3TC/abacavir maintains virological superiority over AZT/3TC and AZT/abacavir beyond 5 years in children

HIV Treat Bull - Vol. 7, No. 7/8, September 2006

There are have been few randomised trials in naïve children directly comparing ART combinations.Di Gibb presented findings from 5-year follow up of the PENTA 5 trial. This was a 48-week randomised controlled trial comparing three dual NRTI combinations with or without NFV as first line ART therapy.

128 children were randomised, one died and one was lost to follow up within two weeks of randomisation. Asymptomatic children (n=55) were also randomised to NFV or placebo; all other children received open-label NFV. 126 were followed after 48 weeks: AZT+3TC (n=36), AZT+ABC (n=44) or 3TC +ABC (n=46).

Median follow-up was 5.8 years (range: 3.1-7.8 years) and only 18 children (14%) had less than 5 years follow up. The authors reported 94% AIDS-free survival at 5 years in all arms.

The investigators found that, as expected, the proportion of child-time taking randomised antiretroviral drugs decreased over time. Between 2.5 to 5 years the proportion of children still taking their randomised NRTIs was lower in both AZT groups: AZT/3TC 61%, AZT/ABC 54% and 3TC/ABC, 69%.

By 5 years, 63/126 children (50%) were still taking randomised NRTIs; 19 (53%) AZT/3TC, 16 (36%) AZT/ABC and 28 (61%) 3TC/ABC. However, 18% (3/17) AZT/3TC, 50% (14/28) AZT/ABC and 50% (9/18) 3TC/ABC of the changes from randomised NRTIs were either early single drug substitutions for toxicity (<24 weeks after randomisation) or switches in children for viral suppression (HIV-1 RNA <400 copies/ml) for simplification, toxicity or carer/child request.

At year five viral load data were available for 105 children and 62% (65/105) of children were <400copies/mL. Of these 55%/32% AZT+3TC ; 50%/25% AZT+ABC; and 79%/63% 3TC/ABC had VL <400/<50 copies/ml respectively (p=0.03/p=0.003).

There were corresponding decreases in log₁₀ VL: 2.3, 2.5 and 3.4 respectively (p=0.001). The mean increase in CD4% was 12%, 9% and 12% (p=0.2); height-for-age 0.42, 0.68 and 1.05 (p=0.02); weight-for-age 0.03, 0.13 and 0.75 (p=0.02).

Reverse transcriptase resistance mutations were different between the arms:

AZT/3TC (n=4): 41, 67, 70, 184, 210 and 215; AZT/ABC (n=6): n=4 maintained wild-type virus, n=2 developed TAMs 41, 67, 70, 210, 215, 219; 3TC/ABC (n=6): 65, 74, 115, 184.

Of the 24 children randomised to dual NRTI only, 0/7 AZT/3TC, 3/11 AZT/ABC and 4/6 3TC/ABC were still taking only 2 drugs at year 5 (0, 1, and 3 with VL <400 copies/ml).

Dr Gibb concluded that 3TC/ABC sustained long term virological superiority; the short-term benefits in terms of growth persisted and lower rates of switching with detectable viral load were observed compared to the other two NRTI backbones.

She also noted that this backbone can be taken once daily in children >3years and once again made the case for a “combined scored baby pill.”

Ref: Gibb DM, Green H, Saidi Y et al. 3TC +ABC maintains virological superiority over ZDV+3TC and ZDV+ABC beyond 5 years in children. Oral abstract WEAB0302.

2006-09-10
IB060709-19

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