The success of antiretroviral therapy (ART) has dramatically changed the prognosis and natural history of pediatric HIV infection. A significant decline in morbidity and mortality has led to an increasing number of children entering their adolescent years.^[1] Current treatment strategies aim at improving quality of life for HIV-infected children and adolescents so that they can enter adult life as healthy as possible. Ongoing efforts have been made to develop novel antiretroviral agents with greater potency, higher tolerability and better safety profiles for the young population who need life-long therapy.

Tenofovir disoproxil fumarate (TDF) is an orally bioavailable ester prodrug of tenofovir (TFV). It is a nucleotide reverse-transcriptase inhibitor which has demonstrated inhibitory activity against HIV and also hepatitis B virus (HBV). Its active metabolite, intracellular TFV diphosphate (TFV-DP), is a competitive inhibitor of HIV-1 reverse-transcriptase enzyme and terminates the growing DNA chain. TDF has a long serum half-life of 17 hours which allows for convenient once-daily dosing. The intracellular half-life of TFV-DP ranges from 70 to 150 hours regardless of concomitant ART used.^[2–5] In the fasting state, 25% of the drug is absorbed, with bioavailability increasing to 40% when administered with a high-fat-meal.^[6] TFV is mainly eliminated unchanged by the kidneys; thus, dose adjustment is required in patients with significant renal impairment. TFV is not a substrate, inducer or inhibitor of the cytochrome p450 enzyme system. It appears less likely to cause mitochondrial toxicity when compared to nucleoside reverse-transcriptase inhibitors (NRTIs).^[7] This property may explain why TDF has less of an effect on lipid profiles and lower risk of lipodystrophy compared to many NRTIs.

In HIV-infected adults, TDF is a recommended first-line drug, replacing the thymidine analoge NRTIs stavudine and zidovudine. There are several fixed-dose combinations (FDC) that contain TDF: TDF/emtricitabine/efavirenz (Atripla),^[8] TDF/emtricitabine/rilpivirine (Complera)^[9] and TDF/emtricitabine/elvitegravir/cobicistat (Stribild).^[10] Other TDF-containing FDC's are still in clinical trials including TDF/lamivudine/efavirenz (Matrix Laboratories Ltd, Hyderabad, India; www.clinicaltrials.govidentifier: NCT01160120). The once-daily co-formulated agents with simple dosing requirements can help improve adherence.^[11] This could make the difference between success and failure of ART, especially for adolescents.^[12] However, currently, there is no TDF-containing FDC available for preadolescent children.