Community Resistance and Transmitted HIV Drug Resistance
Objectives. As community viral load (CVL) measurements are associated with the incidence of new HIV-1 infections in a population, we hypothesized that similarly measured community drug resistance (CDR) could predict the prevalence of transmitted drug resistance (TDR).
Methods. Between 2001 and 2011, the prevalences of HIV-1 drug resistance for patients with established infection receiving HIV care (i.e. CDR) and TDR in recently infected patients were determined in San Diego. At each position in HIV-1 reverse transcriptase (RT) and protease (pro), drug resistance was evaluated both as the overall prevalence of resistance-associated mutations and by weighting each resistance position to the concurrent viral load of the patient and its proportion to the total viral load of the clinic (CVL). The weighting was the proportion of the CVL associated with patients identified with resistance at each residue. Spearman ranked correlation coefficients were used to determine associations between CDR and TDR.
Results. We analysed 1088 resistance tests for 971 clinic patients and baseline resistance tests for 542 recently infected patients. CDR at positions 30, 46, and 88 in pro was associated with TDR between 2001 and 2011. When CDR was weighted by the viral load of patients, CDR was associated with TDR at position 103 in RT. Each of these associations was corroborated at least once using shorter measurement intervals.
Conclusions. Despite evaluation of a limited percentage of chronically infected patients in San Diego, CDR correlated with TDR at key resistance positions and therefore may be a useful tool with which to predict the prevalence of TDR.
Mutations in the HIV-1 pol gene can confer decreased susceptibility to antiretroviral therapy (ART). Failure of ART to fully suppress viral replication (i.e. treatment failure) can select for viral populations that harbour these mutations in the presence of ongoing therapy. These mutations can also be found in viral populations among people who have never taken ART, representing transmitted drug resistance (TDR). The primary source of TDR is from patients on failing ART regimens with incomplete viral suppression in whom drug resistance mutations have been selected or from subjects with TDR. As measures of HIV-1 viral load at the community level [i.e. community viral load (CVL)] have recently been shown to be associated with the incidence of new HIV infections in general populations as well as specific high-risk groups, we speculated that similar measures of community drug resistance (CDR) could be related to the prevalence of overall TDR. Specifically, we tested the hypothesis that CDR, calculated for a limited group of patients receiving care at a local HIV clinic with sufficient viral loads and resistance data available, could be associated with the prevalence of TDR in people recently infected with HIV in the same community over the same time period.
Abstract and Introduction
Abstract
Objectives. As community viral load (CVL) measurements are associated with the incidence of new HIV-1 infections in a population, we hypothesized that similarly measured community drug resistance (CDR) could predict the prevalence of transmitted drug resistance (TDR).
Methods. Between 2001 and 2011, the prevalences of HIV-1 drug resistance for patients with established infection receiving HIV care (i.e. CDR) and TDR in recently infected patients were determined in San Diego. At each position in HIV-1 reverse transcriptase (RT) and protease (pro), drug resistance was evaluated both as the overall prevalence of resistance-associated mutations and by weighting each resistance position to the concurrent viral load of the patient and its proportion to the total viral load of the clinic (CVL). The weighting was the proportion of the CVL associated with patients identified with resistance at each residue. Spearman ranked correlation coefficients were used to determine associations between CDR and TDR.
Results. We analysed 1088 resistance tests for 971 clinic patients and baseline resistance tests for 542 recently infected patients. CDR at positions 30, 46, and 88 in pro was associated with TDR between 2001 and 2011. When CDR was weighted by the viral load of patients, CDR was associated with TDR at position 103 in RT. Each of these associations was corroborated at least once using shorter measurement intervals.
Conclusions. Despite evaluation of a limited percentage of chronically infected patients in San Diego, CDR correlated with TDR at key resistance positions and therefore may be a useful tool with which to predict the prevalence of TDR.
Introduction
Mutations in the HIV-1 pol gene can confer decreased susceptibility to antiretroviral therapy (ART). Failure of ART to fully suppress viral replication (i.e. treatment failure) can select for viral populations that harbour these mutations in the presence of ongoing therapy. These mutations can also be found in viral populations among people who have never taken ART, representing transmitted drug resistance (TDR). The primary source of TDR is from patients on failing ART regimens with incomplete viral suppression in whom drug resistance mutations have been selected or from subjects with TDR. As measures of HIV-1 viral load at the community level [i.e. community viral load (CVL)] have recently been shown to be associated with the incidence of new HIV infections in general populations as well as specific high-risk groups, we speculated that similar measures of community drug resistance (CDR) could be related to the prevalence of overall TDR. Specifically, we tested the hypothesis that CDR, calculated for a limited group of patients receiving care at a local HIV clinic with sufficient viral loads and resistance data available, could be associated with the prevalence of TDR in people recently infected with HIV in the same community over the same time period.
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