Pharmacology and immuno-virologic efficacy of once-a-day HAART in African HIV-infected children: ANRS 12103 phase II trial

objective: to assess 12-month survival, pharmacokinetics, immunologic and virologic efficacy, tolerance, compliance and drug resistance in hiv-infected children in bobo-dioulasso, burkina faso, receiving once-daily highly-active antiretroviral therapy as a combination of didanosine (ddi), lamivudine (3tc) and efavirenz (efv). methods: in the anrs 12103 open phase ii trial, hiv-infected children were examined at inclusion and monthly thereafter. cd4+ t-lymphocyte (cd4) count, plasma concentration of ribonucleic acid (rna) of human immunodeficiency virus type 1 (hiv-1) and haematologic and biochemical parameters were measured at baseline and every trimester. hiv-1 resistance testing was performed in case of viral escape. drug plasma concentrations were determined with high-performance liquid chromatography. findings: from february 2006 to november 2007, 51 children (39% girls) with a mean age of 6.8 years were enrolled and treated for 12 months. at baseline, z scores for mean weight-for-age and mean height-for-age were -2.01 and -2.12, respectively. mean cd4% was 9.0. median plasma hiv-1 rna viral load was 5.51 log10 copies per millilitre (cp/ml). two children (3.9%) died and another 11 (22%) suffered 13 severe clinical events. at month 12, mean waz had improved by 0.63 (p < 0.001) and mean haz by 0.57 (p < 0.001). mean cd4% had risen to 24 (p < 0.001). viral load was below 300 rna cp/ml in 81% of the children; hiv resistance mutations were detected in 11 (21.6%). conclusion: the once-a-day combination of ddi + 3tc + efv is an alternative first-line treatment for hiv-1-infected children. dose adjustment should further improve efficacy.