HIV in Children

ANTIRETROVIRAL DRUGS

Dr. Ira Shah
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Last Updated : 1st September 2012

New Classes of Antiretroviral drugs


Entry Inhibitors

These agents inhibit viral binding or fusion to host target cells. T-20 (Enfurvirtide) is the drug currently used and has to be given subcutaneously twice daily and is to be used only in children > 6 years of age. It is a 36 amino acid peptide that binds to a region of the gp41 glycoprotein on the HIV cell surface and prevents virus-cell fusion. It is used as part of salvage regime in patients who have multi-antiretroviral therapy regime failures.

CCR5 co-receptor antagonist
Maraviroc blocks the chemokine CCR5 coreceptor on the CD4 cell surface thereby preventing HIVfrom entering the cell. This was the first antiretroviral drug to be developed that does not actually target the virus itself. Maraviroc is effective as part of Combination therapy in patients with multi-drug-resistant HIV-1. Before starting treatment with this drug, however, it is necessary to check for CCR5 or CXCR4 virus tropism. CCR5 antagonists will be inactive against CXCR4-tropic virus. Maraviroc is not yet routinely used in young children, but may be used in adolescents. There are considerable interactions with both PI and NNRTI classes, requiring alteration in maraviroc dosing depending on other drugs in the regimen.

Integrase Inhibitors
They block the integrase enzyme (See Chapter on Transmission and Pathogenesis) thereby preventing incorporation of viral DNA into human genome. Raltegravir and elvitegravir are integrase strand-transfer inhibitors (INSTIs). These drugs have been found to be useful in the treatment of patients with multi-drug-resistant HIV-1. Raltegravir is being evaluated in treatment-experienced children, but pharmacokinetic, safety, and efficacy data are not yet available and no pediatric formulation is commercially available.

Dosage recommendations of various ARVs


Dosing of various ARVs are based as per weight or surface area in children. The doses are depicted in Table 3.

NRTI NNRTI PI
  Recommendation   Recommendation   Recommendation
ZDV 360 mg/m2 to max 600 mg NVP 300-400 mg/m2 to max 400 mg NFV 110-150 mg/kg to max 2500 mg
3TC 8 mg/kg to max 300 mg EFV 15 mg/kg to max 600 mg LPVr 460/115 mg/m2 to max 800/200 mg
ABC 16 mg/kg to max 600 mg     RTV 700 mg/m2 to max 1200 mg
ddI 180 mg/m2 to max 400 mg        
d4T 2 mg/kg to max 80 mg        



ANTIRETROVIRAL DRUGS
Dr. Ira Shah
Incharge Pediatric HIV and TB Clinic, B.J.Wadia Hospital for Children, Mumbai, India Consultant in Pediatric Infectious Diseases, Nanavati Hospital, Mumbai, India.
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