Primary resistance in the RT connection and RNase H domains in
different HIV-1 subtypes
A.F. Santos1, C.P. Muniz1, L.R. Goés2, J. Silveira3, A.M.B. Martinez3, U. Tupinambás4, D. Greco4, M.A. Soares2,5
1Universidade Federal do Rio de Janeiro, Departamento de Genética, Rio de Janeiro, Brazil, 2Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 3Fundação Universitaria do Rio Grande, Rio Grande, Brazil, 4Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, 5Instituto Nacional de Câncer, Rio de Janeiro, Brazil
Background: Mutations in HIV-1 RT
C-terminal domains, connection and RNase H, have been shown to play an
important role in resistance to RT inhibitors. In Brazil, the rate of primary
resistance in PR and RT polymerase domain is below 10%. Here we evaluate the
primary resistance in connection and RNase H domains and compared the presence
of primary mutations in diverse HIV-1 subtypes.
hundred twenty-nine treatment-naïve patients recently diagnosed for HIV-1 were
screened in 1,454 naïve-treatment isolates of five HIV-1 subtypes obtained from
the infection (2007-8) in Southern Brazil had
their viral RNA isolated from plasma and retrotranscribed. Nested PCR amplified
the genomic regions corresponding to RT connection and RNase H. Products were
sequenced and subtyped by phylogenetic analysis. All drug resistance mutations (DRM)
considered here had their phenotypic role in resistance determined in recent
studies: N348I, A360V, T369V, A371V, I506L, Q509L and Q547K. DRM Stanford
Database: subtype A (138), B (442), C (495), CRF01_AE (166) and CRF02_AG (213).
Chi-square tests were conducted to compare the frequency of each DRM across subtypes
with that of subtype B.
Results: Of 129
isolates, nine (6.9%) presented at least one RT C-terminal mutation. The
mutation A371V was found in 4.5% of patients, followed by T369V (2.3%), Q547K
(1.9%) and I506L (0.9%). The mutation A371V was shown as a genetic signature of
subtype A, CRF01_AE and CRF02_AG. Interestingly, T369Vwas present in 20% of
CRF02_AG isolates, while its presence in other subtypes was below 6%
(p< 0.001), and is considered a major DRM to nevirapine in subtype B.
Conclusions: This study is the
first to detect DRM in HIV-1 RT connection and RNase H regions from
naïve-treatment patients. Some DRM in these domains presented distinct
proportion in different HIV-1 subtypes. We recommend the inclusion of these
mutations in resistance surveillance protocols.
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