RESUMEN
Background: Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. Methods: The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. Results: The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000â copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200â copies/mL. Conclusion: In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50â copies/mL.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral Múltiple , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Carga Viral , Adulto , Terapia Antirretroviral Altamente Activa , Femenino , Francia , Genes Virales , Genotipo , Infecciones por VIH/sangre , Integrasa de VIH/sangre , Integrasa de VIH/genética , Proteasa del VIH/sangre , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/sangre , Transcriptasa Inversa del VIH/genética , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Análisis de Secuencia de ADN , Insuficiencia del TratamientoRESUMEN
There is evidence that HIV-1 evolution under maraviroc (MVC) pressure can lead to the selection of either X4-tropic variants and/or R5-tropic, MVC-resistant isolates. However, the viral dynamics of HIV-1 variants in patients with virological failure (VF) on MVC-containing regimens remain poorly studied. Here, we investigated the V3 loop evolution of HIV-1 on MVC in relation to coreceptor usage and the nature of HIV-1 quasispecies before MVC therapy using bulk population sequences and ultradeep sequencing. The majority of patients had no detectable minority X4 variant at baseline. The evolution of tropism was followed up until VF and showed three possibilities for viral evolution in these patients: emergence of preexisting X4 variants, de novo selection of R5 variants presenting V3 loop mutations, or replication of R5 variants without selection of known mutations.
Asunto(s)
Ciclohexanos/uso terapéutico , Proteína gp120 de Envoltorio del VIH/genética , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Fragmentos de Péptidos/genética , Receptores CCR5/genética , Receptores CXCR4/genética , Triazoles/uso terapéutico , Antagonistas de los Receptores CCR5 , Farmacorresistencia Viral , Evolución Molecular , Genotipo , VIH-1/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Maraviroc , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Selección Genética , Análisis de Secuencia de ARN , Tropismo ViralRESUMEN
BACKGROUND: The K65R HIV-1 reverse transcriptase (RT) mutation is a multidrug resistance mutation which may be correlated with specific antiretroviral combinations and with the presence or absence of other RT resistance mutations. OBJECTIVES: The aims of this study were: (i) to determine the prevalence of the K65R mutation in a cohort of antiretroviral-treated patients; (ii) to study genotypic patterns and treatment characteristics in patients in whom the K65R mutation was present. STUDY DESIGN: We included in the study all antiretroviral-experienced patients followed up at the Bordeaux University Hospital in 2003 and 2004 for whom an HIV-1 genotypic resistance analysis was available. Information on RT resistance mutations was reported from a hospital database including therapeutic and biological parameters. The prevalence of K65R was investigated for all patients. Genotypic patterns and treatment characteristics were examined at the time of detection of the K65R mutation. RESULTS: The prevalence of K65R was 1.9% (26 of 1404 patients). K65R was associated with nucleoside RT inhibitor-based regimens in 22 patients, and with tenofovir disoproxil fumarate, lamivudine, didanosine and abacavir in 23, 17, 17 and eight patients, respectively. The M184V and Q151M mutations were the most commonly co-selected substitutions. Thymidine analogue mutations (TAMs) were rarely co-selected with K65R and inversely associated with K65R. CONCLUSION: The K65R mutation may emerge preferentially in the absence of zidovudine and TAMs, suggesting the possibility of an antagonistic interaction between K65 and TAMs.