Article

Transmission of HIV-1 Drug-Resistant Variants: Prevalence and Effect on Treatment Outcome

Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark.
Clinical Infectious Diseases (Impact Factor: 9.42). 02/2010; 50(4):566-73. DOI: 10.1086/650001
Source: PubMed

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) drug resistance is an important threat to the overall success of antiretroviral therapy (ART). Because of the limited sensitivity of commercial assays, transmitted drug resistance (TDR) may be underestimated; thus, the effect that TDR has on treatment outcome needs to be investigated. The objective of this study was to investigate the prevalence of TDR in HIV-infected patients and to evaluate the significance of TDR with respect to treatment outcome by analyzing plasma viral RNA and peripheral blood mononuclear cell proviral DNA for the presence of drug resistance mutations.
In a prospective study, we investigated the level of TDR in 61 patients by comparing the results of a sensitive multiplex-primer-extension approach (termed HIV-SNaPshot) that is capable of screening for 9 common nucleoside reverse-transcriptase inhibitor and nonnucleotide reverse-transcriptase inhibitor mutations with those of a commercial genotyping kit, ViroSeq (Abbott).
Twenty-two patients were found to carry mutations. More patients with TDR were identified by the HIV-SNaPshot assay than by ViroSeq analysis (33% vs 13%; [P=.015). There was no significant difference in the time from initiation of ART to virological suppression between susceptible patients and those carrying low- or high-level resistance mutations (mean +/- standard deviation, 128 +/- 59.1 vs 164.9 +/- 120.4; P=.147). Furthermore, analyses of CD4 cell counts showed no significant difference between these 2 groups 1 year after the initiation of ART (mean, 184 vs 219 cells/microL; P=.267).
We found the prevalence of TDR in recently infected ART-naive patients to be higher than that estimated by ViroSeq genotyping alone. Follow-up of patients after treatment initiation showed a trend toward there being more clinical complications for patients carrying TDR, although a significant effect on treatment outcome could not be demonstrated. Therefore, the clinical relevance of low-abundance resistant quasispecies in early infection is still in question.

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    • "Prevalence in the treatment-naı¨ve patients was assessed for the 16 RPV-associated RAMs listed in the IAS-USA recommendations: K101E/P, E138A/G/ K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C, and M230I/L. For first-generation NNRTIs, the substitutions K103N, Y181C, G190A/S/E were chosen as herald of RAMs for this class [Jakobsen et al., 2010]. Prevalence of any NNRTIs-related RAMs was compared to any RPV-related (and to the main substitutions , K101E and E138K). "
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    • "Clinical studies aiming at validation of these sensitive methodologies show inconsistent results. Some studies failed to show a significant correlation between the presence of minority variants and subsequent virologic failure (Balduin et al., 2009; Jakobsen et al., 2010; Metzner et al., 2011; Peuchant et al., 2008) while others reported an overt correlation (Geretti et al., 2009; Goodman et al., 2011; Halvas et al., 2010; Johnson et al., 2008; Paredes et al., 2010; Simen et al., 2009). A recent systematic analysis of pooled clinical "
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    • "Characteristic Peuchant 15 2008 Simen 14 2009 Balduin 16 2009 Jakobsen 17 2010 Metzner 18 2010 Goodman 19 2011 Paredes 20 2010 Johnson 21 2008 Geretti 22 2009 Metzner 23 2009 "
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Martin R Jakobsen