From Medscape General Medicine

eJIAS: eJournal of the International AIDS Society

Poor Efficacy and Tolerability of Stavudine, Didanosine, and Efavirenz-based Regimen in Treatment-Naive Patients in Senegal

Posted 10/09/2007

Anna Canestri, MD; Papa Salif Sow, PhD, MD; Muriel Vray, PhD; Fatou Ngom, MD; Souleymane M'boup, PhD, MD; Coumba Toure Kane, PhD; Eric Delaporte, PhD, MD; Mandoumé Gueye, MD; Gilles Peytavin, PharmD; Pierre Marie Girard, PhD, MD; Roland Landman, MD; for the ANRS 12-06/IMEA 012 Trial Study Group
Author Information

This work was presented in part at the 2nd IAS Conference on HIV Pathogenesis and Treatment, Paris, France, July 2003, Abstract 569.

Abstract

Objective: To study the effectiveness and tolerance of an antiretroviral therapy (ART) regimen composed of the antiretroviral agents (ARVs) stavudine (d4T) plus didanosine (ddI) plus efavirenz (EFV) in patients with advanced HIV infection in Senegal.

Design and methods: This was an open-label, single-arm, 18-month trial in treatment-naive patients. The primary virologic end point was the percentage of patients with plasma HIV RNA < 500 copies/mL at months 6 (M6), 12 (M12) and 18 (M18). The primary analysis was done as intent-to-treat.

Results: The staging of HIV disease, performed using the definitions of the US Centers for Disease Control and Prevention (CDC), was CDC stage B or C for all 40 recruited patients. At baseline, the mean CD4+ cell count was 133 ± 92/mcL (± standard deviation [SD]; range 1-346), and 23% of patients had CD4+ cell counts below 50/mcL. The mean baseline plasma HIV RNA level was 5.5 ± 0.4 log10 copies/mL (± SD; range 4.6-5.9). The proportion of patients with plasma HIV-1 RNA below 500 copies/mL fell during the study from 73% (95% CI [56; 85]) at M6 to 56% (95% CI [41; 73]) at M12 and 43% (95% CI [27; 59]) at M18. Plasma HIV-RNA was below 50 copies/mL in 50% of study subjects (95% CI [31; 66]) at M6, 43% (95% CI [27; 59]) at M12, and 33% (95% CI [19; 49]) at M18.

The mean increase in the CD4+ cell count was 105 ± 125/mcL (n = 38) at M3 and 186 ± 122/mcL (n = 21) at M18. Eight patients died, including 6 because of infectious complications. The last viral load (VL) value before death was < 500 copies/mL in all these patients except 1 nonadherent patient. Fifteen patients (37.5%) had peripheral neuropathy that was severe enough in 5 patients (12.5%) to require ddI and d4T discontinuation.

Conclusion: Virologic efficacy combination therapy with d4T, ddI, and EFV was measured by the percentage of patients with plasma HIV RNA values below 500 copies/mL and 50 copies/mL; for both parameters, virologic efficacy decreased during the study period. This is explained by the high mortality rate (20%) and treatment modifications due to adverse events (13%). These data strengthen the recently revised World Health Organization (WHO) guidelines advocating initiation of highly active antiretroviral therapy (HAART) before profound CD4 lymphocyte depletion occurs and avoiding HAART regimens containing d4T and ddI because of treatment-limiting side effects.

Key words: Antiretroviral therapy, d4T, ddI, efavirenz, HAART, HIV, ART-naive patient, initial ART, Senegal

Reader Comments on: Poor Efficacy and Tolerability of Stavudine, Didanosine, and Efavirenz-based Regimen in Treatment-Naive Patients in Senegal
See reader comments on this article and provide your own.

Readers are encouraged to respond to the author at landman@bichat.inserm.fr or to Paul Blumenthal, MD, Deputy Editor of MedGenMed, for the editor's eyes only or for possible publication as an actual Letter in MedGenMed via email: pblumen@stanford.edu

 
[ CLOSE WINDOW ]

