Lopinavir-based regimen may be superior to nevirapine-based regimen for some peripartum women

Lockman S. N Engl J Med. 2010;363:1499-1509.

Women with HIV who have prior exposure to single-dose nevirapine may be treated more effectively at treatment initiation with a lopinavir-based antiretroviral therapy regimen than with a nevirapine-based regimen, according to study results.

Researchers from several sites in the US and Africa conducted the Optimal Combination Therapy After Nevirapine Exposure (OCTANE) trials in women from seven African countries. Trial 1 involved 243 women who had previously received single-dose nevirapine, and trial 2 involved 502 women without prior nevirapine exposure.

The current report provides comprehensive findings for trial 1 and primary endpoint findings for trial 2.

Trial 1 results

The final analysis in trial 1 involved 241 women with HIV who had T-cell counts less than 200 cells/mm³ and who had or had not taken single-dose nevirapine at least 6 months before enrollment. Participants were randomly assigned to ART with tenofovir-emtricitabine (Truvada, Gilead) plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir.

The primary outcome measure was the time to confirmed virologic failure — defined as confirmed HIV RNA level less than 1 log₁₀ copy per milliliter less than baseline at 12 weeks after treatment initiation or a confirmed HIV RNA level that was 400 log₁₀ copies or more per milliliter 24 weeks or more after treatment was begun — or death. Follow-up was conducted for a median of 74 weeks.

There were 121 women in the nevirapine arm and 120 women in the ritonavir-boosted lopinavir arm.

The primary endpoints were reached by significantly more women taking nevirapine than women taking ritonavir-boosted lopinavir, 26% vs. 8% (adjusted P=.001).

There were 28 virologic failures and four deaths in the nevirapine arm, compared with one death and nine virologic failures in the ritonavir-boosted lopinavir arm.

Differences between the two groups may have decreased as the interval between exposure to single-dose nevirapine and ART initiation increased, according to the results.

Among 239 women tested using retrospective bulk sequencing of baseline plasma samples, 14% demonstrated signs of nevirapine resistance.

Trial 2 results

Among the 500 women who did not have prior nevirapine exposure, 249 received the nevirapine regimen and 251 received the ritonavir regimen.

Virologic failure or death was experienced by 14% of women in both groups.

In the nevirapine group, there were 29 virologic failures and five deaths, and in the ritonavir group, there were 32 virologic failures and four deaths.

“There was significant evidence that the difference in the efficacy of the randomized treatments varied between trial 1 and trial 2 (P=.002 for interaction between study treatment and trial),” the researchers wrote.

The researchers concluded that ritonavir-boosted lopinavir plus tenofovir-emtricitabine is preferable to nevirapine plus tenofovir-emtricitabine for treating women with previous single-dose nevirapine exposure, but not in women without prior exposure.

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