RESUMEN
OBJECTIVE: Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. DESIGN: A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. METHODS: Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (<1996) were compared with those treated later (1996-2008). RESULTS: Anal cancer cases (nâ=â37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70âcells/µl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, Pâ=â0.002], with a CD4 cell count nadir less than 100âcells/µl (AHR 2.21, 95% CI 1.06-4.62, Pâ=â0.035) and longer duration of CD4 cell count less than 100âcells/µl (AHR 1.33, 95% CI 1.11-1.58, Pâ=â0.002). CONCLUSION: Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.
Asunto(s)
Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Neoplasias del Ano/prevención & control , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina , Adulto , Neoplasias del Ano/inmunología , Estudios de Cohortes , Susceptibilidad a Enfermedades , Infecciones por VIH/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de TiempoRESUMEN
In 2002, the British Columbia (BC) Centre for Excellence in HIV/AIDS collected final detailed data on complementary and alternative medicine (CAM) use in their HIV treatment program. This cross-sectional study of 682 participants examines types and determinants of CAM use in this program, and examines adverse effects associated with CAM use and antiretroviral therapy (ART). Among the 47% ever CAM users in the included population, vitamins/minerals (81%), meditation/yoga (36%), massage (31%), marijuana (30%), dietary supplements (24%), and herbal medicines (19%), were most commonly used. Multivariate analysis indicated CAM users were less likely to have low education (AOR=0.51), more likely to be unemployed (AOR=1.52), more likely to have been on ART longer (AOR=1.19), and more likely to experience objective, action-requiring (OA) side effects (AOR=1.45). CAM use is common. Both patients and health professionals should be aware of potential toxicities and drug interactions related to the use of CAM and HIV/AIDS treatment.
Asunto(s)
Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Terapias Complementarias/estadística & datos numéricos , Infecciones por VIH/terapia , Conocimientos, Actitudes y Práctica en Salud , Adulto , Colombia Británica/epidemiología , Estudios de Cohortes , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Interacciones de Hierba-Droga , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Educación del Paciente como Asunto/organización & administración , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
BACKGROUND: The prevalence of antiretroviral resistance among persons enrolled in the centralized HIV/AIDS Drug Treatment Program in British Columbia, Canada, who had died between July 1997 and December 2001, was investigated, to determine the degree to which antiretroviral resistance contributed to mortality. METHODS: During this period, 637 deaths had occurred. The last plasma sample obtained during therapy was genotyped retrospectively for treated individuals who had died of a nonaccidental cause. Samples with plasma human immunodeficiency virus (HIV) loads <500 copies/mL were not genotyped. Drug resistance among 1220 living HIV-infected persons who had experienced virologic therapy failure during the study period also was examined. RESULTS: Of 554 individuals who had died of nonaccidental causes, 58 (10.4%) were antiretroviral naive, and 99 (17.9%) had very brief exposure to antiretroviral therapy (median, 2 months). The majority of isolates from the remaining 397 individuals harbored either no major resistance mutations or represented samples with plasma HIV suppression of <500 copies/mL. Resistance to >/=1, >/=2, or 3 drug classes was observed in 76%, 42%, and 11% of individuals, respectively, in the group of 1220 living individuals experiencing virologic therapy failure, compared with only 44%, 23%, and 5% of individuals, respectively, who had died (P<.001). CONCLUSION: Only a relatively low prevalence of multidrug resistance was observed in this cohort, indicating that the exhaustion of treatment options because of drug resistance was not a significant contributor to mortality.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH/efectos de los fármacos , Adulto , Sustitución de Aminoácidos , Fármacos Anti-VIH/farmacología , Colombia Británica , Farmacorresistencia Viral Múltiple/genética , Femenino , Genotipo , VIH/genética , VIH/aislamiento & purificación , Infecciones por VIH/mortalidad , Proteasa del VIH/genética , Inhibidores de la Proteasa del VIH/farmacología , Inhibidores de la Proteasa del VIH/uso terapéutico , Transcriptasa Inversa del VIH/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Prevalencia , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga ViralRESUMEN
We assessed the prevalence and clinical impact of insertions within the HIV-1 p6Gag proline-rich (PTAP) region on initial antiretroviral therapy response in 461 HIV-infected, drug-naive individuals initiating therapy in British Columbia, Canada between June 1996 and August 1998. HIV p6Gag insertions were detected by nested RT-PCR of extracted patient plasma followed by direct DNA sequencing. Insertions were observed in 70 of 423 successfully genotyped samples (16.5%). HIV p6Gag insertions were significantly associated with a lower baseline CD4 cell count (P<<0.05) and the presence of basic amino acids at key positions in the HIV envelope V3 loop linked to a syncytium-inducing phenotype (P<<0.05). After adjusting for baseline factors, no effect of HIV p6Gag insertions was observed on time to virological success (pVL < or = 500 copies/ml), virological failure (subsequent confirmed pVL > or = 500 copies/ml) or immunological failure (confirmed CD4 count below baseline), as evaluated by Kaplan-Meier methods and Cox proportional hazard regression (P>0.1). The data suggest that HIV p6Gag insertions are not exclusively related to drug resistance and may not influence response to antiretroviral therapy, but may be linked to sequence variations in the HIV envelope.
