Evaluation of viral resistance to Reverse Transcriptase Inhibitors (RTI) in HIV-1-infected patients before and after 6 months of single or double antiretroviral therapy

Abstract

We evaluated samples of peripheral blood mononuclear (PBMC) cells from 46 AIDS patients, before starting therapy with HIV-1 reverse transcriptase inhibitors (RTI), and after 6 months of drug use. PBMC were stored and tested by a Line Probe Assay (LiPA), in order to assess the frequency of RT mutations in this population. Six patients were taking AZT before initial blood collection (1 to 16 weeks of drug use) and 40 patients had no prior therapy. After baseline evaluation, 19 patients received AZT, 23 AZT plus DDI, 3 started AZT only with DDI added after 3 months, and 3 received a combination of AZT plus 3TC. Detection of at least one mutation was found in 33% (15/46) of patients at baseline, and 83% (38/46) had at least 1 mutation after 6 months of therapy. In the majority of cases, samples presented with the wild type and variants of HIV, simultaneously. Patients receiving monotherapy had a higher frequency of mutations (L41 and F214, Y215) than did patients receiving double-drug therapy (19 vs. 10). No specific mutation associated with DDI was identified in 26 patients so treated. Despite the finding of a mean increase in CD4 count and a mild decrease in viral load, patients tended to have an inverse correlation between the CD4 variation and number of mutations detected after 6 months, suggesting potential loss of drug efficacy in the presence of these genotypic changes.

Evaluation of the genotypic pattern of HIV-1 resistance in AIDS patients failing antiretroviral therapy

“…In Brazil, there is little data on HIV-1 drug resistance [20][21][22][23][24]. It is important to evaluate the prevalence rate and mutation pattern for drugs in both naive and treated patients, in order to design better strategies that make www.bjid.com.br better management of antiretroviral therapy possible.…”

Assessing HIV resistance in developing countries: Brazil as a case study

“…The majority of studies that evaluate resistance in the treatment-naive before widespread availability of potent antiretroviral drugs in Brazil (that is, prior to 1997) report a low prevalence of re-sistance to all drug classes (43). 5,6 A single study (44) reported a relatively high prevalence (33%) of resistance to nucleoside reverse transcriptase inhibitors among antiretroviral-naive patients prior to the widespread introduction of ART; the significance of this finding is unclear. More recent studies suggest that transmitted resistance has increased in Brazil since ART became widely available, according to published research (39,(45)(46)(47)(48) and unpublished studies.…”

Virologic therapy response significantly correlates with the number of active drugs as evaluated using a LiPA HIV-1 resistance scoring system

“…Several studies using retrospective data have reported on the ability of the LiPA RT strip assay to predict treatment failure (Brites et al, 2001;Setti et al, 2001;Van Vaerenbergh et al, 2000) and to estimate the prevalence of RT mutations in a population of treatment failures (Tanuri et al, 2002). Although the LiPA Assay does not have the flexibility of the sequence-based systems, it does include most of the key mutations with a few notable exceptions such as K65R a mutation which was quite rare at the time of sampling, which was before the use of tenofovir.…”