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Antiretroviral Drug Resistance among Drug-naive HIV-1 Recently Infected Individuals in South Africa
Visva Pillay*1, J Ledwaba1, G Hunt1, M Rakgotho1, B Singh1, L Makubalo2, A Puren1, and L Morris1
1Natl Inst for Communicable Diseases, Johannesburg, South Africa and 2Dept of Hlth, South Africa
Background: Surveillance for transmitted HIV-1 drug resistance was
conducted among drug-naïve, recently infected subjects in South Africa,
where single-dose nevirapine (NVP) has been in use since
2002 and a treatment program started in 2004.
Methods: All subjects were from the Gauteng Province
and were part of the 2002 and 2004 annual ante-natal HIV seroprevalence survey
conducted by the South African National Department of Health. All subjects met
the inclusion criteria as set out by the WHO guidelines for HIV-1 transmitted
drug resistance surveillance (women <21 years of age and in first pregnancy).
Genotyping was performed on plasma viral RNA by sequencing the protease and
reverse transcriptase genes. Samples were also tested for the K103N mutation using
a highly sensitive allele-specific real time polymerase chain reaction (PCR) assay
(ASC-PCR).
Results: Of 151 eligible participants from 2002, 66 (44%) were
successfully amplified. None of the samples from 2002 had evidence of resistance
mutations on genotyping or by ASC-PCR. Of 163 eligible participants from 2004,
60 (37%) samples were successfully amplified. Of these, 4 (2.5%) had K103N by
genotyping, 1 of which also contained the M184V mutation and a further 2 had
the K70R or T69D resistance mutations. In total, 6 (3.7%) participants showed
evidence of resistance mutations on genotyping. All samples clustered
phylogenetically with HIV-1 subtype C, the predominant subtype circulating in South Africa. By
ASC-PCR, 5 samples (3.1%) were positive for K103N including the 4 that were
genotype positive.
Conclusions: The K103N ASC-PCR may represent a suitable screening method
for drug-resistance surveillance as this mutation is commonly selected by NVP and
can persist for extended periods in untreated persons. These data suggest that
resistant variants may be circulating at a low frequency in South Africa
and that annual surveillance among untreated populations should be conducted to
determine whether this increases with time.
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