Technical Update On Treatment Optimization PDF Download

"The aim of this update is to provide information and guidance to countries on how best to use tenofovir (TDF) for the treatment of children with HIV. It is intended to complement the World Health Organization (WHO) normative guidelines on antiretroviral therapy (ART) and also support the goal of increasing access to simpler paediatric antiretroviral (ARV) formulations, in line with Treatment 2.0. TDF is recommended by WHO for use in adults and adolescents as a preferred first-line drug for the treatment of HIV infection, in combination with other ARVs. TDF is well tolerated and is available as a co-formulation with other ARVs to make dual or triple once-daily fixed-dose combinations. In this technical update, WHO has reviewed the currently available published and unpublished data on the safety, efficacy and dosing of TDF in children and adolescents. The US Food and Drug Administration (FDA) has approved TDF for use in adolescents and children above the age of two years. The recommended dose is 8 mg/kg body weight (up to a maximum of 300 mg), administered once daily using either an oral powder formulation or low-strength tablets. There are many potential benefits to using TDF in children--especially the ability to harmonize TDF-containing paediatric regimens with adult treatment recommendations, and the possibility of developing a once-daily paediatric fixed-dose combination. However, TDF also has potential risks. TDF toxicities have been investigated better in adults but there are some recent data from studies in children and adolescents. The main toxicities are decreases in bone mineral density (BMD), and glomerular and renal tubular dysfunction resulting in phosphaturia, hypophosphataemia and increased levels of parathyroid hormone. The TDF product label calls for patients with a history of pathological fracture and those at risk for osteoporosis to undergo BMD testing. It also recommends assessment of creatinine clearance before treatment initiation with TDF. In resource-limited settings, routine monitoring of creatinine clearance is frequently not possible. However, long-term data suggest that routine biochemistry testing does not improve patient outcome compared with clinical monitoring alone. When compared with population norms, HIV-infected children have lower-than-expected bone mass for their age and gender. This may be due to delays in growth, sexual maturity, time with HIV infection and disease severity. Bone turnover is higher in young children than in adults and adolescents because of skeletal growth. TDF-associated decreases in BMD correlate with young age, but also with a decline in viral load, suggesting that young virological responders may be at greater risk for loss of BMD if taking TDF. In addition, use of other ARVs, such as stavudine and protease inhibitors, especially ritonavir, is also associated with lower bone mass measurements. It is important to note that the clinical consequences of low BMD --related to either HIV or ART--remain unclear. Although bone fracture has not been observed in children treated with TDF, the impact of lower BMD on the long-term risk of osteoporosis and fracture is unknown."--Page 1.