Paper # 912 
Greater Persistence of Drug Resistance Mutations in HIV-1 Subtype C than Other Subtypes among Women Exposed to sdNVP for the PMTCT
Chunfu Yang*1, E Njagi2, J McNicholl3, L Njobvu4, J Ong’ech2, D Potter5, W Ratanasuwan6, O Bolu1, J Johnson1, P Weidle1, and for the NNRTI Response Study Team
1CDC, Atlanta, GA, US; 2Kenyatta Natl Hosp and Univ of Nairobi, Kenya; 3Thailand Ministry of Publ Hlth-US CDC Collaboration, Nonthaburi; 4Ctr for Infectious Disease Res in Zambia, Lusaka; 5CDC Zambia, Lusaka; and 6Siriraj Hosp, Mahidol Univ, Bangkok, Thailand
Background: Single-dose nevirapine (sdNVP) is widely
used for prevention of mother-to-child transmission of HIV-1 (PMTCT), but it often
selects for viral drug resistance mutations in women soon after exposure. As
part of a multi-country study of NNRTI-based ART in Kenya, Thailand, and Zambia, we investigated the effect of HIV-1 subtypes on the persistence of drug
resistance mutations in women exposed to sdNVP for PMTCT.
Methods: We genotyped viral RNA from 330 sdNVP-exposed
women (none of whom received an antiretroviral tail following sdNVP) from Kenya (n = 62), Thailand (n = 86), and Zambia (n = 182) for NNRTI-associated drug resistance
mutations using conventional sequencing encompassing the reverse transcriptase codons
1-251. We used allele-specific real-time polymerase chain reaction (RT-PCR) to
screen for minor strains of NNRTI-associated drug resistance mutations
including K103N, V106M/I, Y181C, and G190A (n = 303). We determined HIV-1
subtypes by phylogenetic analysis and analyzed associations of HIV-1 subtypes
with NNRTI-associated drug resistance mutations at <3, 4 to 6, 7 to 12, and
>12 months since exposure to sdNVP. Fisher’s exact test was used for
statistical analysis and P-value ≤0.05 was considered significant.
Results: Phylogenetic analysis indicated that 181
women were infected with HIV-1 subtypes C, 80 with CRF01_AE, 46 with A, and 23
with other subtypes. The table shows the prevalence of drug resistance
mutations for each test by subtype over time and compares the prevalence of drug
resistance mutations between subtype C and non-subtype C.
|
Months since SDNVP exposure
|
Subtype C
|
Subtype A
|
CRF01-AE
|
Others
|
P value (C vs Non-C)
|
|
No. tested
|
No. with DRM
|
% with DRM
|
No. tested
|
No. with DRM
|
% with DRM
|
No. tested
|
No. with DRM
|
% with DRM
|
No. tested
|
No. with DRM
|
% with DRM
|
|
Conventional Sequencing
Analysis
|
|
<3
|
30
|
17
|
57
|
17
|
4
|
24
|
8
|
6
|
75
|
7
|
3
|
43
|
0.30
|
|
4-6
|
23
|
4
|
17
|
11
|
0
|
0
|
4
|
1
|
25
|
6
|
2
|
33
|
1.00
|
|
7-12
|
40
|
1
|
3
|
12
|
1
|
8
|
4
|
0
|
0
|
5
|
0
|
0
|
1.00
|
|
>12
|
88
|
4
|
4
|
6
|
0
|
0
|
64
|
0
|
0
|
5
|
0
|
0
|
0.12
|
|
Total
|
181
|
26
|
|
46
|
5
|
|
80
|
7
|
|
23
|
5
|
|
0.40
|
|
Allele-specific Real-Time
PCR
|
|
<3
|
28
|
19
|
67
|
16
|
7
|
44
|
8
|
6
|
75
|
6
|
1
|
17
|
0.10
|
|
4-6
|
23
|
11
|
48
|
11
|
2
|
18
|
4
|
0
|
0
|
6
|
2
|
33
|
0.06
|
|
7-12
|
31
|
6
|
19
|
11
|
2
|
18
|
3
|
0
|
0
|
4
|
1
|
25
|
1.00
|
|
>12
|
78
|
18
|
21
|
6
|
0
|
0
|
63
|
1
|
2
|
5
|
0
|
0
|
<0.001
|
|
Total
|
160
|
54
|
|
44
|
11
|
|
78
|
7
|
|
21
|
4
|
|
<0.001
|
Conclusions: Drug resistance mutations were detected
more frequently in subtype C than non-subtype C by allele-specific RT-PCR among
women exposed to sdNVP >1 year prior, suggesting that drug resistance
mutations associated with NNRTI resistance may persist longer in subtype C. Although
conventional sequencing does underestimate the prevalence of drug resistance
mutations among subtype C-infected women exposed to sdNVP, the clinical
consequences of persisting mutations require further study.
|
