Estimating Trends in the Proportion of Transmitted and Acquired HIV Drug Resistance in a Long Term Observational Cohort in Germany

Abstract

ObjectiveWe assessed trends in the proportion of transmitted (TDR) and acquired (ADR) HIV drug resistance and associated mutations between 2001 and 2011 in the German ClinSurv-HIV Drug Resistance Study.MethodThe German ClinSurv-HIV Drug Resistance Study is a subset of the German ClinSurv-HIV Cohort. For the ClinSurv-HIV Drug Resistance Study all available sequences isolated from patients in five study centres of the long term observational ClinSurv-HIV Cohort were included. TDR was estimated using the first viral sequence of antiretroviral treatment (ART) naïve patients. One HIV sequence/patient/year of ART experienced patients was considered to estimate the proportion of ADR. Trends in the proportion of HIV drug resistance were calculated by logistic regression.Results9,528 patients were included into the analysis. HIV-sequences of antiretroviral naïve and treatment experienced patients were available from 34% (3,267/9,528) of patients. The proportion of TDR over time was stable at 10.4% (95% CI 9.1–11.8; p for trend = 0.6; 2001–2011). The proportion of ADR among all treated patients was 16%, whereas it was high among those with available HIV genotypic resistance test (64%; 1,310/2,049 sequences; 95% CI 62–66) but declined significantly over time (OR 0.8; 95% CI 0.77–0.83; p for trend<0.001; 2001–2011). Viral load monitoring subsequent to resistance testing was performed in the majority of treated patients (96%) and most of them (67%) were treated successfully.ConclusionsThe proportion of TDR was stable in this study population. ADR declined significantly over time. This decline might have been influenced by broader resistance testing, resistance test guided therapy and the availability of more therapeutic options and not by a decline in the proportion of TDR within the study population.

A cross-sectional study to characterize local HIV-1 dynamics in Washington, DC using next-generation sequencing

“…An overall DRM prevalence of 1.4%, 35.7%, and 15.7% was estimated for PR, RT, and int, respectively. The [40][41][42][43][44][45][46][47][48][49] year-olds in our study had the highest prevalence of DRMs (22.9%), while the [20][21][22][23][24][25][26][27][28][29] year-olds in our study did not show any DRMs. Overall, DRMs caused amino acid changes in only one codon position in PR, while 22 and 9 different codons positions changed in RT and int, respectively, when analyzing the consensus sequences.…”

“…In treatment-naïve participants, both when using consensus sequences and haplotypes, we estimated a low prevalence rate of DRMs (14.3%). Similarly, low prevalence rates have been seen in the past in the US ( 42 ; 15% between 1999 and 2011) and even lower in treatment-naïve individuals in Europe ( 41,(43)(44)(45) ; 10% between 2001 and 2013). Moreover, we also found fewer DRMs in treatment-naïve participants compared to a recent study of PLWH in DC 28 (22.5% between 1994 and 2013).…”

“…The only codon position predicted by FUBAR in the haplotypes was 230 for int, and it is associated with reduced susceptibility to integrase inhibitors (INSTI) 27 . Seven (4,34,41,43,44,45,64) and eight (22,40,84,92,93,95,105,111) codons were inferred to be under positive selection for V1V2 and V3 haplotype sequences, respectively. Interestingly, only a handful of inferred positively selected codons overlapped between the haplotype and consensus sequences, those were at position 35 for RT; positions 201, 265, and 283 for int; 34 for V1V2; and 93 for V3.…”

Transmission of HIV drug resistance

“…TDR rates -as determined by conventional sequencing -have for several years now remained stable at around 9-11% in Europe [6,7,9]. Whereas techniques are becoming more robust, sensitive assays will need to be studied carefully in different populations to determine clinical utility before they can be applied routinely to guide practice.…”

Triple Class HIV-1 Drug Resistance in Croatia: the First Report

“…The prevalence of TDR in treatment-naive individuals remains stable in most developed countries and the prevalence of acquired drug resistance is decreasing [22][23][24][25][26][27][28][29] . This implies that further transmission of HIV-1 with TDRMs is occurring in ART-naive individuals [6][7][8] .…”