Browsing by Author "Ochoa, Claudia"

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    A Randomized, Open-Label Study of a Nucleoside Analogue Reverse Transcriptase Inhibitor-Sparing Regimen in Antiretroviral-Naive HIV-Infected Patients
    (2009-03) Harris, Marianne; Côté, Hélène; Ochoa, Claudia; Allavena, Clotilde; Negredo, Eugenia; Thorne, Anona; Cahn, Pedro; Raffi, Francois; Clotet, Bonaventura; Singer, Joel; Montaner, Julio; The CTN 177 Study Team
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    Comparable Pharmacokinetics of Generic Indinavir (Inhibisam) Versus Brand Indinavir (Crixivan) When Boosted With Ritonavir
    (2005-03-01) Zala, Carlos; Alexander, Christopher; Ochoa, Claudia; Guillemi, Silvia; Ting, Lillian; Bonner, Simon; Cahn, Pedro; Harrigan, Richard P; Montaner, Julio SG
    Letter to editor about Comparable Pharmacokinetics of Generic Indinavir (Inhibisam) Versus Brand Indinavir (Crixivan) When Boosted With Ritonavir
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    Higher Rate of Toxicity With No Increased Efficacy When Hydroxyurea Is Added to a Regimen of Stavudine Plus Didanosine and Nevirapine in Primary HIV Infection
    (2002-04-01) Zala, Carlos; Salomon, Horacio; Ochoa, Claudia; Kijak, Gustavo; Federico, Andrea; Perez, Héctor; Julio SG, Montaner; Cahn, Pedro
    Summary: Twenty-four subjects presenting at a single treatment center with primary HIV infection were enrolled in a pilot study aimed to establish the possible role of hydroxyurea in this setting. Study participants were randomly assigned to receive or not to receive hydroxyurea in addition to stavudine (d4T) plus didanosine (ddI) and nevirapine (NVP). Seventy-five percent of patients without hydroxyurea had plasma HIV RNA below 50 copies/mL at 48 weeks by both intention-to-treat (ITT) and on-treatment (OT) analysis in comparison with 50% (ITT) and 67% (OT) of patients with hydroxyurea (p > .1). A median increase of >200 cells/mm3 was observed from baseline to week 48 whether or not hydroxyurea was included in the regimen. Overall, in 12 patients treated with hydroxyurea, 33 adverse events were reported versus 19 reported for 12 patients who did not receive hydroxyurea (p < .05). Our results suggest that that adding hydroxyurea to a regimen of d4T plus ddI and NVP increases toxicity without improving the antiviral effect.
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    Origin of human immunodeficiency virus type 1 quasispecies emerging after antiretroviral treatment interruption in patients with therapeutic failure
    (2002-07-15) Kijak, Gustavo H; Simon, Viviana; Balfe, Peter; Vanderhoeven, Jeroen; Pampuro, Sandra E; Zala, Carlos; Ochoa, Claudia; Cahn, Pedro; Markowitz, Martin; Salomon, Horacio
    The emergence of antiretroviral (ARV) drug-resistant human immunodeficiency virus type 1 (HIV-1) quasispecies is a major cause of treatment failure. These variants are usually replaced by drug-sensitive ones when the selective pressure of the drugs is removed, as the former have reduced fitness in a drug-free environment. This was the rationale for the design of structured ARV treatment interruption (STI) studies for the management of HIV-1 patients with treatment failure. We have studied the origin of drug-sensitive HIV-1 quasispecies emerging after STI in patients with treatment failure due to ARV drug resistance. Plasma and peripheral blood mononuclear cell samples were obtained the day of treatment interruption (day 0) and 30 and 60 days afterwards. HIV-1 pol and env were partially amplified, cloned, and sequenced. At day 60 drug-resistant variants were replaced by completely or partially sensitive quasispecies. Phylogenetic analyses of pol revealed that drug-sensitive variants emerging after STI were not related to their immediate temporal ancestors but formed a separate cluster, demonstrating that STI leads to the recrudescence and reemergence of a sequestrated viral population rather than leading to the back mutation of drug-resistant forms. No evidence for concomitant changes in viral tropism was seen, as deduced from env sequences. This study demonstrates the important role that the reemergence of quasispecies plays in HIV-1 population dynamics and points out the difficulties that may be found when recycling ARV therapies with patients with treatment failure. The different variants of human immunodeficiency virus type 