Therapeutic Drug Monitoring of Lopinavir in HIV-Infected Children on Second-Line Antiretroviral Therapy in Asia

Abstract

Background Failure rates of second-line boosted protease inhibitor antiretroviral therapy regimens in children rise over time. Therapeutic drug monitoring (TDM) can contribute to assessments of adherence. The authors assessed the performance characteristics of the US DHHS-recommended lopinavir (LPV) concentration of 1.0 mg/L for predicting virologic failure (VF) and intermediate-to-high level LPV resistance in Asian children. Materials and Methods LPV concentration, HIV RNA level, and adherence data from study participants in Indonesia, Thailand, and Vietnam receiving second-line LPV-based ART and followed for ≥24 weeks were analyzed. Results A total of 223 children at a median age of 10.4 (interquartile range, IQR 7.9–13.4) years were enrolled, 61% were male. Their mean CD4 was 842±438 cells/mm3, and the median LPV duration was 2.5 (IQR 1.3–4.2) years. Five out of 84 (6%) and 18 out of 139 (13%) children had LPV trough and random concentrations <1.0 mg/L at study week 24. Using either of these trough or random LPV concentrations, a cutoff at 1.0 mg/L gave an area under the receiver operating characteristics (AROC) curve of 0.69 in predicting VF with sensitivity of 44% (95% CI 23–66) and specificity of 94% (95% CI 89–97). Seven of 21 with VF and resistance results available had ≥1 major protease inhibitor mutation. Multivariate logistic regression found LPV concentrations <1.0 mg/L (OR 6.47; 95% CI 2.15–19.50, P = 0.001) and CD4 ≤20% (OR 2.83; 95% CI 1.01–7.89, P = 0.05) were independently associated with HIV RNA >1000 copies/mL. No factors predicted major LPV resistance mutations. Conclusions The authors support that the DHHS target LPV concentration of <1.0 mg/L is predictive of virologic failure (VF), but not of the presence of major LPV mutations.

The relative contributions of HIV drug resistance, nonadherence and low-level viremia to viremic episodes on antiretroviral therapy in sub-Saharan Africa

“…Further studies are needed to provide insights on the etiology of VE with integrase 10 inhibitors, following the transition to dolutegravir-based ART. Second, our study relied on a selfreported adherence measure, which, although valid and widely used, has potential for underestimating the effect of non-adherence on VE [28][29][30]. Viral load and therapeutic drug monitoring tests are more objective and are thus preferred alternatives.…”

Virological failure of antiretroviral therapy and associated social and clinical factors in children and adolescents living with HIV

“…Воз можным объяснением является то, что в первой и во второй группе пациенты имеют плохую привер женность к терапии, поэтому у них наблюдается высокий процент пациентов с нулевыми концен трациями данных препаратов. Согласно опубли кованным данным, минимальные концентрации лопинавира в плазме крови связаны с ухудшением вирусологического ответа на АРТ [27].…”

Nevirapine plasma concentration is associated with virologic failure and the emergence of drug-resistant mutations among HIV patients in Kenya: A cross sectional study

“…[7,8] Although several reports have linked plasma NVP concentrations with varied treatment outcomes, [9] in many developing nations, Kenya, including therapeutic drug monitoring, has not yet been integrated into HIV management programs. [8,10]…”

“…[7,8] Although several reports have linked plasma NVP concentrations with varied treatment outcomes, [9] in many developing nations, Kenya, including therapeutic drug monitoring, has not yet been integrated into HIV management programs. [8,10] Multiple factors contribute to ART treatment outcomes, including high interpatient variability. [11] These factors are partly due to differences in host genetics and drug metabolism, thus supporting the need for therapeutic drug monitoring to boost the clinical management of HIV.…”