Adding Single-dose Tenofovir (Viread) plus Emtricitabine (Emtriva) Lowers the Risk of Drug Resistance in Pregnant Women Receiving Nevirapine to Prevent Perinatal HIV Transmission

	HIV and AIDS MAIN SECTION 1

By Liz Highleyman

In developed countries, HIV positive pregnant women are advised to receive 3-drug combination antiretroviral therapy if appropriate, or at least AZT (zidovudine, Retrovir) during pregnancy and delivery to prevent mother-to-child HIV transmission.

However, such intensive treatment is often not available in resource-limited settings, where many pregnant women and their infants receive only a single dose of nevirapine (Viramune) to prevent perinatal transmission. This intervention reduces transmission risk by about 40%, but often -- 20%-70% of the time in various studies -- causes the mother to develop resistance to nevirapine, and with it cross-resistance to the entire class of first-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs). This could potentially compromise her own later treatment and the effectiveness of prophylaxis during subsequent pregnancies, although studies have shown that nevirapine resistance tends to diminish within 6 months after receiving the single dose.

HIV is less able to develop resistance when multiple drugs are used together. As reported in the November 6, 2007, advance online edition of The Lancet, researchers conducted a study in Zambia to assess whether adding a single dose of tenofovir (Viread) plus emtricitabine (Emtriva) -- the 2 drugs in the Truvada combination pill -- could reduce the emergence of resistance.

The study included 400 HIV-infected pregnant women who sought care at 2 public primary health facilities in Lusaka, Zambia between 2005 and 2007. All were offered short-course AZT (starting at week 32 of pregnancy) and single-dose nevirapine at the onset of labor according to the local standard of care. In addition, half were randomly assigned to also receive a single oral dose of 300 mg tenofovir plus 200 mg emtricitabine during labor, while the rest received no additional therapy. (Women who required combination antiretroviral therapy for their own care were referred for treatment and not enrolled in the study.)

Results

• Of the 200 women who received tenofovir/emtricitabine, 14 were lost to follow-up or withdrew from the study, 2 did not take study drug according to protocol, and 1 specimen was lost; in the control group, 23 women were lost to follow-up or withdrew from the study, and 3 specimens were lost.

• The mother-to-child HIV transmission rate was similar in both arms: 6% in the tenofovir/emtricitabine group vs 8% in the control group.

• Women who received tenofovir/emtricitabine had a lower viral load 2 weeks after delivery (63% vs 53%, respectively, < 400 copies/mL), but the difference disappeared by week 6.

• Women who received single-dose tenofovir/emtricitabine were 73% less likely than those in the control group to have mutations that conferred NNRTI resistance 2 weeks after delivery, and 53% less likely 6 weeks after delivery (12% vs 25%; risk ratio [RR] 0.47).

• Tenofovir/emtricitabine offered the most benefit in terms of reduced resistance among women with higher HIV viral loads (> 10,000 copies/mL).

• The most common serious adverse event was postpartum anemia (a potential side effect of AZT), which occurred in 4 women in each group.

• 10% infants in the tenofovir/emtricitabine group and 12% in the control group had a serious adverse event -- mostly septicemia (n=22) or pneumonia (n=8) -- but these did not differ between the groups, and none were judged to be due to the study drugs.

Conclusion

Based on these findings, the authors concluded, "A single dose of tenofovir and emtricitabine at delivery reduced resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery by half; therefore this treatment should be considered as an adjuvant to intrapartum nevirapine."

In an accompanying editorial, Shahin Lockman and James McIntrye of the Harvard School of Public Health wrote that the results of the Zambia study "provide strong evidence" that adding single-dose tenofovir/emtricitabine to the standard intervention for perinatal prevention is "a new, effective, and feasible approach" to reducing maternal nevirapine resistance and "should be seriously considered for implementation."

Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Schools of Medicine and Public Health, University of Alabama, Birmingham, AL; Catholic Medical Missions Board, Lusaka, Zambia; Saban Research Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA; University Teaching Hospital, Lusaka, Zambia; Elizabeth Glaser Pediatric AIDS Foundation, Santa Monica, CA.

11/16/07

References

BH Chi, M Sinkala, F Mbewe, and others. Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial. The Lancet. November 6, 2007 [Epub ahead of print].

S Lockman and JA McIntyre. Reduction of HIV-1 drug resistance after intrapartum single-dose nevirapine. The Lancet. November 6, 2007 [Epub ahead of print].

FDA-Approved Treatments
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