Use of T-20 at the end of pregnancy to a multi-treated HIV-infected woman with virological breakthrough

A research letter in the 24 September edition of AIDS describes a French case of a treatment experienced pregnant woman with virological breakthrough treated with enfuvirtide during the last three weeks of her pregnancy.

The 38 year old HIV positive woman became pregnant in January 2003 while receiving an antiretroviral regimen of 3TC, tenofovir and lopinavir/ritonavir (Kaletra). Her CD4 count was 365cells/mm³ and she had a viral load of 40,522 copies/mL.

The patient was diagnosed in 1990 and treated with zidovudine monotherapy in 1994 (her lowest CD4 cell count of 25 cells/mm³ was recorded in May 1995) to which 3TC was added in 1995, and indinavir in 1996.

Her CD4 cell count was stable at 300 cells/mm³ on this regimen, but her viral load remained detectable. Her treatment was changed to d4T, ddI, ritonavir, and saquinavir (Invirase) in 1997 and switched again to d4T, 3TC and efavirenz in 1999 due to lipodystrophy. In August 2001, after virological breakthrough she was again switched to another regimen of 3TC, tenofovir and lopinavir/ritonavir. She became pregnant on this regimen.

She received a genotype resistance test in August 2003, at which time her viral load was 32,961 copies/mL. The test results found her to be resistant to both nucleoside reverse transcriptase inhibitors and protease inhibitors but sensitive to non nucleoside reverse transcriptase inhibitors. Mutations were found at M41L, E44D, D67N, M184V, L210W and T215Y, indicating resistance to AZT, 3TC, ddI, d4T and abacavir and possible resistance to tenofovir. And at L10F, K20R, M36I, M46L, I54V, L63P, A71V, V82A, I84V and L90M, conferring resistance to all protease inhibitors.

Enfuvirtide and nevirapine were added to her regimen of 3TC, tenofovir and lopinavir/ritonavir three weeks before an elective Caesarean section was performed, and on 10 September 2003 she gave birth to a healthy baby girl.

The neonate was treated at birth with AZT, 3TC and nevirapine, and was PCR negative at day 3, and 1, 3 and 6 months. At the time of delivery, the mother’s viral load was 57 copies/mL and her CD4 cell count was 549 cells/mm³ (16.8%).

The investigators write: “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 maternofoetal HIV transmission.”

comment

The first report of T-20 in pregnancy confirms that the introduction of two classes of therapy to which HIV is sensitive effectively reduces viral load. This is known to be associated with a reduced risk of transmission.

Treatment appears to have been deferred to late in pregnancy to minimise the risk of further virological rebound before delivery. Little comment can be made on the safety of T-20 in this setting.

Meyohasa MC, Lacombea K, Carbonneb, B, et al. Enfuvitide prescription at the end of pregnancy to a multi-treated HIV-infected woman with virological breakthrough. AIDS 2004, Vol 18 No 14. Research letters 1966.