Phenotypic Susceptibility to Didanosine Is Associated with Antiviral Activity in Treatment-Experienced Patients with HIV-1 Infection

Flandre, Philippe; Chappey, Colombe; Marcelin, Anne Genevieve; Ryan, Kirk; Maa, Jen-Fue; Bates, Mike; Seekins, Daniel; Bernard, Marie Charlotte; Calvez, Vincent; Molina, Jean Michel
February 2007
Journal of Infectious Diseases;2/1/2007, Vol. 195 Issue 3, p392
Academic Journal
Objective. We investigated the relationship between human immunodeficiency virus (HIV) phenotypic susceptibility to didanosine and the antiviral activity of didanosine (ddI) in the JAGUAR study. Methods. Baseline plasma HIV phenotypic susceptibility to ddI was assessed using a phenotype assay of patients randomized to receive ddI or placebo for 4 weeks in addition to their current regimen. Phenotypic susceptibility scores (PSSs) were then calculated for each sample. Associations between PSS and week 4 reductions in plasma HIV-1 RNA load or virologic response were assessed using linear regression and Jonckherre's test and the Wilcoxon and Cochran-Armitage tests, respectively. Results. In the ddI arm, a significant association between reduction in viral load and continuous PSS was observed (P<.001). Using distinct categories, an increasing fold change (FC) in susceptibility to ddI was strongly P < .0001 associated with smaller reductions in plasma HIV-1 RNA load (P<.001 ). The proportion of virologic responders P < .0001 was 83% (15/18) for patients with a ddI FC ⩽ 1.3, 50% (33/66) for patients with an FC of 1.3-2.2, and 29% (4/14) for patients with an FC ⩾ 2.2 (P = .0008). After we determined these findings, 3 ddI FC categories were defined using 1.3 and 2.2 as thresholds. Conclusions. The relationship between phenotypic susceptibility to ddI and reduction in plasma HIV-1 RNA load describes a continuum. The establishment of a lower clinical cutoff at 1.3 and an upper clinical cutoff at 2.2 are clinically relevant.


Related Articles

  • Vicriviroc in Combination Therapy with an Optimized Regimen for Treatment-Experienced Subjects: 48-Week Results of the VICTOR-E1 Phase 2 Trial. Suleiman, Jamal; Zingman, Barry S.; Diaz, Ricardo Sobhie; Madruga, Jose Valdez Ramalho; DeJesus, Edwin; Slim, Jihad; Mak, Carmen; Lee, Erin; McCarthy, Michael C.; Dunkle, Lisa M.; Walmsley, Sharon // Journal of Infectious Diseases;2/15/2010, Vol. 201 Issue 4, p590 

    Background. Agents that block the CCR5 coreceptor for human immunodeficiency virus (HIV) have demonstrated potent antiretroviral activity. In early clinical studies, the CCR5 antagonist vicriviroc proved to be a safe and effective component of combination antiretroviral therapy. Methods. This...

  • HIV-1 Virologic and Immunologic Progression and Initiation of Antiretroviral Therapy among HIV-1--Infected Subjects in a Trial of the Efficacy of Recombinant Glycoprotein 120 Vaccine. Gilbert, Peter B.; Ackers, Marta L.; Berman, Phillip W.; Francis, Donald P.; Popovic, Vladimir; Hu, Dale J.; Heyward, William L.; Sinarigil, Faruk; Shepherd, Bryan E.; Gurwith, Marc // Journal of Infectious Diseases;9/15/2005, Vol. 192 Issue 6, p974 

    The first trial of the efficacy of a human immunodeficiency virus (HIV)-1 vaccine was conducted in North America and The Netherlands between 1998 and 2003. This multicenter, randomized, placebo-controlled trial of a recombinant glycoprotein 120 vaccine included 5403 initially HIV-negative...

  • Relationship of Plasma HIV-1 RNA Dynamics to Baseline Factors and Virological Responses to Highly Active Antiretroviral Therapy in Adolescents (Aged 12--22 Years) Infected through High-Risk Behavior. Wu, Hulin; Lathey, Janet; Ruan, Ping; Douglas, Steven D.; Spector, Stephen A.; Lindsey, Jane; Hughes, Michael D.; Rudy, Bret J.; Flynn, Patricia M. // Journal of Infectious Diseases;2/15/2004, Vol. 189 Issue 4, p593 

    We characterized the viral dynamics of human immunodeficiency virus (HIV) type 1--infected adolescents receiving highly active antiretroviral therapy regimens (lamivudine [3TC]/zidovudine [ZDV]/efavirenz [EFV], 3TC/ZDV/nelfinavir [NFV], or other regimens) and studied the relationship of viral...

