Lopinavir/ritonavir+Tenofovir/Emtricitabine Is Superior to Nevirapine+Tenofovir/Emtricitabine for Women with prior Exposure to Single-dose Nevirapine: A5208 (“OCTANE”)
Shahin Lockman and A5208/OCTANE Study Team
Brigham and Women`s Hosp, Boston, MA, US
Background: Single-dose nevirapine (sdNVP) reduces
mother to child transmission of HIV, but can select for NVP-resistant virus.
Optimal ART for women with prior sdNVP exposure is unknown.
Methods: In 7 African countries, 243 HIV-1-infected
women who had taken intrapartum sdNVP at least 6 months earlier and had
screening CD4 count <200 cells/mm3 were randomized to ART with
tenofovir/emtricitibine (TDF/FTC) and either lopinavir/ritonavir (LPV/r) twice
daily (n = 120) or NVP twice daily (n = 123). The primary endpoint was time
from randomization to either death or confirmed virologic failure (plasma HIV-1
RNA <1 log10 below baseline 12 weeks after treatment initiation,
or ≥400 copies/mL at or after 24 weeks). The primary analysis was
modified intent to treat, excluding 2 women who did not start study treatment.
In October 2008, the DSMB recommended early release of study findings. Data are
included through this date; results are not reported for an ongoing, parallel
trial in 502 women with no prior sdNVP (per DSMB).
Results: At entry, median values were as follows:
age 31 years, CD4 139 cells/mm3, HIV-1 RNA 5.15 log10
copies/mL, time since last sdNVP use 17 months, and duration of follow-up 73
weeks. All women recalled sdNVP use; 73% had written documentation that sdNVP
was provided. Significantly more women in the NVP arm (31, or 26%) than the
LPV/r arm (10, or 8%) reached the primary endpoint (p = 0.0007). Of
these, 36 had virologic failure (27 in NVP, 9 in LPV/r arm); 5 died without
preceding virologic failure (4 in NVP, 1 in LPV/r arm). None of the 5 deaths
were reported to be treatment-related. The difference between the NVP and LPV/r
arms appeared to decrease with increasing time between last sdNVP exposure and
ART initiation. Among women starting ART 6 to <12 months after sdNVP, 15
(37%) and 1 (3%) in the NVP and LPV/r arms, respectively, reached the primary
endpoint, vs 12 (26%) and 6 (12%) when last sdNVP exposure was 12 to < 24
months prior, and 4 (12%) and 3 (10%) when last sdNVP exposure was ≥2
years prior. Baseline genotypes, run retrospectively in 239 women, showed NVP
resistance in 33 (14%; K103N in 28 of 33); of these 33, 11 of 15 (73%) in the
NVP arm reached the primary endpoint vs 1 of 18 (6%) in the LPV/r arm. Among
the 206 women without baseline NVP resistance, 18% (NVP arm) vs 9% (LPV/r arm)
reached the primary endpoint. More women (15, 12%) discontinued NVP due to
adverse events than LPV/r (1, 1%).
Time to virologic failure or to death
Conclusions: LPV/r + TDF/FTC is superior to NVP +
TDF/FTC in women with prior exposure to peripartum sdNVP.