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Fuzeon Used To Prevent Mother-To-Child-Transmission of HIV
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"Enfuvirtide prescription at the end of pregnancy to a multi-treated HIV-infected woman with virological breakthrough"
AIDS: Volume 18(14) 24 September 2004
Meyohas, Marie-Carolinea; Lacombe, Karinea; Carbonne, Brunob; Morand-Joubert, Laurencec; Girard, Pierre- Mariea
Departments of aInfectious Diseases, bObstetrics and Gynecology, and cMicrobiology, Centre hospitalo-universitaire de Saint-Antoine, AP-HP, Paris VI, France.
Antiretroviral therapy has drastically reduced the risk of materno-fetal HIV transmission, which is strongly dependent on maternal viral load in late pregnancy. Conception during three-drug antiretroviral treatment has become more frequent in recent years, and the choice of an efficient treatment might be challenging in multi-treated pregnant women presenting with a highly mutated virus.
Enfuvirtide, a 36-amino acid peptide, is a recently marketed HIV cell fusion inhibitor. It is indicated in patients infected by a multi-resistant HIV strain, but data about its efficacy in reducing materno-fetal transmission are scarce.
In January 2003, a 38-year-old woman diagnosed with HIV infection in 1990 became pregnant when in virological breakthrough on lamivudine, tenofovir and lopinavir boosted by ritonavir. The CD4 cell count and HIV-1-RNA load were 365 cells/mm3 and 40,522 copies/ml, respectively. She had a history of recurrent oral and vaginal candidiasis and genital herpes. The lowest CD4 cell count was recorded in May 1995 (25 cells/mm3). She was initially treated with zidovudine in 1994, lamivudine was added in 1995, and Indinavir in 1996. The CD4 cell count was stable at 300 cells/mm3 on this treatment, but the viral load remained detectable.
The patient was prescribed a new antiretroviral regimen containing stavudine, didanosine, ritonavir and saquinavir in 1997, which was switched to stavudine, lamivudine and efavirenz in 1999 after the onset of lipodystrophy.
In August 2001, after a new virological breakthrough and the detection of resistance to non-nucleoside reverse transcriptase inhibitors (Y181C mutation), she was again switched to another regimen associating lamivudine, tenofovir and lopinavir boosted by ritonavir. She became pregnant when on this treatment (last period 22 December 2002). Resistance genotyping was performed on 6 August 2003. At this time, the viral load was 32 961 copies/ml. The reverse transcriptase gene bore the M41L, E44D, D67N, M184V, L210W and T215Y mutations, conferring resistance to zidovudine, lamivudine, didanosine, stavudine and abacavir, with possible resistance to tenofovir. No mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors were found. The protease gene bore the L10F, K20R, M36I, M46L, I54V, L63P, A71V, V82A, I84V and L90M mutations, conferring resistance to all protease inhibitors.
Therefore, according to the last Agence Nationale de Recherche sur le Sida, France, resistance algorithm published in July 2003, there was a resistance to all the drugs of the two major groups of antiretroviral molecules.
An attempt was made to prevent mother-to-child transmission of HIV by adding enfuvirtide and nevirapine to the existing regimen 3 weeks before elective caesarean section. The patient thus received a combination of lopinavir/ritonavir (boosted with 100 mg ritonavir twice a day), tenofovir, lamivudine, nevirapine and enfuvirtide (90 mg twice a day) given subcutaneously. The only adverse effects noted after the onset of this new regimen were local reactions at the sites of enfuvirtide injections.
On 10 September 2003 the patient gave birth to a healthy baby girl weighing 2.9 kg. The infant was treated at birth with zidovudine, lamivudine and nevirapine, and was HIV-1 polymerase chain reaction-negative at day 3, and months 1, 3 and 6. At delivery, the mother's viral load was 57 copies/ml and her CD4 cell count was 549 cells/mm3 (16.8%).
This is the first reported use of enfuvirtide during pregnancy in a patient with virological breakthrough. The HIV viral load was reduced to less than 400 copies/ml at the time of delivery, with no adverse effects in the mother or in the child (up to age 6 months). Despite the very limited experience with enfuvirtide in pregnancy, this case shows the potential value of this fusion inhibitor in preventing materno-fetal HIV transmission.
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