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Effectiveness of NNRTI-containing ART in Women Previously Exposed to a Single Dose of Nevirapine: A Multi-country Cohort Study
Paul Weidle*1, J Stringer2, M McConnell1,3, J Kiarie4, T Anekthananon5, T Jariyasethpong6, D Potter2, W Mutsotso7, C Borkowf1, O Bolu1, and The NNRTI Response Study Team
1CDC, Atlanta, GA, US; 2Univ of Alabama at Birmingham, Ctr for Infectious Disease Res in Zambia, Lusaka; 3Thailand Ministry of Publ Hlth-US CDC Collaboration, Nonthaburi; 4Kenyatta Natl Hosp, Univ of Nairobi, Kenya; 5Siriraj Hosp., Mahidol Univ., Bangkok, Thailand; 6Rajavithi Hosp, Bangkok, Thailand; and 7CDC Kenya, Nairobi
Background: Maternal-infant single-dose nevirapine
(NVP) reduces perinatal HIV transmission, but induces viral resistance to NNRTI
drugs in some women. Prior single-dose NVP exposure may compromise future
maternal treatment with NNRTI-based ART.
Methods: Between May 2005 and January 2007, we
enrolled single-dose NVP-exposed and unexposed women starting NNRTI-based ART
in a prospective cohort study in Zambia, Thailand, and Kenya. Women were frequency matched at entry by World Health Organization (WHO) stage and CD4 cell
count. We compared treatment failure (viral load ≥400 copies/mL, not on
NNRTI, died) between exposure groups at 6 months after ART initiation.
Results: We studied 878 women (355 single-dose NVP-exposed,
523 unexposed). Single-dose NVP-exposed women were younger (29 vs 33 years, p
<0.001), had a higher median CD4 (160 vs 139 cells/mm3 p =
0.007), and lower median viral load (97,300 vs 142,000 copies/mL, p = 0.02),
but were of similar weight (51 vs 52 kg, p = 0.4). At 6 months after ART
initiation, 186 (21%) women had failed (76 had viral load ≥400 copies/mL,
51 discontinued the study, 48 died, and 11 had been changed to a protease
inhibitor). Women with exposure to single-dose NVP ≤6 months before
NNRTI-based ART initiation, with baseline CD4 0 to 49 cells/mm3, or viral
load >100,000 copies/mL had poorer treatment responses (see the table).
Women exposed to single-dose NVP >12 months before NNRTI-based ART did as
well as unexposed women. In a secondary analysis including only those still on
NNRTI-based ART at 6 months, we found similar results.
Baseline co-variates
|
n
|
Multivariate odds ratio
for treatment failure at
6 months adjusted for age
|
CI95
|
|
Time since
single-dose NVP
exposure (months)
|
Unexposed
≤6
7 to 12
>12
|
523
115
67
173
|
1.0
1.86
1.61
0.90
|
1.12 to 3.09
0.87 to 2.98
0.56 to 1.45
|
|
Country
|
Thailand
Zambia
Kenya
|
217
509
152
|
1.0
2.00
1.47
|
1.23 to 3.23
0.81 to 2.65
|
|
CD4
(cells/mm3)
|
≥200
50 to 199
0 to 49
|
255
479
144
|
1.0
1.42
3.21
|
0.91 to 2.21
1.88 to 5.49
|
|
Viral load
(copies/mL)
|
<10,000
10,000 to 99,999
≥100,000
Missing
|
114
296
462
6
|
1.0
1.86
2.25
.
|
0.95 to 3.62
1.17 to 4.29
|
|
WHO Stage
|
I/II
III
IV
|
416
358
104
|
1.0
1.42
1.65
|
0.95 to 2.10
0.96 to 2.84
|
Conclusions: A high proportion (79%) of women in
this cohort responded to 6 months of NNRTI-based ART, whether previously
exposed to single-dose NVP or not. These data do suggest an increased risk of
treatment failure among women with recent single-dose NVP exposure, but not
with single-dose NVP exposure >12 months before initiation of NNRTI-based
ART. Treatment with ART or perinatal HIV prevention strategies other than single-dose
NVP should be considered for pregnant women who are likely to initiate ART
within 1 year after delivery.
|
