Abacavir/3TC backbone proves most durable for children over five years

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HIV-positive children who take the nucleoside reverse transcriptase (NRTI) backbone of abacavir (Ziagen) and 3TC (lamivudine, Epivir) as part of their potent anti-HIV treatment regimen have better virological suppression and growth than children who take backbones comprising either AZT (zidovudine Retrovir) and 3TC or AZT and abacavir, according to five year results from the European PENTA 5 study presented to the Sixteenth International AIDS Conference in Toronto on Wednesday August 16th. The European investigators also found that virtually none of the asymptomatic children in the PENTA 5 study who started therapy with just two NRTIs had sustained suppression of HIV.

The PENTA 5 study was a 48-week, randomised controlled trial, designed to compare the safety and efficacy of three NRTI backbones. Children who had symptoms of HIV infection took their allotted treatment with the protease inhibitor (Viracept), but the minority of children participating in the study who were asymptomatic were randomised to receive either nelfinavir or a placebo.

A total of 128 children were recruited to the study, with data available for 124 children at week 48. After five years of follow-up, 39% of children who initially took AZT and 3TC had changed therapy, compared to 46% of those who initiated treatment with AZT and abacavir and 31% of children who commenced treatment with abacavir and 3TC.

Glossary

asymptomatic

Having no symptoms.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

fixed-dose combination (FDC)

Two or more drugs contained in a single dosage form, such as a capsule or tablet. By reducing the number of pills a person must take each day, fixed-dose combination drugs may help improve adherence.

When the investigators looked at the reasons for switching treatment, they noted that patients taking abacavir/3TC were significantly less likely to change therapy with a undetectable viral load than patients in either of the other two treatment arms, indicating the tolerability of the abacavir/3TC regimen.

The investigators then looked at the viral loads for the 105 children for whom measurements were available at year five. Of the children who took the AZT/3TC backbone, 55% had a a viral load below 400 copies/ml and 32% had a viral load below 50 copies/ml. Only 50% of the children who took abacavir and AZT had a viral load below 400 copies/ml at year five, with 25% having a viral load below 50 copies/ml at this point. However, 79% of children who took abacavir/3TC had a viral load below 400 copies/ml at year five, and 63% of the abacavir/3TC-treated children had a viral load below 50 copies/ml at this time.

Furthermore, the investigators found that the log10 decreases in viral load from baseline were greatest for patients taking abacavir/3TC (3.4log10, versus 2.5 log10 for both of the other study combinations, p = 0.001). Increases in CD4 cell percentage were, however, comparable between the three arms of the study.

Both weight-for-age and height-for-age were significantly better for children taking abacavir/3TC than children taking either of the two other combinations (p = 0.02).

A small number of asymptomatic children were randomised to receive dual NRTI therapy only. These children had a significantly poorer virological outcome, with only a small minority of patients still taking two drugs five years later. Furthermore, none of seven children randomised to take only AZT/3TC had a viral load below 400 copies/ml; only one of the eleven children taking abacavir/AZT and three of the six children randomised to take abacavir/3TC had achieved this outcome.

Dr Diana Gibb of the UK's Medical Research Council said: "3TC/abacavir appears to be an excellent forst-line nucleoside analogue backbone for children. The combination is made up of similar small volumes of liquid, but we need a fixed dose combination 3TC/abacavir pill for children."

References

Gibb DM et al. 3TC+ABC maintains virological superiority over ZDV+3TC and ZDV+ABC over 5 years in children: the PENTA 5 trial. Sixteenth International AIDS Conference, Toronto, abstract WeAb0302, 2006.