleoside reverse transcriptase inhibitors (NNRTIs)-based regimens
In children,3 years, randomized control trials have demonstrated that the use of lopinavir boosted with ritonavir (LPVr) based regimens has lower risk of virological failure than ART containing nevirapine (NVP) [5,6]
Summary
Due to higher viral loads, pharmacokinetic variability and suboptimal adherence because of complex regimens and frequent dosing adjustments, suppression of viral replication after initiation of antiretroviral therapy (ART) is more difficult to achieve in children than in adults [1]. In children ,3 years, randomized control trials have demonstrated that the use of lopinavir boosted with ritonavir (LPVr) based regimens has lower risk of virological failure than ART containing nevirapine (NVP) [5,6]. In children .3 years, observational studies in resource-limited setting suggest that the use of PI-based ART is associated with lower risk of virological failure, but data are scarce [7,8]. The World Health Organization recommends non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral therapy (ART) for children three years and older. In younger children, starting ART with lopinavir boosted with ritonavir (LPVr) results in lower risk of virological failure, but data in children three years and older are scarce, and long-term ART with LPVr is problematic in resource-poor settings
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