Prevalence of drug resistance and importance of viral load measurement in Honduran HIV-infected patients failing antiretroviral treatment

Department of Microbiology, National Autonomous University of Honduras, Tegucigalpa, Honduras.
HIV Medicine (Impact Factor: 3.99). 09/2009; 11(2):95-103. DOI: 10.1111/j.1468-1293.2009.00747.x
Source: PubMed

ABSTRACT The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals.
We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the ANRS algorithm.
Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR) = 1) vs. immunological failure (OR = 0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR = 0.037; 95% CI 0.0063-0.22)], route of transmission (OR = 42.8; 95% CI 3.73-491), and years on therapy (OR = 1.81; 95% CI 1.11-2.93).
The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.

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Available from: Ivette L de Rivera, Jan 14, 2015
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    • "We have compared the drug resistance profiles in plasma and PBMCs in a cohort of patients with a long ART history from Honduras, a country with limited resources. Our data show a high concordance (88%, 95% CI: 80.3-94.5) between PBMC and plasma drug resistance profiles which is in agreement with the literatures where the median concordance rate was 87% (IQR: 83-97) [4] [12] [13] [22] [23] [28] [29] "
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    ABSTRACT: Antiretroviral therapy (ART) is being administered in developing nations at unprecedented numbers following the World Health Organization's (WHO) development of standardized first-line drug regimens. To ensure continued efficacy of these drug regimens, WHO recommends monitoring virological responses and development of human immunodeficiency virus (HIV) drug resistance (HIVDR) in HIV-infected patients in a prospective cohort. The current study compared dried fluid spot specimens with the reference standard plasma specimens as a practical tool for viral load (VL) and HIVDR genotyping in resource-limited settings. Dried blood spot (DBS), dried plasma spot (DPS), and plasma specimens were collected from 173 -patients receiving ART at 2 hospital sites in Abuja, Nigeria. HIV-1 VL analysis was performed using NucliSENS EasyQ HIV-1 v1.1 RUO test kits. Genotyping of the HIV-1 pol gene was performed using a broadly sensitive in-house assay. Direct comparison of VL levels showed that DBS specimens, and not DPS specimens, gave results comparable to those of plasma specimens (P = .0619 and .0007, respectively); however, both DBS and DPS specimens had excellent correlation with plasma specimens in predicting virological failure (VL, ≥1000 copies/mL) in patients (κ = 0.78 and 0.83, respectively). Of the 18 specimens with a plasma VL ≥1000 copies/mL, HIVDR genotyping rates were 100% in DBS and 38.9% in DPS specimens, and DBS specimens identified 61 of 65 HIVDR mutations (93.8%) identified in plasma specimens. Our results indicate that DBS specimens could be used for surveys to monitor HIVDR prevention failure in resource-limited settings.
    Clinical Infectious Diseases 03/2012; 54(8):1187-95. DOI:10.1093/cid/cis015 · 8.89 Impact Factor
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    • "We have compared the drug resistance profiles in plasma and PBMCs in a cohort of patients with a long ART history from Honduras, a country with limited resources. Our data show a high concordance (88%, 95% CI: 80.3-94.5) between PBMC and plasma drug resistance profiles which is in agreement with the literatures where the median concordance rate was 87% (IQR: 83-97) [4] [12] [13] [22] [23] [28] [29] "
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    ABSTRACT: The World Health Organization currently does not recommend the use of dried blood spot specimens for drug resistance testing in patients undergoing antiretroviral therapy (ART). Therefore, HIV-1 resistance testing using peripheral blood mononuclear cells (PBMCs) may be of value in resource-limited settings. We compared genotypic resistance profiles in plasma and PBMCs from patients failing ART in two cities of Honduras (Tegucigalpa and San Pedro Sula), a resource-limited country. One hundred patients failing ART were randomly selected from a longitudinal patient monitoring cohort. Plasma and PBMC samples without patient identifier were used for genotypic resistance testing. Sequence data were analyzed, resistance profiles were determined and compared using Stanford HIV Drug Resistance Database algorithm. Specimens with concordant resistance profiles between the two compartments were 88% (95% CI: 80.3% - 94.5 %). Nine specimens (12%, 95% CI: 6.5% - 21.3%) had discordant resistance profiles of clinical significance. Logistic regression analyses indicated that patients on triple therapy were 17.24 times more likely to have concordant drug resistance profile than those on non-triple therapies (OR=17.24, 95% CI: 3.48, 83.33), while patients with increasing number of regimens and years on ART have a decreased rate of concordance (OR = 0.59, 95% CI: 0.32, 1.09 and OR = 0.62, 95% CI: 0.43, 0.88), respectively, than those with less number of regimens and years on ART. Our results show high level of concordance between plasma and PBMC resistance profiles, indicating the possibility of using PBMCs for drug resistance testing in resources-limited settings.
    International Journal of Molecular Epidemiology and Genetics 01/2012; 3(1):56-65. · 1.30 Impact Factor
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    AIDS (London, England) 05/2010; 24(11):1679-87. DOI:10.1097/QAD.0b013e32833a097b · 5.55 Impact Factor
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