Pregnancy-limited HIV antiretroviral therapy promotes drug resistance

[John2038]

HIV-infected women who take antiretroviral drugs for the first time when they become pregnant and discontinue them after delivery are likely to develop antiretroviral resistance, new research suggests.

"The main determinants of resistance selection during pregnancy were the characteristics of the antiretroviral regimen chosen to prevent mother-to-child transmission," the investigators report in the January 2nd issue of AIDS.

Led by Dr. Ruth E. Tuomala from Harvard Medical School in Boston, the researchers evaluated resistance data from 114 antiretroviral-naive, HIV-infected pregnant women in the U.S. who received pregnancy-limited antiretroviral therapy between 1998 and 2004.

The women were treated with zidovudine and lamivudine; 64% also received nelfinavir and 7% received nevirapine. All had 2- or 6-month postpartum plasma samples with HIV RNA levels > 500 copies/mL.

Using allele-specific PCR, the researchers tested for the M184V mutation, associated with high-level resistance to lamivudine and emtricitabine; K103N, associated with resistance to nevirapine and efavirenz; and D30N, associated with resistance to nelfinavir.

Their tests showed that the postpartum rate of single-class resistance was 63.2%. Rates of dual- and triple-class resistance were 10.5% and 1.7%, respectively.

On multivariate analysis, selection of M184V was significantly associated with exposure to dual versus triple-drug therapy (OR 19.64, p < 0.01), and duration of zidovudine exposure (OR 1.29 per additional month, p = 0.03).

Selection of K103N was linked with nevirapine use (OR 9.75, p = 0.01) and length of exposure to zidovudine plus lamivudine (OR 1.46 per additional month, p = 0.02).

Neither the presence of resistance mutations before antiretroviral therapy, nor the first prenatal CD4+ cell count, nor use of hard drugs or alcohol were associated with postpartum detection of the K103N or M184V mutations.

The researchers suggest that "triple-drug therapy should be the preferred mother-to-child transmission prevention approach to preserve future treatment options for others."

Finally, they add, resistance mutations selected during pregnancy are likely to wane over time, so "performing postpartum genotypic resistance testing within 1 to 2 months after delivery would be highly informative for designing future treatment regimens for women exposed to pregnancy-limited antiretroviral therapy and may be useful in guiding the choice of antiretroviral regimen postpartum."

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