Review of Tenofovir Use in HIV-Infected Children
The World Health Organization guidelines recommend TDF instead of thymidine analoge NRTIs (stavudine and zidovudine) for first-line ART regimens in adults and children older than 10 years of age. Studies in adults demonstrated lower virologic failure rates for TDF/emtricitabine compared to abacavir/lamivudine when given as a once daily dose regimen with either efavirenz or atazanavir/r, and also when compared to regimens with a zidovudine/lamivudine backbone. The TDF/lamivudine/efavirenz regimen has comparable virologic efficacy to stavudine/lamivudine/efavirenz; however, it is associated with better lipid profiles and a lower rate of lipodystrophy in antiretroviral-naive adults. In 2014, the US Department of Health and Human Services guidelines recommended TDF as a preferred option for adolescents in Tanner stages 4–5 and as an alternative regimen for those in Tanner stage 1–3. The reluctance of experts to recommend TDF as a first-line in children of all ages is due to limited information about long-term safety and especially bone toxicity. Abacavir, a cytidine analoge, can be administered to young children once daily and, like TDF, does not induce multi-NRTI resistant mutation. The drawbacks of abacavir are its cost, lack of wide availability in resource-limited settings, and the need to screen for the human leukocyte antigen HLA-B*5701 allele to reduce the risk of drug hypersensitivity. However, screening for may be less of a concern for Southeast Asian or African population who have a low prevalence of HLA-B5701.
An in vitro study has shown that using TDF and zidovudine concomitantly modulates mutation selection; fewer resistance mutations to either drugs emerge because of a mutually antagonistic drug resistance interaction.Some experts choose a combination of TDF and zidovudine as NRTIs to construct a second-line or third-line ARV regimen for heavily pretreated patient.
Position of TDF in Antiretroviral Treatment
TDF as Part of First-line ARV Regimen
The World Health Organization guidelines recommend TDF instead of thymidine analoge NRTIs (stavudine and zidovudine) for first-line ART regimens in adults and children older than 10 years of age. Studies in adults demonstrated lower virologic failure rates for TDF/emtricitabine compared to abacavir/lamivudine when given as a once daily dose regimen with either efavirenz or atazanavir/r, and also when compared to regimens with a zidovudine/lamivudine backbone. The TDF/lamivudine/efavirenz regimen has comparable virologic efficacy to stavudine/lamivudine/efavirenz; however, it is associated with better lipid profiles and a lower rate of lipodystrophy in antiretroviral-naive adults. In 2014, the US Department of Health and Human Services guidelines recommended TDF as a preferred option for adolescents in Tanner stages 4–5 and as an alternative regimen for those in Tanner stage 1–3. The reluctance of experts to recommend TDF as a first-line in children of all ages is due to limited information about long-term safety and especially bone toxicity. Abacavir, a cytidine analoge, can be administered to young children once daily and, like TDF, does not induce multi-NRTI resistant mutation. The drawbacks of abacavir are its cost, lack of wide availability in resource-limited settings, and the need to screen for the human leukocyte antigen HLA-B*5701 allele to reduce the risk of drug hypersensitivity. However, screening for may be less of a concern for Southeast Asian or African population who have a low prevalence of HLA-B5701.
TDF as Part of Second-line or Third-line ARV Regimens
An in vitro study has shown that using TDF and zidovudine concomitantly modulates mutation selection; fewer resistance mutations to either drugs emerge because of a mutually antagonistic drug resistance interaction.Some experts choose a combination of TDF and zidovudine as NRTIs to construct a second-line or third-line ARV regimen for heavily pretreated patient.
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