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Fármacos Anti-VIH/uso terapéutico , Productos del Gen gag/genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Adulto , Colombia Británica , Recuento de Linfocito CD4 , Estudios de Cohortes , Farmacorresistencia Viral/genética , Femenino , Genotipo , Proteína gp120 de Envoltorio del VIH/genética , Infecciones por VIH/epidemiología , Infecciones por VIH/patología , VIH-1/efectos de los fármacos , VIH-1/aislamiento & purificación , Humanos , Masculino , Mutagénesis Insercional/genética , Fragmentos de Péptidos/genética , Prevalencia , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Carga Viral , Productos del Gen gag del Virus de la Inmunodeficiencia HumanaRESUMEN
OBJECTIVE: Single nucleotide polymorphisms (SNP) in the genes encoding the human CX3CR1 chemokine receptor and the P-glycoprotein multidrug transporter have been associated with accelerated disease progression in untreated individuals and implicated in therapeutic response, respectively. This retrospective study assessed the influence of SNP in the CX3CR1 and MDR-1 genes on initial virological and immunological response in 461 HIV-infected, antiretroviral-naive individuals initiating antiretroviral therapy in British Columbia, Canada. METHODS: CX3CR1 and MDR-1 SNP were determined by PCR amplification of human DNA from plasma, followed by DNA sequencing. Time to virological success [time to HIV plasma viral load (pVL) < or = 500 copies/ml], virological failure (subsequent time to the second of two consecutive pVL > or = 500) and immunological failure (time to the second consecutive CD4 cell count below baseline) were analyzed by Kaplan-Meier methods. RESULTS: Frequencies of CX3CR1 amino acid haplotypes were 249V 280T (0.75), 249I 280M (0.15), and 249I 280T (0.1). Frequencies of MDR-1 nucleotide polymorphisms were 3435C (0.47) and 3435T (0.53). There was no effect detected for SNP in CX3CR1 or MDR-1 on time to virological success, nor of CX3CR1 and MDR-1 SNP on time to virological and immunological failure, respectively ( P > 0.1). There was a trend to earlier virological failure in the MDR-1 3435C/C genotype group ( P = 0.07), and a statistically significant trend to earlier immunological failure in individuals with the CX3CR1 249I polymorphism ( P = 0.02). These remained significant after correcting for baseline age, sex, pVL, CD4 cell count, type of therapy, and adherence ( P < or = 0.05). CONCLUSION: Polymorphisms in MDR-1 and CX3CR1 may be associated with accelerated virological and immunological therapy failure, respectively.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Genes MDR/genética , Infecciones por VIH/genética , Proteínas de la Membrana , Polimorfismo de Nucleótido Simple , Receptores de Quimiocina/genética , Adulto , Recuento de Linfocito CD4 , Receptor 1 de Quimiocinas CX3C , Femenino , Frecuencia de los Genes , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/fisiología , Haplotipos , Humanos , Masculino , Análisis Multivariante , Estudios Retrospectivos , Insuficiencia del Tratamiento , Carga ViralRESUMEN
OBJECTIVE: To provide population-based incidence estimates for constituent symptoms of human immundeficiency virus (HIV)-related lipodystrophy syndrome and to identify possible independent predictors of accrued cases. DESIGN: Prospective population-based cohort. Methods Study subjects were antiretroviral-naïve individuals who initiated treatment between October 1998 and May 2001 and provided completed self-reported data regarding the occurrence of lipoatrophy, lipohypertrophy and increased triglyceride and cholesterol levels. Possible predictors of incident lipoatrophy, lipohypertrophy, dyslipidaemia and mixed lipodystrophy (symptoms of both lipoatrophy and lipohypertrophy) were identified using logistic regression modelling. A sub-analysis restricted to subjects retaining original treatment at study completion was conducted using similar methods. RESULTS: Among the 366 study subjects, cumulative incidence was 29% for lipoatrophy, 23% for lipohypertrophy, 9% for dyslipidaemia, and 13% for mixed lipodystrophy after a median duration of 12 months of antiretroviral therapy. In an intentto-treat analysis incident lipoatrophy and lipohypertrophy were independently associated with initiation of protease inhibitor (PI)-containing regimens, (adjusted odds ratio [AOR] = 1.94; 95% CI: 1.25-3.03 and AOR = 1.76; 95% CI: 1.09-2.85, respectively) and female gender (AOR = 2.06; 95% CI: 1.03-4.12 and AOR = 2.36; 95% CI: 1.17-4.74, respectively). Both mixed lipodystrophy and reported dyslipidaemia were associated only with PI inclusion in the initial regimen (AOR = 2.27; 95% CI: 1.14-4.53 and AOR = 2.14; 95% CI: 1.26-3.65, respectively). Similar results were obtained in analysis of individuals retained in initial treatment groups throughout follow-up. CONCLUSION: Incident morphological and lipid abnormalities are common among individuals initiating first-time antiretroviral therapy. Use of PI was consistently associated with all lipodystrophy-related abnormalities after adjustment for a broad range of patient personal, clinical and treatment characteristics.