1 (HIV-1) present in infected individuals have been described as quasispecies of related but distinct viruses; this plasticity of phenotype allows the virus to occupy a large adaptive landscape from which novel phenotypes may readily emerge (7, 17, 23). These variants are generated continuously due to the high replication rate of HIV-1 (50), the high frequency of recombination among viral genomes (4), and the lack of proofreading activity of the viral reverse transcriptase (RT) (41). When the selective pressure of antiretroviral (ARV) therapy is exerted on such a population, drug-resistant mutants may emerge and consequently lead to treatment failure (7, 37). The emergence of such viral variants has been extensively described and is found even in the setting of highly active ARV therapies (11, 39, 46). When this selective pressure is removed, the emergence of drug-sensitive quasispecies may be expected, as they would be predicted to have a higher fitness in a drug-free environment (9, 15, 19, 20, 22, 25, 34, 40, 42, 43). This rationale led to the many structured treatment interruption (STI) studies carried out on patients with treatment failure and multidrug-resistant viruses (10, 12, 16, 26, 45, 59). In those cohorts, a rise in plasma viral load and a concomitant fall in CD4+ cell count was observed after treatment interruption; in approximately half of the patients, drug susceptibility shifted from resistant to sensitive. However, the origin of these drug-sensitive quasispecies which emerged after STI has not been clearly defined. Understanding the mechanisms responsible for the observed changes in HIV-1 drug resistance and in viral replication after STI will provide a greater insight into HIV-1 evolution and will help define future therapeutic strategies for patients suffering treatment failure. The objective of this work was to determine the origin of drug-sensitive quasispecies arising after STI. New drug-sensitive HIV variants may be the result of point mutations (“back mutations”) in the drug-resistant quasispecies circulating immediately before STI, or they may be reemerging ancestral viral variants that had circulated before the drug-resistant viruses associated with treatment failure arose (and which had been sequestrated or suppressed during therapy). In addition we assessed whether the increase in viral load and decrease in CD4+ cell count observed after STI was associated with a change in the biological phenotype of the virus from non-syncytium-inducing/CCR5-tropic to syncytium-inducing/CXCR4-tropic. Like STI, this latter phenotype has been associated with faster replication, more rapid decline in CD4 numbers, and disease progression (6, 8, 21, 28, 56). We were able to show that viral quasispecies replicating after treatment interruption were not related to its immediate temporal ancestor but formed a separate cluster, demonstrating that STI leads to the recrudescence and reemergence of a sequestrated viral population rather than the back mutation of drug-resistant forms. No evidence for concomitant changes in viral tropism was seen. (The present study constitutes a part of Gustavo H. Kijak's doctoral work at the University of Buenos Aires.)
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    Tuberculosis and HIV: A Partnership Against the Most Vulnerable
    (2003) Cahn, Pedro; Perez, Hector; Ben, Graciela; Ochoa, Claudia
    Tuberculosis and HIV: A Partnership Against the Most Vulnerable
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    Venous and Arterial Blood Lactate in HIV-Infected Patients
    (2002-12) Zala, Carlos; Harris, Marianne; Ochoa, Claudia; Tocci, Mariel; Quercia, Romina; Mittelman, Graciela; Graciela, Héctor; Cahn, Pedro; Montaner, Julio SG
    Hyperlactataemia is increasingly recognised as a complication of nucleoside analogue-based antiretroviral therapy [1–5]. There is, however, some debate about the accuracy of peripheral venous blood lactate levels and whether these adequately reflect arterial lactate levels. This correlation has been demonstrated in the non-HIV, emergency medicine literature [6,7], but has not been studied in HIV patients receiving antiretroviral therapy. Therefore, we undertook the present study to compare venous versus arterial lactate levels in HIV patients who had consistently high random venous lactate while receiving chronic stavudine-based antiretroviral therapy.