Salvage therapy with raltegravir in a 3-month-old infant

Background

The integrase inhibitor raltegravir (RAL) is widely used in adults. Only limited data are available for children and no data for infants. We describe the case of a three-month-old infant treated with RAL in combination with lopinavir/r (LPV/r) and lamivudine (3TC).

Methods

The mother emigrated from Ghana several years before and was insufficiently treated in a local hospital with AZT, 3TC and nevirapine (NVP) with constantly high plasma viral load (VL). At admission to the external birth clinic her VL was 160,000 copies/ml, the CD4 count 146/ml. The infant had a gestational age of 35 weeks with a birth weight of 1940g. A high-risk chemoprophylaxis with AZT, 3CT and NVP was given until the confirmation of a HIV1 infection three weeks later. The infant was then referred to our university hospital in an underweight state. His VL was 2.5Mio copies/ml, the CD4 count was 37% (2110c/ml). The genotypic resistance profile showed full resistance for all NRTIs and NNRTIs. We started an off-label therapy including RAL at 6mg/kg BID. The dosage was extrapolated from smaller trials in children ≥6 years of age. RAL is only available in 400mg tablets, so we pestled the tablet, attenuated the powder and distributed the required amount of mixture into a capsule. The content was then solved in water and administered by the mother. We combined RAL with LPV/r and 3CT BID which were dosed according to paediatric recommendations and adjusted monthly due to weight gain in closed cooperation with the pharmacologist.

Results

The therapy was well tolerated, no clinical or laboratory adverse events have occurred yet. The boy showed a catch-up growth and weight gain from <3rd percentile to >25th percentile at week 16 of therapy. In the same period his VL decreased from 1.8Mio copies/ml to 164 copies/ml and his CD4 count increased to 39% (3357c/ml). We performed a PK-profile and measured sufficient drug levels of RAL and LPV/r, comparable to the limited data of PK-studies conducted in older children. RAL Cmin: 146ng/ml, Cmax: 1960ng/ml, Tmax: 2h.

Conclusions

Due to the widely use of NNRTIs in developing countries an increasing number of mother-to-child transmissions of HIV with multi resistances can be expected in the near future. We describe a successful salvage therapy including RAL in a three-month-old infant. Further studies and investigation into the paediatric pharmacokinetics and application forms are warranted to confirm our results.