Paper # 153LB|
Efficacy of ART with NVP+TDF/FTC vs LPV/r+TDF/FTC among Antiretroviral-naïve Women in Africa: OCTANE Trial 2/ACTG A5208
James McIntyre*1, M Hughes2, J Mellors3, Y Zheng2, J Hakim4, A Asmelash5, F Conradie6, R Schooley7, J Currier8, S Lockman2,5,9, and A5208/OCTANE Study Team
1Chris Hani Baragwanath Hosp, Johannesburg, South Africa; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Univ of Pittsburgh Med Ctr, PA, US; 4Univ of Zimbabwe, Harare; 5Botswana-Harvard AIDS Inst, Gaborone; 6Univ of the Witwatersrand, Johannesburg, South Africa; 7Univ of California, San Diego, US; 8Univ of California, Los Angeles, US; and 9Brigham and Women`s Hosp, Boston, MA, US
Background: OCTANE Trial 1 showed that nevirapine (NVP)+tenofovir/emtricitabine
(TDF/FTC) was inferior to lopinavir/ritonavir (LPV/r) + TDF/FTC as initial ART
among women with prior single dose NVP (sdNVP) exposure. The current study (OCTANE Trial 2) compared the same
regimens as initial ART among women with no prior sdNVP.
Methods: In 7 African countries, 500 ARV-naïve HIV-infected
women with CD4<200 cells/mm3 and no prior sdNVP were randomized
to initiate open-label ART with TDF/FTC once daily and either NVP (n = 249)
or LPV/r (n = 251) twice daily. Women were followed for >48
weeks. The primary endpoint was time from randomization to either death or
confirmed virologic failure (VF: plasma HIV RNA<1 log10 below
baseline 12 weeks after treatment initiation, or >400 copies/mL at or
after 24 weeks) in intent to treat analysis. Trial 2 was designed to assess
equivalence (defined as 95%CI for the hazard ratio [HR]: 0.5 to 2.0).
Results: Baseline characteristics (medians) were: age = 34
years, CD4 = 121 cells/mm3, HIV RNA = 5.15 log10
copies/mL. Median duration of follow-up was 118 weeks; 29 (5.8%) women were
lost to follow-up. Overall, 42 (17%) women in the NVP arm and 50 (20%) in the
LPV/r arm reached the primary endpoint (HR = 0.85, 95%CI 0.56 to 1.29); results
of as-treated analysis were similar (HR = 0.71, 95%CI 0.45 to 1.13). At 48
weeks, the proportions alive without VF were 85.7% and 86.3% for the NVP and LPV/r
arms (difference 0.6%, 95%CI -5.5% to 6.8%).
Of the 92 women reaching an
endpoint, 80 had VF (37 in NVP, 43 in LPV/r arm) and 12 died (5 in NVP, 7 in
LPV/r arm). Grade 3 or 4 signs/symptoms while taking assigned NVP or LPV/r were
reported in 75 (15%) women (14% in NVP, 16% in LPV/r arm), and 26% and 22%
(respectively) had Grade 3/4 laboratory test abnormalities. However, 35 women
in the NVP vs. none in the LPV/r arm stopped ART due to an adverse event (P <0.001),
most in the first 8 weeks. VF, death or permanent treatment discontinuation
occurred in 32% in NVP and 22% of LPV/r arms (HR = 1.68, 95%CI 1.18 to 2.40).
Conclusions: Initial ART with NVP + TDF/FTC had equivalent
virologic efficacy compared with LPV/r+TDF/FTC in treatment-naïve women with CD4 <200
cells/mm3 and no prior sdNVP exposure. However, treatment
discontinuation due to adverse events was more frequent with NVP. These
findings support the current use of NVP for initial ART regimens with careful
monitoring. Previously-reported inferiority of NVP (vs. LPV/r) in OCTANE Trial
1 was likely related to NVP resistance from prior sdNVP exposure.