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Emergence of Genotypic Resistance in HIV-1-infected Pregnant Women Taking HAART to Reduce Mother-to-child Transmission of HIV-1
F Lyons*1, S Coughlan2, C Byrne2, S Hopkins1, W Hall2, C Bergin1, and F Mulcahy1
1St. James's Hosp., Dublin, Ireland and 2UCD, Belfield, Dublin 4, Ireland
Background: Antenatal antiretroviral therapy (ART) reduces mother-to-child transmission. Concerns
for emergence of resistance have prompted a change from mono and dual therapy
in reducing mother-to-child transmission. In women not requiring HAART for their
own health, the effect of antenatal HAART on emergence of viral resistance is
unknown.
Methods: Pregnant HIV-1-infected women with a
pre-treatment CD4 >300x106/L were prescribed HAART from the third
trimester and discontinued therapy postpartum (n = 40). All women were counseled on the importance of adherence to
therapy. Those taking regimens including NVP staggered HAART cessation for
pharmacokinetic reasons. Genotypic resistance testing (RT) (HIV-1 TruGene) was
performed after HAART cessation and
on pretreatment samples when postpartum samples showed primary mutations.
Samples with viral load >500 copies/mL were included in analysis.
Statistical analysis was performed using SPSS
12.0.
Results: Of 40 women, 30 (75%) were from sub-Saharan Africa; 32 (80%) had sequences available for analysis; 8
were excluded (6 had a viral load <500 and 2 had no sequence). Of the
remaining 32 women, 2 (6.2%) had taken ART
during a previous pregnancy (1 ZDV, and 1 combivir), and 30 (94%) were ART naïve. Pre-treatment parameters were: median CD4 = 419x106/L (300 to 1082);
median viral load 2851 copies/mL (50 to 34,753). HAART regimens were: combivir/NVP (27), combivir/NLF (4),
DDI/ZDV/NLF (1). Median duration of HAART was 66 days (3 to 110). Viral load
around the time of delivery for 20 of the 32 women (62%) was <50 copies/mL; for
25 (75%) <1000 copies/mL; for 6 (16%), no result because they delivered
early (5) or failed to attend (1); for 1 (3%) >1000 copies/mL (12,778).
Median time from HAART cessation to RT = 48 days (13 to 198). Of the 32
postpartum sequences 22 (69%) were non-B subtype, 10 (31%) were B subtype. There
were 7 primary mutations (V106A(1), Y181C(2), G190A(1), K101E(1), M184V(1),
T215S(1) were detected in 5 (16%) women. All 5 were on regimens including NVP and
were ART naïve; 4 of them had no
mutations detectable pre-treatment (1 pre-treatment RT not available, viral
load, 83 copies/mL). Viral load was similar in those that developed resistance
and those that did not: baseline viral
load (p = 0.48), baseline CD4 (p = 0.55), duration of therapy (p = 0.67), and delivery viral load (p = 0.08).
Conclusions: In
this cohort 16% of women demonstrated primary genotypic resistance postpartum
despite HAART. Pre-treatment parameters, duration of therapy and response to
therapy did not predict emergence of mutations. The effect of these mutations
on future ART response and
management of future pregnancies remains to be observed.
Keywords: HAART; resistance; pregnancy
