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Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda.

Ahoua L, Guenther G, Pinoges L, Anguzu P, Chaix ML, Le Tiec C, Balkan S, Olson D, Olaro C, Pujades-Rodríguez M

HIV/AIDS Department, Epicentre, Paris, France. laurence.ahoua@epicentre.msf.org

BACKGROUND: Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART) treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. METHODS: Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/ml) and subtherapeutic antiretroviral (ARV) concentrations were investigated with multiple logistic regression. RESULTS: At 12 and 24 months of ART, 72% (n = 701) and 70% (n = 369) of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (<400 copies/ml). Risk factors for virological failure (>1,000 copies/ml) were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. CONCLUSION: Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy.

Published 25 June 2009 in BMC Infect Dis, 9: 81.
Full-text of this article is available online (may require subscription).


Articles on Virology published 25 June 2009:

Pegylated interferon alpha-2b (Peg-IFN alpha-2b) affects early virologic response dose-dependently in patients with chronic hepatitis C genotype 1 during treatment with Peg-IFN alpha-2b plus ribavirin.   J Viral Hepat.

Chronic hepatitis C (CH-C) genotype 1 patients who achieved early virologic response have a high probability of sustained virologic response (SVR) following pegylated interferon (Peg-IFN) plus ribavirin therapy. This study was conducted to evaluate how reducing drug doses affects complete early virologic response (c-EVR) defined as hepatitis C virus (HCV) RNA negativity at week 12. Nine hundred eighty-four patients with CH-C genotype 1 were enrolled. Drug doses were evaluated independently on a ... [Abstract] [Full-text]


Articles on Virology published 24 June 2009:

Virological evaluation of domestic water purification devices commonly used in India emphasizes inadequate quality and need for virological standards.   Trop Med Int Health.

Summary Objectives To evaluate the performance of domestic water purification units with respect to contaminating enteric viruses. Methods Eight domestic water purification systems widely used in India were evaluated using hepatitis E virus (HEV) as a model virus. For HEV concentration and detection, membrane filtration and real-time PCR were used respectively. Viral log reduction value (LRV) was calculated for each unit. Results Viral log reduction value was 0.21 for unit 6 (polyester + ... [Abstract] [Full-text]

Association between specific HIV-1 env traits and virologic control in vivo.   Infect Genet Evol.

HIV RNA levels are influenced by genetic characteristics of both the host and the virus. Here we applied machine learning techniques to determine if plasma-derived HIV-1 amino acid sequences can be used to predict spontaneous virologic control. We studied the relationship between HIV-1 env genotype and viral load in 20 chronically infected patients undergoing treatment interruptions (SSITT, Swiss-Spanish Intermittent Treatment Trial) and in 104 primary HIV infected (PHI) patients before ... [Abstract] [Full-text]


Articles on Virology published 23 June 2009:

Virological and Biochemical Features in Elderly HCV Patients with Hepatocellular Carcinoma: Amino Acid Substitutions in HCV Core Region as Predictor of Mortality after First Treatment.   Intervirology, 52(4): 179-188.

Aims: We showed previously that amino acid (aa) substitutions in HCV genotype 1b (HCV-1b) core region are negative predictors of virological response to peginterferon + ribavirin therapy, and also risk factors of hepatocarcinogenesis. The aim of this study was to evaluate the impact of core aa substitutions on mortality in elderly patients. Methods: We compared the characteristics and survival of 92 elderly (>/=75 years) patients with HCV-related hepatocellular carcinoma (HCC) (including 62 ... [Abstract] [Full-text]


Articles on Virology published 22 June 2009:

Virological and immunological stability in HIV infected patients undergoing partial-treatment interruption.   J Clin Virol.

BACKGROUND: Partial-treatment interruption in patients with drug-resistant viremia has been associated with stable HIV RNA levels suggesting that interruption of protease inhibitors may be an effective strategy for patients without other therapeutic options while waiting for the development of new drugs. OBJECTIVE: Our goal was to maintain virological and immunological stability in patients experiencing virologic failure with multiresistant HIV to allow access to newly developed antiretroviral ... [Abstract] [Full-text]


Articles on Virology published 19 June 2009:

Evolution of CD4+ T cell count in HIV-1-infected adults receiving antiretroviral therapy with sustained long-term virological suppression.   AIDS Res Hum Retroviruses, 25(6): 756-76.

It is not fully elucidated whether patients who receive antiretroviral therapy (ART) can maintain continued CD4 count increases. Previous studies suggested a plateau 2-4 years after treatment initiation. We aimed to characterize the evolution of CD4 counts in HIV-infected individuals receiving long-term suppressive ART, by performing a retrospective study of patients who maintained viral suppression (HIV RNA <400 copies/ml) for > or =5 years. We used linear regression models to determine ... [Abstract] [Full-text]


Articles on Virology published 15 June 2009:

A comparison of three computational modelling methods for the prediction of virological response to combination HIV therapy.   Artif Intell Med.

OBJECTIVE: HIV treatment failure is commonly associated with drug resistance and the selection of a new regimen is often guided by genotypic resistance testing. The interpretation of complex genotypic data poses a major challenge. We have developed artificial neural network (ANN) models that predict virological response to therapy from HIV genotype and other clinical information. Here we compare the accuracy of ANN with alternative modelling methodologies, random forests (RF) and support vector ... [Abstract] [Full-text]

Impact of ribavirin plasma level on sustained virological response in patients treated with pegylated interferon and ribavirin for chronic hepatitis C.   Aliment Pharmacol Ther.

Abstract Background. The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). However, the impact of the pharmacological properties of ribavirin on the SVR has not been fully investigated. The aim of this prospective study was to evaluate the association between ribavirin plasma level and SVR response in HCV patients treated with pegylated interferon and ribavirin. Patients and methods. Patients had plasmatic ribavirin dosage at week 4 ... [Abstract] [Full-text]


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