Resistance patterns in asymptomatic HIV-infected children with moderate viral load treated with stavudine and didanosine.
Int Conf AIDS 2000 Jul 9-14; 13:40 (abstract no.. LbPeA7031)
De Mendoza C, Zamora L, Ciria L, Fortuny C, Gonzalez-Hinjos M, Garcia F, De Jose MI, Ramos JT, Asensil F, Soriano V Hospital Carlos III, Madrid, Spain. Fax: +34 91 733 66 14, E-mail: CMENDOZA@teleline.es.
A prospective, multicenter, open trial of d4T plus ddl in children with asymptomatic HIV infection, naive for anti-retroviral therapy or without treatment for the last 3 months, and with plasma viral load < 50,000 cop/ml was conducted in Spain. Sixteen children (M: 8; F: 8) were recruited from February 1998 to March 1999. Mean age was 6.75 years, mean CD4: 1,121 cell/ml (range: 368-2,736), and mean viral load (VL): 13,969 c/ml (1,152-48,000). CD4 and plasma VL were measured every 3 months. Plasma viremia was measured using Amplicor Monitor 1.5. Genotypic resistance to NRT1 was assessed by LiPA and an in-house point mutation assay for the codon 15 1 No drop-outs occurred during the 12 months study period. Undetectable VL (< 400 copies/ml) was reached in 9/16 (56.3%) subjects at nadir. At 12 months, 7/16 (43.7%) children still remained with undetectable viremia (< 400 copies/ml). Overall, mean VL reduction at 12 months from baseline was 1.27 logs. In those with virological failure, drug resistance testing did not show multi-nucleoside resistance genotypes (QI 5 1 M, T69SSS). Mutations linked to ddl (L74V or M I 84V) or to d4T (V75T) were neither recognized. However, other mutations were recognized in 4 (25%) patients. Two harbored T215Y, and two 41+215 mutants. One of the subjects carrying T215Y had been exposed previously to AZT, although he had stopped the drug two years before being included in the trial. This patient as well as the remaining subjects did not show nucleoside mutations at baseline for NRTIs.
CONCLUSIONS: The combination of d4T+ddI provides a satisfactory virological outcome at 1 year in children with moderate viral load at baseline, despite adherence issues often limit the benefit of treatment in this population. Resistance to d4T and ddI was not recognized. The low rate of drug resistance in the face of ongoing virus replication (even at low levels in most children) using d4T+ddI is in agreement with the high genetic barrier of these drugs.
Keywords: AEGIS, Stavudine, Didanosine, Viral Load, HIV, HIV Infections, Zidovudine, Anti-HIV Agents, HIV-1 Reverse Transcriptase, HIV Seropositivity, Viremia, Virus Replication, Genotype, Mutation, Spain, Child, Human, virology, genetics, AIDS 000709
LbPeA7031
