RESUMO
The vast majority of HIV-1 infections globally are caused by subtype A or C, although little is known about their drug resistance profiles. We found that HAART-experienced patients infected with subtype A had a lower prevalence of K65R and Y181C than those with subtypes B or C, despite similar exposure to antiretroviral agents that select for these mutations. If confirmed, this information may be important in the planning of antiretroviral regimens in patients infected with HIV-1 subtype A.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV-1 , Adulto , Farmacorresistência Viral Múltipla , Feminino , Infecções por HIV/virologia , HIV-1/genética , Humanos , Masculino , Mutação , Estudos RetrospectivosRESUMO
Zidovudine monotherapy is used to reduce perinatal HIV transmission in women with low viral loads. There are few data on the risk of drug resistance in this select cohort of women. We determined the prevalence of newly acquired mutations conferring reduced sensitivity to zidovudine after exposure during pregnancy, and found that the development of mutations was uncommon and was restricted to women treated before 1998 who had higher baseline viral loads than those currently recommended monotherapy.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/transmissão , HIV-1/genética , Complicações Infecciosas na Gravidez/tratamento farmacológico , Zidovudina/uso terapêutico , Estudos de Coortes , Farmacorresistência Viral , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Transcriptase Reversa do HIV/genética , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mutação/genética , Gravidez , Carga ViralRESUMO
High levels of HIV-1 replication occur following perinatal infection and antiretroviral drugs may not fully suppress viral load during the early years of childhood. Adherence to treatment may also be difficult among children. These two factors will contribute to development of drug resistance but limited paediatric data are available. This study has, therefore, evaluated the prevalence of drug resistance among children and assessed the contribution of adherence to failing therapy. Samples from 26 children who had experienced virological failure to antiretroviral therapy were tested for drug resistance using the Visible Genetics TRUGENE trade mark HIV-1 genotyping assay. HIV-1 subtype was determined using a peptide-based EIA and drug adherence determined by physician assessment. Twenty-four children were black African, 23 of whom were infected with a non-B subtype. HIV RNA sequence data was obtained for 21 of the 26 children; at treatment failure resistance mutations were detected in the protease gene of 7 (33%) and the reverse transcriptase gene of 19 (90%). A lower proportion of children had evidence of drug resistance at nadir and no resistance mutations were detected prior to treatment. Genotypic resistance was common in those treated with lamivudine (10/11, 91%), nevirapine (6/8, 75%), and zidovudine (7/11, 64%). The prevalence of mutations was lower among those receiving other nucleoside reverse transcriptase inhibitors and protease inhibitors. In 50% of children, drug adherence was >90%. Antiretroviral drug resistance was common among this group of children failing therapy, the majority of whom were infected with non-B subtypes of HIV-1. As adherence to treatment was low in 50%, this was likely to be an important contributory factor.
Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Adolescente , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/classificação , HIV-1/genética , Humanos , Lactente , Masculino , Cooperação do Paciente , Inibidores da Transcriptase Reversa/uso terapêutico , Falha de TratamentoRESUMO
BACKGROUND: Nephropathy associated with BK virus (BKVAN) has recently emerged as an important cause of allograft failure following renal transplantation. The aim of this study was to evaluate the effectiveness of laboratory markers in the follow-up of patients with BKVAN. METHODS: Serial samples from seven renal transplant recipients with biopsy proven BKVAN were studied. The median follow-up time from diagnosis was 76 weeks. Intervention after the diagnosis of BKVAN included immunosuppression dose reduction, alternative immunosuppressive agents and/or antiviral therapy with cidofovir. Serial urine samples (n = 127) were collected for electron microscopy (EM), decoy cell detection and quantitative urine BK viral load using real-time polymerase chain reaction. Serum BK viral load was also measured serially (n = 72). RESULTS: All patients showed a reduction in serum and urine viral load during the period of follow-up co-incident with the loss of decoy cells and negative urine EM. Urine samples that were negative for decoy cells or polyomavirus by EM had a urine viral load <10(6) copies/ml and a corresponding serum viral load <10(3) copies/ml. In paired serum/urine samples, there was a proportional relationship between serum and urine viral load with each urine viral load approximately 1000-fold higher than the corresponding serum level. Serum and urine viral loads that decreased to <200 and < 10(6) copies/ml, respectively, correlated with histological improvement. CONCLUSION: Negative EM and absence of decoy cells could be used as broad indicators of a response to intervention. However, measurement of BK virus DNA level provided a wider dynamic range and could be a better choice for determining the extent of viral control.