  • Acyclovir for Prevention of HIV Transmission. Winslow, Dean L. // Infectious Disease Alert;Mar2010, Vol. 29 Issue 6, p63 

    In a study of HIV transmission, 3,408 HIV-1 serodiscordant couples were enrolled at 14 sites in Africa. All patients had CD4+ lymphocyte counts e 250/uL, were also infected with HSV-2, and were not receiving antiretroviral therapy (ARVs). Sixty-eight percent of the HIV-1 infected partners were...

  • Impact of Therapeutic Immunization on HIV-1 Viremia after Discontinuation of Antiretroviral Therapy Initiated during Acute Infection. Kinloch-de Loes, Sabine; Hoen, Bruno; Smith, Don E.; Autran, Brigitte; Lampe, Fiona C.; Phillips, Andrew N.; Li-Ean Goh; Andersson, Jan; Tsoukas, Christos; Sonnerborg, Anders; Tambussi, Giuseppe; Girard, Pierre-Marie; Bloch, Mark; Battegay, Manuel; Carter, Nick; El Habib, Raphaelle; Theofan, Georgia; Cooper, David A.; Perrin, Luc // Journal of Infectious Diseases;8/15/2005, Vol. 192 Issue 4, p607 

    Background. Treatment strategies that would induce durable virological control of human immunodeficiency virus (HIV)-1 in the absence of continued antiretroviral therapy (ART) are highly desirable. Methods. We assessed, in a randomized, double-blind, placebo-controlled trial, whether the...

  • Symptom Burden in HIV-Infected Adults at Time of HIV Diagnosis in Rural Uganda. Wakeham, Katie; Harding, Richard; Bamukama-Namakoola, Doreen; Levin, Jonathan; Kissa, John; Parkes-Ratanshi, Rosalind; Muzaaya, Godfrey; Grosskurth, Heiner; Lalloo, David G. // Journal of Palliative Medicine;Apr2010, Vol. 13 Issue 4, p375 

    Purpose: This study aimed to measure symptom burden prior to antitetroviral therapy (ART) initiation in a population of adults with low CD4 presenting for human immunodeficiency virus (HIV) care and treatment in Uganda, and to explore the relationship between World Health Organization (WHO)...

  • Body Fat and Other Metabolic Effects of Atazanavir and Efavirenz, Each Administered in Combination with Zidovudine plus Lamivudine, in Antiretroviral- Naive HIV- Infected Patients. Jemsek, Joseph G.; Arathoon, Eduardo; Arlotti, Massimo; Perez, Carlos; Sosa, Nestor; Pokrovskiy, Vadim; Thiry, Alexandra; Soccodato, Michael; Noor, Mustafa A.; Giordano, Michael // Clinical Infectious Diseases;1/15/2006, Vol. 42 Issue 2, p273 

    Background. Protease inhibitor treatment of human immunodeficiency virus (HIV)-infected individuals has been linked to the development of lipodystrophy. The effects of atazanavir on body fat distribution and related metabolic parameters were examined in antiretroviral-naive patients. Methods....

  • ART Suppresses Plasma HIV-1 RNA to a Stable Set Point Predicted by Pretherapy Viremia. Maldarelli, Frank; Palmer, Sarah; King, Martin S.; Wiegand, Ann; Polis, Michael A.; Mican, JoAnn; Kovacs, Joseph A.; Davey, Richard T.; Rock-Kress, Diane; Dewar, Robin; Shuying Liu; Metcalf, Julia A.; Rehm, Catherine; Brun, Scott C.; Hanna, George J.; Kempf, Dale J.; Coffin, John M.; Mellors, John W. // PLoS Pathogens;Apr2007, Vol. 3 Issue 4, pe46 

    Current antiretroviral therapy is effective in suppressing but not eliminating HIV-1 infection. Understanding the source of viral persistence is essential for developing strategies to eradicate HIV-1 infection. We therefore investigated the level of plasma HIV-1 RNA in patients with viremia...

  • Keeping quiet: microRNAs in HIV-1 latency. Han, Yefei; Siliciano, Robert F. // Nature Medicine;Oct2007, Vol. 13 Issue 10, p1138 

    The article presents information on a research regarding the role of microRNAs in the latency of HIV-1 in resting T cells. The study found that the findings could be used in the development of antiretroviral therapies to clear the body of virus. The study found that the state of latency may...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics