T-20 fails to prevent mother-to-child transmission: case report

Doctors from San Francisco have reported a case of mother-to-child transmission of multidrug-resistant HIV via vaginal delivery despite an undetectable blood plasma viral load. The report's authors, from the University of California, San Francisco, believe that this may have been due to the limited genital tract penetration of the only active drug in the mother's regimen, T-20 (enfuvirtide, Fuzeon). The case report appears as a letter in the 10^th June issue of the journal, AIDS.

The mother, 36, who had been pregnant eight times and had two children, was seven weeks into an unplanned-but-wanted pregnancy when she presented at the clinic. At the time, she was receiving 3TC (lamivudine, Epivir), abacavir (Ziagen), and lopinavir/ritonavir (Kaletra), and had a viral load of 29,712 copies/ml and a CD4 cell count of 323 cells/mm³.

Due to a long and chequered HIV treatment history the woman had taken most nucleoside analogues, at least one non-nucleoside reverse transcriptase inhibitor and at least two protease inhibitors. Genotypic resistance testing revealed multidrug resistance (reverse transcriptase: M41L, L74V, K103N, M184V, and T215Y; protease: L10F, L33F, I54V, L63P, A71V, V82A, I84V). High level resistance to most drugs was confirmed by phenotypic resistance testing.

At week 33 of her pregnancy, the mother was admitted to hospital for directly observed therapy (DOT) and her regimen was changed to 3TC, abacavir, tenofovir (Viread), Kaletra, and T-20. When labour was induced at 37 weeks, the mother's blood plasma viral load was undetectable. Intravenous AZT (zidovudine, Retrovir) was administered during labour, and the baby received AZT, 3TC, Kaletra and nevirapine (Viramune) after delivery.

Although polymerase chain reaction (PCR) testing at birth was indeterminate, the baby's blood plasma viral load was 6240 copies/ml at the age of eight days. Genotypic resistance testing revealed the presence of multiple protease and reverse transcriptase resistance mutations but the absence of any mutations known to confer resistance to T-20.

The authors note that this is the first time that they have been unable to prevent mother-to-child transmission in their clinic since the introduction of highly active antiretroviral therapy (HAART) in 1995, even though many mothers have had evidence of drug resistant HIV.

There are limited data regarding the use of T-20 in pregnancy, although the authors note that "its ability to suppress multidrug-resistant HIV-1 should make it an ideal candidate for preventing perinatal transmission." The authors point out, however, that "its activity in other compartments remains undefined."

Although maternal blood plasma load is a strong predictor of mother-to-child transmission, it is also known that the maternal genital tract viral load is an independent correlate of HIV transmission. "Theoretically," they write, "ongoing viral replication of the multidrug-resistant, enfuvirtide-susceptible virus may have occurred within the genital compartment, leading to transmission at delivery."

They note that it is possible that transmission occurred before the mother began her T-20-based regimen, although the indeterminate RNA at birth, with rapidly increasing viral load eight days later, suggests transmission at delivery.

The authors conclude by saying that "we believe that the use of a regimen in which the only fully effective drug may have limited ability to penetrate the genital compartment played a critical role [in the transmission of HIV from mother to child during vaginal delivery]. As the role of the genital compartment in perinatal transmission becomes further elucidated, decisions regarding the preferred delivery route may be guided by genital viral load measurements, and, as suggested here, knowledge of the relative capacity of a given drug regimen to penetrate the genital compartment.

"Testing these hypotheses will require longitudinal assessments of HIV-1 in multiple compartments in patients receiving salvage regimens that contain enfuvirtide."