Effect of Lopinavir and Nevirapine Concentrations on Viral Outcomes in Protease Inhibitor-experienced HIV-infected Children

Abstract

Background Adequate exposure to antiretroviral drugs is necessary to achieve and sustain viral suppression. However, the target antiretroviral concentrations associated with long term viral suppression have not been adequately defined in children. Aim We assessed the relationship between plasma lopinavir or nevirapine concentrations and the risk of subsequent viremia in children initially suppressed on antiretroviral therapy. Methods After an induction phase of antiretroviral treatment, 195 children with viral suppression (viral load ≤400 copies/mL) were randomized to remain on a lopinavir/ritonavir-based regimen or to switch to a nevirapine-based regimen (together with lamivudine and stavudine). Viral load and lopinavir or nevirapine concentrations were measured at clinic visits 4, 8, 12, 16, 20, 24, 36, 52, 64 and 76 weeks post-randomization. Cox multiple failure event models were used to estimate the effects of drug concentrations on the hazard of viremia (viral load >50 copies/mL) Results At randomization, the median (IQR) age, CD4+ T-Lymphocyte percentage, weight-for-age and weight-for-height z-scores were 19 (16–24) months, 29 (23–37) %, −0.6(−1.3 to 0.2) and −3.2 (−4.1 to −2.1) respectively. The proportion of children with viral load 51–400 copies/mL at randomization was 43%. The hazard of subsequent viremia during follow-up was increased for lopinavir concentrations <1mg/L vs ≥1mg/L (adjusted hazard ratio 0.62 [95% CI, 0.40–0.94]) and for children with viral loads 51–400 copies/mL at randomization. Nevirapine concentrations were not significantly associated with subsequent viremia. Conclusion Plasma lopinavir concentrations predicted viral outcomes in children receiving lopinavir-based antiretroviral therapy. Our findings support a minimum target concentration of ≥1mg/L of lopinavir to ensure sustained viral suppression.

Tenofovir diphosphate levels in dried blood spots are associated with virologic failure and resistance to first‐line therapy in South Africa: a case–control cohort study

“…Despite its importance, accurately quantifying adherence has remained a challenge given the limitations of self-report and other subjective measures [9]. Pharmacologic measures of short-term adherence, such as antiretroviral concentrations in plasma, have been used to predict VF and drug resistance [10][11][12][13]. However, they are limited by their qualitative nature in relation to dosing [14].…”

Bioadhesive Food Protein Nanoparticles as Pediatric Oral Drug Delivery System

“…Nevertheless, C max was above the minimum therapeutic concentration (1 μg/mL) of LPV. 58 On the other hand, the ZWP nanoparticles increased the half-life of LPV by two-fold compared to the LPV/RTV formulation (Table 2). The ZWP nanoparticles increased the gastrointestinal residence time as reflected by the mean residence time (MRT).…”

“…This can be attributed to the sustained release of LPV from the ZWP nanoparticles, which is also supported by the lower absorption rate constant ( K a ) and higher T max . Nevertheless, C max was above the minimum therapeutic concentration (1 μg/mL) of LPV . On the other hand, the ZWP nanoparticles increased the half-life of LPV by two-fold compared to the LPV/RTV formulation (Table ).…”