Non-nuke HIV strains resistant to ARVs

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People contracting HIV increasingly acquire strains that are resistant to antiretrovirals (ARVs), in particular non-nucleoside reverse transcriptase inhibitors (NNRTIs, or non-nukes). Researchers analysed data on 496 HIV-positive participants in the San Diego Primary Infection Cohort, looking at 1996 to 2013. The members of the group studied all underwent genotypic resistance testing before starting ARVs.

Overall, 13.5% (67 of 496) of the cohort had transmitted drug resistance (TDR). Over time, the rate of TDR increased. The predominant TDR was among non-nukes, at 8.5% (42 of 496) of the cohort; this rate also saw an upward trend. The rate of TDR to protease inhibitors and nucleoside/nucleotide reverse transcriptase inhibitors was a respective 4.4% (22 of 496) and 3.8% (19 of 496); these rates remained constant over time.

The prevalence of TDR did not differ by individuals’ age, sex, race or ethnicity, or their risk factors in contracting HIV.

The researchers concluded, “These findings highlight the importance of baseline resistance testing to guide selection of (HIV treatment) and for public health monitoring.”

Abstract
Background: Transmitted drug resistance (TDR) remains an important concern when initiating antiretroviral therapy (ART). Here, we describe the prevalence and phylogenetic relationships of TDR among ART-naive, HIV-infected individuals in San Diego from 1996 to 2013.
Methods: Data were analyzed from 496 participants of the San Diego Primary Infection Cohort who underwent genotypic resistance testing before initiating therapy. Mutations associated with drug resistance were identified according to the WHO-2009 surveillance list. Network and phylogenetic analyses of the HIV-1 pol sequences were used to evaluate the relationships of TDR within the context of the entire cohort.
Results: The overall prevalence of TDR was 13.5% (67/496), with an increasing trend over the study period (P = 0.005). TDR was predominantly toward nonnucleoside reverse transcriptase inhibitors (NNRTIs) [8.5% (42/496)], also increasing over the study period (P = 0.005). By contrast, TDR to protease inhibitors and nucleos(t)ide reverse transcriptase inhibitors were 4.4% (22/496) and 3.8% (19/496), respectively, and did not vary with time. TDR prevalence did not differ by age, gender, race/ethnicity, or risk factors. Using phylogenetic analysis, we identified 52 transmission clusters, including 8 with at least 2 individuals sharing the same mutation, accounting for 23.8% (16/67) of the individuals with TDR.
Conclusions: Between 1996 and 2013, the prevalence of TDR significantly increased among recently infected ART-naive individuals in San Diego. Around one-fourth of TDR occurred within clusters of recently infected individuals. These findings highlight the importance of baseline resistance testing to guide selection of ART and for public health monitoring.

Poz material
Journal of Acquired Immune Deficiency Syndromes abstract


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