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HIV Med ; 11(8): 483-92, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20163482

ABSTRACT

OBJECTIVES: Transmitted HIV strains may harbour drug resistance mutations. HIV-1 drug resistance mutations are currently detected in plasma viral RNA. HIV-1 proviral DNA could be an alternative marker, as it persists in infected cells. METHODS: This was a prospective study assessing the prevalence and persistence of HIV-1 drug resistance mutations in DNA from CD4 cells before and after protease inhibitor (PI)- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy initiation in 69 drug-naïve patients. RESULTS: Before therapy, 90 and 66% of detected mutations were present in CD4 cells and plasma, respectively. We detected seven key mutations, and four of these (M184M/V, M184M/I, K103K/N and M46M/I) were only found in the cells. When treatment was started, 40 patients were followed; the mutations detected at the naïve stage remained present for at least 1 year. Under successful treatment, new key mutations emerged in CD4 cells (M184I, M184M/I and Y188Y/H). CONCLUSIONS: The proportion of mutations detected in the DNA was statistically significantly higher than that detected in standard RNA genotyping, and these mutations persisted for at least 1 year irrespective of therapy. The pre-existence of resistance mutations did not jeopardise treatment outcome when the drug concerned was not included in the regimen. Analysis of HIV-1 DNA could be useful in chronic infections or when switching therapy in patients with undetectable viraemia.


Subject(s)
DNA, Viral/analysis , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV-1/genetics , Proviruses/genetics , RNA, Viral/analysis , Adult , Aged , Amino Acid Sequence , Anti-Retroviral Agents/therapeutic use , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/virology , DNA Mutational Analysis , DNA, Viral/genetics , Drug Therapy, Combination , Female , Genotype , HIV Infections/blood , HIV Infections/drug therapy , HIV-1/drug effects , HIV-1/isolation & purification , Humans , Logistic Models , Male , Middle Aged , Mutation/drug effects , Mutation/genetics , Prevalence , Prospective Studies , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , Statistics, Nonparametric , Viral Load , Young Adult
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