References

  1. Laurent C, Diakathe N, Ngome-Gueye NF, et al. The Senegalese government's highly active antiretroviral therapy initiative: an 18-month follow-up study. AIDS. 2002;16:1363-1370. Abstract
  2. Calmy A, Clement E, Teck R, et al. Simplifying and adapting antiretroviral treatment in resource-poor settings: a necessary step to scaling-up. AIDS. 2004;18:2353-2360. Abstract
  3. Dabis F, Schecter M, Egger M, et al. Response to highly active retroviral therapy in low- and high-income countries: analysis of clinical databases. Program and abstracts of the 12th Conference on Retroviruses and Opportunistics Infections; February 22-25, 2005; Boston, Massachusetts. Abstract 23.
  4. Beck EJ, Vitoria M, Mandalia S, Crowley S, Gilks CF, Souteyrand Y. National adult antiretroviral therapy guidelines in resource-limited countries: concordance with 2003 WHO guidelines? AIDS. 2006;20:1497-502.
  5. Landman R, Schiemann R, Thiam S, et al. Once-a-day highly active antiretroviral therapy in treatment-naive HIV-1-infected adults in Senegal. AIDS. 2003;17:1017-1022. Abstract
  6. Van Leeuwen R, Katlama C, Murphy RL, et al. A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients. AIDS. 2003;17:987-999. Abstract
  7. Garcia F, Knobel H, Sambeat MA, et al. Comparison of twice-daily stavudine plus once- or twice-daily didanosine and nevirapine in early stages of HIV infection: the scan study. AIDS. 2000;14:2485-2494. Abstract
  8. Eron JJ Jr, Murphy RL, Peterson D, et al. A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II). AIDS. 2000;14:1601-1610. Abstract
  9. Gerstoft J, Kirk O, Obel N, et al. Low efficacy and high frequency of adverse events in a randomized trial of the triple nucleoside regimen abacavir, stavudine and didanosine. AIDS. 2003;17:2045-2052. Abstract
  10. Weidle PJ, Malamba S, Mwebaze R, et al. Assessment of a pilot antiretroviral drug therapy programme in Uganda: patients' response, survival, and drug resistance. Lancet. 2002;360:34-40. Abstract
  11. Scaling up antiretroviral therapy in resource-limited settings: Treatment guidelines for a public health approach, 2006 revision. Available at: http://www.who.int/hiv. Accessed September 10, 2007.
  12. Mutuluuza CK, Walker S, Kaleebu P, et al; for the DART trial. Short-term virological response to a triple nucleoside/nucleotide analogue regimen in adults with HIV infection in Africa within the DART trial. Program and abstracts of the 12th Conference on Retroviruses and Opportunistic Infections; February 22-25, 2005; Boston, Massachusetts. Abstract 22.
  13. Maggiolo F, Ripamonti D, Gregis G, et al. Once-a-day therapy for HIV infection: a controlled, randomized study in antiretroviral-naive HIV-1-infected patients. Antivir Ther. 2003;8:339-346. Abstract
  14. Molina JM, Ferchal F, Rancinan C, et al. Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients. J Infect Dis. 2000;182:599-602. Abstract
  15. Calmy A, Pinoges L, Szumilin E, et al. Generic fixed-dose combination antiretroviral treatment in resource-poor settings: multicentric observational cohort. AIDS. 2006;20:1163-1169. Abstract
[ CLOSE WINDOW ]

Related Links

[ CLOSE WINDOW ]

Author Information

Anna Canestri, MD, Institut de Médecine et d'Epidémiologie Appliquée, Bichat Claude Bernard Hospital, Paris, France

Papa Salif Sow, PhD, MD, Fann University Teaching Hospital and Centre Croix-Rouge de Traitement Ambulatoire, Dakar, Senegal

Muriel Vray, PhD, Institut Pasteur, Paris, France

Fatou Ngom, MD, Fann University Teaching Hospital and Centre Croix-Rouge de Traitement Ambulatoire, Dakar, Senegal

Souleymane M'boup, PhD, MD, Le Dantec University Teaching Hospital, Dakar, Senegal

Coumba Toure Kane, PhD, Le Dantec University Teaching Hospital, Dakar, Senegal

Eric Delaporte, PhD, MD, Institut de Recherche et Développement, Montpellier, France

Mandoumé Gueye, MD, Hospital Principal, Dakar, Senegal

Gilles Peytavin, PharmD, Pharmacology Laboratory Bichat-Claude-Bernard Hospital Paris, France

Pierre Marie Girard, PhD, MD, Institut de Médecine et d'Epidémiologie Appliquée, Bichat Claude Bernard Hospital, Paris, France

Roland Landman, MD, Institut de Médecine et d'Epidémiologie Appliquée, Bichat Claude Bernard Hospital, Paris, France

Author's email (Roland Landman, MD): landman@bichat.inserm.fr

Disclosure: Anna Canestri, MD, has disclosed no relevant financial relationships.

Disclosure: Papa Salif Sow, PhD, MD, has disclosed no relevant financial relationships.

Disclosure: Muriel Vray, PhD, has disclosed no relevant financial relationships.

Disclosure: Fatou Ngom, MD, has disclosed no relevant financial relationships.

Disclosure: Souleymane M'boup, PhD, MD, has disclosed no relevant financial relationships.

Disclosure: Coumba Toure Kane, PhD, has disclosed no relevant financial relationships.

Disclosure: Eric Delaporte, PhD, MD, has disclosed no relevant financial relationships.

Disclosure: Mandoumé Gueye, MD, has disclosed no relevant financial relationships.

Disclosure: Gilles Peytavin, PharmD, has disclosed no relevant financial relationships.

Disclosure: Pierre Marie Girard, PhD, MD, has disclosed no relevant financial relationships.

Disclosure: Roland Landman, MD, has disclosed no relevant financial relationships.

Medscape General Medicine.  2007;9(4):7.  ©2007 Medscape

 
All material on this website is protected by copyright, Copyright © 1994-2008 by Medscape. This website also contains material copyrighted by 3rd parties.
No Java Scripts variables been set