Background:  From December 2006 to December 2007, 23 consecutive adolescents with multidrug- resistant HIV1 were treated in France with raltegravir (RAL) on compassionate grounds in line with regulatory statement granted by the French health authority before market commercialization of a drug. RAL was used in combination with other antiretroviral drugs including for 13 patients both etravirine (ETV) and darunavir (DRV), these 2 drugs also being delivered via a similar expanded access.

Methods:  The 23 patients had a median age of 15.5 years (range 12 to 17) and have been HIV-infected since birth. They had previously received a median of 6 NRTI (range 5 to 7) and 4 PI (2 to 7), all except 1 patient had been treated with 1 or 2 NNRTI, and 13 have received enfuvirtide. A history of AIDS was recorded for 17 patients; 21 of the patients were treated because of active replication of multidrug-resistant virus (median HIV-1 RNA level of 5 log₁₀ copies/mL). The number of antiretroviral drugs prescribed in combination with RAL was 2 to 5. ETV was used in 16 patients, DRV in 17 and both drugs in 13.

Results:  The median follow-up of treatment including RAL was 9 months (6 to 18) for 22 patients. Treatment of 1 patient was interrupted after 3 weeks because of headache. No additional moderate-to-severe clinical side effect and no grade 3 or 4 laboratory abnormalities occurred. At the last follow-up, HIV-1 RNA load was <400 copies/mL in 19 of the 22 (86%) and <50 copies/mL in 15 (68%). At baseline and month 1, 3, 6, 9, and 12 the numbers of patients who had <400 copies/mL HIV-1 RNA were 2 of 23, 16 of 22, 19 of 22, 18 of 22, 12 of 14, 6 of 8, and who had <50 copies/mL were 1 of 23, 5 of 22, 9 of 22, 11 of 22, 7 of 14, 5 of 8. The median genotypic sensitivity score, determined retrospectively at the start of RAL treatment was 2 (range1 to 4) with no or only 1 active PI in 14 cases. The use of ETV and DRV permitted addition of 1 active drug for 13 of 16 patients and 11 of 17, respectively. Median CD4 cell counts increased progressively from 194 cells/mL at baseline to 297, 342, and 402 at month 1, 3, and 6, respectively (p <0.001). In the first adolescents treated in real-life practice with RAL, combined with ETV or DRV in 20 cases, a potent antiretroviral effect and a good safety profile were observed. 

Conclusions:  Despite very long periods of viral replication on previous ART and large spectra of resistance, virological success was obtained for most patients at the last follow-up.