ObjectiveLimited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors.MethodsData from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis.ResultsThe study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033).ConclusionMajor protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed.

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Post-print version. Full reference: Feucht UD, Meyer A, Thomas WN, Forsyth BWC, Kruger M. Early diagnosis is critical to ensure good outcomes in HIV-infected children -Outlining barriers to care. Published: AIDS Care. 2015. doi: 10.1080/09540121.2015.1066748 Abstract HIV-infected children require early initiation of antiretroviral therapy (ART) to ensure good outcomes. The aim was to investigate missed opportunities in childhood HIV diagnosis leading to delayed ART initiation.Baseline data was reviewed of all children aged <15 years referred over a one-year period for ART initiation to the Kalafong Hospital HIV services in Gauteng, South Africa. Of the 250 children, one quarter (24.5%) were of school-going age, 34.5% in the preschool group, 18% between 6-12 months old and 23% below six months of age (median age=1.5 years [IQR 0.5-4.8]). Most children (82%) presented with advanced/severe HIV disease, particularly those aged 6-12 months (95%). Malnutrition was prominent and referrals were mostly from hospital inpatient services (61%).A structured caregiver interview was conducted in a subgroup, with detailed review of medical records and HIV results. The majority (≥89%) of the 65 interviewed caregivers reported good access to routine healthcare, except for postnatal care (26%). Maternal HIV-testing was mostly done during the 2 nd & 3 rd pregnancy trimesters (69%). Maternal non-disclosure of HIV status was common (63%) and 83% of mothers reported a lack of psychosocial support. Routine infant HIV-testing was not done in 66%, and inadequate reporting on patient-held records (Road-toHealth Cards/Booklets) occurred frequently (74%). Children with symptomatic HIV disease were not investigated at primary healthcare in 53%, and in 68% of families the siblings were not tested. One-third of children (35%) had a previous HIV diagnosis, with 77% of caregivers aware of these prior results, while 50% acknowledged failing to attend ART-services despite referral.In conclusion, a clear strategy on paediatric HIV case finding, especially at primary healthcare, is vital. Multiple barriers need to be overcome in the HIV care pathway to reach high uptake of services, of which especially maternal reasons for not attending paediatric ART services need further exploration.