Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen

Fernandes Hospital, Infectious Diseases Unit, Buenos Aires, Argentina.
Antiviral therapy (Impact Factor: 3.02). 01/2008; 13(1):135-9.
Source: PubMed


Emergence of nevirapine (NVP) resistance may be a consequence of its use in monotherapy to prevent HIV mother-to-child transmission (MTCT). The aim of this study was to evaluate the emergence of strains resistant to NVP and lamivudine (3TC) after discontinuation of antiretroviral therapy (ART) with 3TC/zidovudine (ZDV)/NVP.
Twenty pregnant women (ART-naive or preexposed only to ZDV), to whom 3TC/ZDV/NVP was prescribed as MTCT prophylaxis, were studied. They received ART for a median of 4 months with median viral load (VL) at labour <50 copies/ml. Samples were collected between 1 and 15 months (median: 3 months) after ART interruption. Sequence-selective real-time PCR (SPCR), which quantifies minority viral populations containing K103N, Y181C and M184V mutations, and standard genotypic sequencing were assayed.
No mutations associated with resistance to 3TC or NVP were found by standard population sequencing. Analysis of K103N by SPCR showed that 35% of the patients contained < or =0.1% of viruses carrying either the AAC or AAT mutations. For Y181C mutation, 10% of the patients contained <0.5% of viruses with TGT codon change. For M184V mutation, one patient contained 6.2% of virus with GTG mutation and 13 patients (65%) contained <0.9% of mutated viruses. Four women were re-exposed to 3TC/ZDV/NVP and achieved HIV VL <50 copies/ml. No perinatal transmission occurred in any of the 22 births.
NVP associated with ZDV/3TC as a regimen to prevent MTCT may involve a low risk for the selection of antiretroviral-resistant strains and may not jeopardize the use of these same drugs for future treatment.

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Available from: Moira Vignoles, Apr 10, 2014
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    ABSTRACT: The aim of this study was to describe the frequency of minority populations of viruses carrying mutations K103N and M184V in drug-naive HIV type-1 (HIV-1)-infected children, and to further evaluate their effect on the selection of drug-resistant viruses within highly active antiretroviral therapy (HAART). Newly diagnosed vertically HIV-1-infected children were evaluated. The HIV-1 pol gene was sequenced for subtyping and antiretroviral drug resistance analysis. Standard genotypic sequencing and sequence-selective real-time PCR (SPCR) to quantify minority viral populations were used. From December 2004 to July 2006, we included 35 children who were studied at baseline and during their first HAART regimen (follow-up median time 29.4 months). Of them, 82.9% were infected with intersubtype B/F recombinant variants. At baseline, all children had a drug-susceptible viral population that was studied by bulk sequencing. SPCR showed that 4 children had between 2-10% of M184V, 11 had <0.7%, 18 had no detectable mutation and 2 could not be amplified. No K103N minority populations were found. Once under HAART, children who had 2-10% of M184V at baseline further selected it in percentages >20% in less time than those with -0.1-0.6% or without minority populations (P=0.01). It was shown that having 2-10% of M184V at baseline enhanced its selection in high percentages in a short time after HAART initiation. Further research regarding the presence of minority quasispecies before initiation of HAART in large paediatric populations should be undertaken to evaluate their clinical effect during HAART.
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