Encouraging results with cut up generic fixed dose combination tablets in Uganda

Linda Barlow-Mosha from the Makerere University/John Hopkins University research collaboration (MU-JHU), Uganda reported detailed findings from a smaller Ugandan study, in which children also received cut up Triomune tablets.

HIV-infected children from the MU-JHU and the Paediatric Infectious Disease Clinic, Mulago were screened for antiretroviral therapy. One hundred and sixty four were screened and 90 were enrolled and 81 received quartered or halved Triomune according to the childs weight band. The investigators found quartered tablets problematic and flaking so very small children were changed to syrups.

The median age of the children was 5 years (range 1-14 years) and 48% were girls. 26% had a CD4% <5% and 67% between 5% and 15%.

The childrens median baseline CD4% was 9%, which rose to 17%, 23%, 27% and 32% at weeks 12, 24, 36 and 48 respectively (p<0.0001). At 48 weeks 96% (22/23) children had CD4% >15% and 83% (19/23) have viral load <400 copies/mL. 42% (8/19) of children with viral loads <400 copies/ml were exposed to single dose nevirapine in MTCT programmes.

Four children have died, 3/4 were at WHO stage III at initiation of therapy, 2/4 had CD4% baseline <1%.

72 children remain on Triomune. Fourteen children receive alternate regimens, 8 because they weighed <13kg, I child had a hepatoxicity reaction to nevirapine, 4 children had rash and one virological failure.

Four children failed to achieve viral load <400 copies/mL at 48 weeks. The investigators reported that treatment failure was associated with high baseline viral load >750,000 copies/mL, poor adherence to syrups, and exposure to single dose nevirapine.

Dr Barlow-Mosha reported good adherence to therapy (95% in 90% of children) and she noted that adherence to tablet formulations is better than to syrups. Her message to the pharmaceutical industry: Children need tablets.

The investigators are still monitoring the effect of response after single dose nevirapine exposure and plan a study to compare exposed with unexposed children.

Comment

One critical thing about the cut-up Triomune is the fragmentation of the tablets (quarters not feasible). Halving tablets would be helped by manufacturers taking the simple step of scoring tablets. This is something that Abbott could usefully do with Meltrex (it isn’t currently planned).

And although this strategy is important and is now in some national guidelines (Malawis for example), this is not a long term solution as cut up tablets for very young (<2 years) result in relative underdosing of the NVP component. For this reason, generic companies are looking at different dosed FDCs for babies. For example Ciplas Pedimune comes in junior or baby which has relatively more nevirapine (and the tablets are scored). If only all antiretroviral manufacturers would take more interest in medicines for children.

Barlow-Mosha L, Musoke P, Ajuna P et al. Early effectiveness of Triomune in HIV-infected Ugandan children. 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, 2005. Abstract WeOa0103.