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Five-Year Results From the Antiretroviral Research for Watoto (ARROW) Trial

March/April 2013

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Once- vs Twice-Daily Abacavir and 3TC Similar

The final presentation from ARROW was a poster showing findings from a further sub-study, a randomised comparison of once- vs twice-daily abacavir and 3TC in 669 children, authored by Victor Musiime and colleagues

The ARROW investigators previously demonstrated bioequivalence of plasma concentrations between abacavir and 3TC taken once- or twice-daily in 41 Ugandan children aged 3- 12 years.

In this comparison, children in ARROW receiving abacavir and 3TC-containing regimens twice-daily for at least 36 weeks, were randomised to remain on twice-daily or change to once-daily dosing (open-label). The children received single or co-formulated (Kivexa) antiretrovirals.


Primary outcomes were viral load at 48 weeks -- measured retrospectively with a 12% non-inferiority margin for suppression -- and study drug related grade 3/4 adverse events.

This study was conducted in a subgroup of 669 children who were a median age of 5.5 years (range 1.8-16.9), had a median CD4 percent of 33% and about half were girls. They were randomised to twice- daily (n = 333) vs once-daily (n=336) strategies after a median 1.8 years (range 0.9-3.0) on twice-daily abacavir and 3TC-containing first-line ART.

At the time of the twice-/once-daily randomisation, 51% vs 44%, 15% vs 22% and 34% vs 34% of children were receiving nevirapine, efavirenz and AZT respectively as their third drug. The majority (approximately 80%) took tablet formulations and the remainder syrups.

Over median 2.2 years follow-up, 98% vs 97% child-time was spent on twice- vs once-daily abacavir and 3TC in the two groups respectively. Self reported adherence was similar in the two groups.

There was no difference between groups in grade 3/4 or serious adverse events, WHO 3/4 events or weight- or height-for-age.

Proportions with viral load <80 copies/mL were similar in the twice- vs once-daily groups: at 48-weeks (n=661) there was a difference of -1.6% (95% CI, -8.4% to +5.2%), p = 0.65; at 96 weeks (n=539, assays ongoing) this was +0.7% (95%CI +6.9% to +8.3%), p=0.86.

Increases in CD4 percent in twice- vs once-daily were respectively +1.3% vs +0.8% at 48 weeks, p=0.25, and +2.5% vs +1.5% at 96 weeks, p = 0.06.

The investigators concluded that once daily dosing of abacavir and 3TC can be used to simplify treatment in children. Using efavirenz, this has the potential for a once-daily regimen.


ARROW gives us a very rich data set to further inform children's treatment, particularly in resource-limited settings.

The most recent U.S. guidelines include discussion on switching from twice-daily to once-daily dosing of 3TC at 8 to 10 mg/kg, based on review of data from the ARROW and PENTA 13 and 15 trials.7,8

Triple NRTIs are expected to be the preferred regimen for children receiving ART and TB treatment in the next WHO guidelines, according to the discussion at the WHO hosted satellite just before the opening of CROI 2013. These revised guidelines will be released at the International AIDS Society conference in Malaysia -- June 30 to July 3 2013.


Unless stated otherwise, all references are from the 20th Conference on Retroviruses and Opportunistic Infections (CROI), 3-6 March 2013, Atlanta.
Webcasts of the oral abstracts are fifth and sixth presentations at

  1. Kekitiinwa A et al. Impact of routine laboratory monitoring after ART initiation in 1206 HIV+ African children: the 5-year AntiRetroviral Research for Watoto trial. Oral abstract 85.
  2. Bwakura-Dangarembizi M et al. Randomised comparison of stopping vs continuing cotrimoxazole prophylaxis among 758 HIV+ children on long-term ART: the Anti-Retroviral Research for Watoto trial. Oral abstract 86.
  3. Nahirya-Ntege P et al. Short-term benefits of 4-drug 1st-Line ART do not persist with 3-drug maintenance in 1206 HIV+ African Children: The 5-Year ARROW Trial. Poster abstract 184LB.
  4. Musiime V et al. Randomised comparison of once- vs twice-daily abacavir and lamivudine among 669 HIV+ children in the Anti-Retroviral Research for Watoto Trial. Poster abstract 977.
  5. ARROW Trial Team. Routine versus clinically driven laboratory monitoring and first-line antiretroviral therapy strategies in African children with HIV (ARROW): a 5-year open-label randomised factorial trial. The Lancet, Early Online Publication, 7 March 2013. doi:10.1016/S0140-6736(12)62198-9
  6. Revill P et al. Within-trial cost-effectiveness analysis of clinically-driven vs laboratory and clinical monitoring for 1206 African children on ART: The AntiRetroviral Research for Watoto Trial. Poster abstract 949.
  7. U.S. paediatric guidelines updated. HTB. 1 February 2013.
  8. Panel on antiretroviral therapy and medical management of HIV-infected children. Guidelines for the use of antiretroviral agents in pediatric HIV infection.

Links to other websites are current at date of posting but not maintained.

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This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.

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