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Terapia Antirretroviral Altamente Activa/efectos adversos , Inhibidores de la Proteasa del VIH/efectos adversos , Síndrome de Lipodistrofia Asociada a VIH/epidemiología , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Colesterol/sangre , Femenino , Inhibidores de la Proteasa del VIH/uso terapéutico , Síndrome de Lipodistrofia Asociada a VIH/sangre , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Humanos , Incidencia , Modelos Logísticos , Masculino , Estudios Prospectivos , Sexo , Triglicéridos/sangreRESUMEN
INTRODUCTION: Co-infection with GBV-C ('Hepatitis G' virus) appears to be associated with slower disease progression in HIV-infected, untreated individuals. We wished to determine whether detection of GBV-C RNA was associated with differential response to HIV therapy in a population-based cohort of 461 individuals initiating antiretroviral therapy between June 1996 and August 1998, in British Columbia, Canada. METHODS: The presence of GBV-C RNA in plasma was identified by nested RT-PCR, using detection of HIV RNA as a positive control. Time to virological success [achieving HIV plasma viral load (pVL) < or = 500 copies/ml], virological failure (subsequent confirmed pVL > 500 copies/ml) and immunological failure (confirmed CD4 cell count below baseline) were assessed by Kaplan-Meier methods and Cox proportional hazard regression. RESULTS: Of the 441 individuals for whom results were available, 90 (20.4%) had detectable plasma GBV-C RNA. GBV-C RNA was significantly associated with a lower HIV pVL at baseline (P = 0.004). In univariate and multivariate Cox models, GBV-C RNA positive and negative individuals did not differ with respect to time to virological success [risk ratio (RR), 0.98; 95% confidence interval (CI), 0.75-1.27], time to virological failure (RR, 1.10; 95% CI, 0.74-1.65), or time to immunological failure (RR, 1.09; 95% CI, 0.73-1.63). There was no correlation between detection of GBV-C RNA and mutations in the human chemokine receptors CCR5 and CX CR1, or HIV viral tropism as predicted by the HIV envelope sequence (P > 0.1). CONCLUSION: GBV-C viremia is relatively common in individuals seeking treatment for HIV infection; however, it does not appear to have any effect on initial antiretroviral therapy response.
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Infecciones por Flaviviridae/complicaciones , Virus GB-C , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Hepatitis Viral Humana/complicaciones , Viremia/complicaciones , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Infecciones por Flaviviridae/virología , VIH/crecimiento & desarrollo , VIH/aislamiento & purificación , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Humanos , Masculino , Plasma , Modelos de Riesgos Proporcionales , ARN Viral/sangre , ARN Viral/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Carga Viral , Viremia/virologíaRESUMEN
This study provides population-based estimates of the incidence of constituent symptoms associated with HIV-related lipodystrophy syndrome. Possible predictors of symptomatology based on analysis of accrued cases are provided after adjustment for a broad range of personal, clinical, and treatment characteristics. Patients enrolled in a province-wide HIV/AIDS treatment program reported annually on the occurrence of lipoatrophy, lipohypertrophy, and elevated triglyceride and cholesterol levels. Of 1261 individuals who provided baseline data, 745 were available at follow-up, among whom incidence was 27% for lipoatrophy, 21% for lipohypertrophy, and 10% and 16% for increased triglyceride and cholesterol levels, respectively. In logistic multivariate modeling, incident lipoatrophy was associated with duration of stavudine (per quarter) (adjusted odds ratio [AOR] 1.18; 95% confidence interval [CI] 1.09-1.27) and having been diagnosed with AIDS (AOR 2.07; 95% CI 1.20-3.56). Lipohypertrophy risk increased with use of protease inhibitor (AOR 3.53; 95% CI 1.81-6.86) and stavudine (AOR 3.67; 95% CI 1.61-8.38). Incident cholesterol or triglyceride abnormalities were associated with protease inhibitor use (AOR 7.17; 95% CI 2.46-20.96) and duration of ritonavir (per quarter) (AOR 1.12; 95% CI 1.04-1.21). Our findings suggest high annual rates of incidence and a role of first line antiretroviral therapies in symptom development. These outcomes, in conjunction with the findings of others have important implications for evolving treatment patterns.