NEW YORK (Reuters Health) – Intra-partum nevirapine, given to prevent HIV transmission, contributes to HIV resistance mutations to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) – but a one-month postpartum course of zidovudine plus didanosine helps avoid this problem.

That’s according to results of the multicenter, open-label HIV Prevention and Treatment (PHPT)-4 trial, conducted in Thailand and reported in Clinical Infectious Diseases for March 15.

Third-trimester zidovudine and a single intra-partum dose of nevirapine are used to prevent vertical HIV transmission in resource-limited settings, lead author Dr. Marc Lallemant, from Chiang Mai University, and the study team explain.

Because blood levels of nevirapine remain elevated for weeks following the single dose, this regimen tends to select for NNRTI mutations, decreasing efficacy of subsequent NNRTI-based antiretroviral regimens. The authors theorized that by suppressing viral replication, an additional 1-month postpartum course of zidovudine/didanosine would prevent selection of resistance mutations in mothers.

The trial included 222 HIV-infected pregnant women with CD4 cell counts > 250 cells/mm3 who did not require highly active antiretroviral treatment. Enrollment began in 2005.

The women took 300 mg zidovudine twice daily starting at 28 weeks’ gestation. During labor they received 300 mg zidovudine every 3 hours, plus a single dose of nevirapine 200 mg and didanosine 400 mg. Following delivery, they took zidovudine 200 or 300 mg as well as didanosine 250 or 400 mg once daily for 1 month.

The authors compared NNRTI mutation outcomes with those in 222 women from an earlier trial (2001-2003) who had been treated with antepartum zidovudine and intra-partum nevirapine only. Women in the two trials were matched on CD4 cell count, antepartum zidovudine duration and plasma viral load.

Two different mutation assays, performed within 4 months of delivery, identified new postpartum NNRTI resistance mutations in 4 women (1.8%) in the study group and in 46 controls (20.7%) (p < 0.001), a 91% reduction. “The 1-month postpartum regimen appeared to be safe, well tolerated, and easy to adhere to,” the investigators report. They note that preliminary results from another study suggest that a more potent postpartum regimen of lopinavir, zidovudine, and didanosine, of shorter duration, may have similar efficacy. “Interventions to eliminate post-exposure selection of nevirapine resistance are critical to safeguard a highly efficacious intervention for the prevention of mother-to-child transmission while preserving the mother’s future therapeutic options,” Dr. Lallemant and colleagues conclude. A commentary by Dr. Mark F. Cotton and associates at Stellenbosch University, Tygerberg, South Africa points out that the study does not answer the question of how to protect HIV-infected infants from developing NNRTI resistance, both from single-dose nevirapine and more prolonged exposure to nevirapine during breast-feeding. Furthermore, Dr. Cotton and his colleagues add, “This strategy needs to be replicated in Africa, where HIV-1 subtype C has a higher propensity to NNRTI resistance and where women may be sicker.” Reference:
Clin Infect Dis 2010.