Background In resource-limited settings, many patients, with no prior PI treatment on a second-line, high genetic barrier, ritonavir boosted protease inhibitor (PI) containing regimen have virologic failure. Methods We conducted a cross-sectional survey to investigate the aetiology of virologic failure in two public health antiretroviral clinics in South Africa documenting the prevalence of virologic failure (HIV RNA load > 500 copies/ml) and genotypic antiretroviral resistance; and lopinavir hair and plasma concentrations in a nested case-control study. Results Ninety three patients treated with a second-line regimen including lopinavir boosted with ritonavir were included, of whom 50 (25 cases, with virologic failure and 25 controls) were included in a nested case control study. Of 93 patients 37(40%) had virological failure, only 2 of which had had major protease inhibitor mutations. The negative predictive values: probability of failure with lopinavir plasma concentration > 1μg/mL or hair concentrations > 3.63ng/mg for virologic failure were 86% and 89%, and positive predictive values of low concentrations 73% and 79%, respectively, whereas all virologic failures with HIV RNA loads above 1000 copies/ml, of patients without protease inhibitor resistance, could be explained by either having a low lopinavir concentration in plasma or hair. Conclusions Most patients who fail a LPV/r regimen, in our setting, have poor lopinavir exposure. A threshold plasma lopinavir concentration (indicating recent LPV/r use) and/or hair concentration (indicating longer term lopinavir exposure) are valuable in determining the aetiology of virologic failure and identifying patients in need of adherence counselling or resistance testing.

Since the advent of highly active antiretroviral therapy (HAART), the treatment of human immunodeficiency virus (HIV) infection has become more potent and better tolerated. While the current treatment regimens still have limitations, they are more effective, more convenient, and less toxic than regimens used in the early HAART era, and new agents, formulations and strategies continue to be developed. Simplification of therapy is an option for many patients currently being treated with antiretroviral therapy (ART). The main goals are to reduce pill burden, improve quality of life and enhance medication adherence, while minimizing short- and long-term toxicities, reducing the risk of virologic failure and maximizing cost-effectiveness. ART simplification strategies that are currently used or are under study include the use of once-daily regimens, less toxic drugs, fixed-dose coformulations and induction-maintenance approaches. Improved adherence and persistence have been observed with the adoption of some of these strategies. The role of regimen simplification has implications not only for individual patients, but also for health care policy. With increased interest in ART regimen simplification, it is critical to study not only implications for individual tolerability, toxicity, adherence, persistence and virologic efficacy, but also cost, scalability, and potential for dissemination and implementation, such that limited human and financial resources are optimally allocated for maximal efficiency, coverage and sustainability of global HIV/AIDS treatment.

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A low WAZ is associated with poor survival in children. Nutritional status should receive more attention in HIV disease classification in children. Parent utilization of the clinic was inadequate. Even in the absence of HAART, extended survival in children is possible.

NCT01489527; Post-results.