Darunavir/ritonavir, etravirine and raltegravir combination has 'remarkable' success in children with resistant virus

A combination of darunavir/ritonavir, etravirine, and raltegravir is “remarkably” effective in HIV-positive adolescents with extensive prior experience of antiretroviral therapy, French investigators report in the November 13^th edition of AIDS. The study involved twelve adolescents, and all but one had a viral load below 400 copies/ml after a year of treatment with this combination. Impressive improvements in CD4 cell counts were observed and there were no serious side-effects.

“This [study] demonstrates that, as in adults, the majority of extensively treated adolescents can be virologically controlled with by a salvage regimen consisting of a combination of new drugs, despite a long record of suboptimal treatment and viral multiresistance,” write the investigators.

There is an urgent need for new antiretroviral drugs for HIV-positive children and adolescents who have a long history of HIV treatment and have extensive resistance to anti-HIV drugs.

Darunavir (Prezista)/ritonavir, etravirine (Intelence) and raltegravir (Isentress) are three new anti-HIV drugs that have been shown to be very effective in pre-treated adults with resistance to antiretrovirals.

Only darunavir is licensed for use in children aged 13 years and under, but a scheme in France allows 'off-label' use of medicines on compassionate grounds.

Paediatricians therefore treated twelve children and adolescents with extensive resistance to antiretroviral drugs with combinations that included darunavir/ritonavir, etravirine and raltegravir.

These patients had a median age of 15 years, and the median duration of antiretroviral therapy was also 15 years. All the individuals had HIV that was resistance to the main three classes of anti-HIV drugs.

On entry to the study, median viral load was approximately 100,000 copies/ml and median CD4 cell count was 124 cells/mm³.

Raltegravir was provided at a dose of 400 mg twice-daily, and nine of the patients were treated with adult doses of darunavir/ritonavir and etravirine.

Follow-up was at regular intervals over a twelve-month period. Final study analysis was conducted in October 2008.

None of the individuals developed a new AIDS-defining illness and there were no deaths. Only one patient discontinued treatment with a study drug because of side-effects (darunavir/ritonavir because of gasto-intestinal problems).

A month of treatment reduced median viral load to 200 copies/ml. After twelve months of therapy, median viral load was 50 copies/ml.

At the end of follow-up, all but one child had a viral load below 400 copies/ml.

CD4 cell count had increased to 500 cells/mm³ by the time of the twelve-month analysis.

There were no serious laboratory side-effects, nor were there any significant clinical side-effects, other than the already noted discontinuation of darunavir/ritonavir because of stomach problems.

“In this first pediatric observational analysis, the tolerability and efficacy of a combination of raltegravir, darunavir/ritonavir and etravirine appear remarkable”, comment the investigators.