Impact of choice of NRTI in first-line antiretroviral therapy: a cohort analysis of stavudine vs. tenofovir

Authors

  • Alana T. Brennan,

    Corresponding author
    1. Center for Global Health & Development, Boston University, Boston, MA, USA
    2. Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
    • Corresponding Author Alana T. Brennan, Center for Global Health & Development, Boston University, Crosstown Center, 3rd Floor, 801 Massachusetts Ave, Boston, MA 02118, USA. Tel.: +1 617 414 1479; E-mail: abrennan@bu.edu

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  • Kate Shearer,

    1. Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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  • Mhairi Maskew,

    1. Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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  • Lawrence Long,

    1. Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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  • Ian Sanne,

    1. Center for Global Health & Development, Boston University, Boston, MA, USA
    2. Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
    3. Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
    4. Right to Care, Johannesburg, South Africa
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  • Matthew P. Fox

    1. Center for Global Health & Development, Boston University, Boston, MA, USA
    2. Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
    3. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
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Abstract

Objective

In April 2010, South Africa replaced stavudine with tenofovir in first-line antiretroviral therapy (ART) despite tenofovir's higher cost. We examined treatment outcomes over 24 months amongst patients initiated on tenofovir-based vs. stavudine-based first-line regimens.

Methods

Prospective cohort analysis of 3940 patients newly initiating either stavudine-based (April 2009 to March 2010) or tenofovir-based (April 2010 to March 2011) ART in Johannesburg, South Africa. Cox proportional hazards models and Fine and Gray's competing risk regression accounting for death were used to model mortality and loss to follow-up, respectively. Linear and log-binomial regression were used to evaluate associations with immunologic response and unsuppressed virus (≥400 copies/ml), respectively.

Results

About 1878 patients prescribed tenofovir and 2062 patients prescribed stavudine were included. One hundred and sixty-six (8.8%) tenofovir and 244 (11.8%) stavudine patients died. Three hundred and fifty (18.6%) tenofovir and 379 (18.4%) stavudine patients were lost to follow-up over 24 months on ART. Adjusted regression models showed tenofovir and stavudine were comparable regarding death, loss to follow-up, immunologic response and virologic status.

Conclusions

We found no difference in mortality, loss to follow-up, immunological and virologic outcomes over the first 24-months on ART associated with tenofovir compared with stavudine.

Abstract

Objectif

En avril 2010 l'Afrique du Sud a remplacé la stavudine par le ténofovir dans la thérapie antirétrovirale (ART) de première ligne, malgré un coût plus élevé du ténofovir. Nous avons examiné les résultats du traitement après 24 mois chez les patients initiés sur les schémas de première ligne à base de ténofovir versus la stavudine.

Méthodes

Analyse prospective de cohorte de 3940 patients nouvellement initiés à l’ART, basée soit sur la stavudine (avril 2009 à mars 2010) soit sur le ténofovir (avril 2010 à mars 2011) à Johannesburg, en Afrique du Sud. Les modèles de risque proportionnel de Cox et la régression de risque concurrente de Fine et Gray tenant compte des décès ont été utilisés pour modéliser respectivement la mortalité et les pertes au suivi. Les régressions linéaire et log-binomiale ont été utilisées pour évaluer respectivement les associations avec la réponse immunologique et la non suppression du virus (>400 copies/ml).

Résultats

1878 patients recevant du ténofovir et 2062 patients recevant de la stavudine été inclus. 166 (8,8%) patients ténofovir et 244 (11,8%) patients stavudine sont décédés. 350 (18,6%) patients ténofovir et 379 (18,4%) patients stavudine ont été perdus au suivi sur 24 mois sous ART. Les modèles de régression ajustés ont montré que le ténofovir et la stavudine étaient comparables en ce qui concerne le décès, la perte au suivi, la réponse immunologique et le statut virologique.

Conclusions

Nous n'avons trouvé aucune différence dans la mortalité, la perte au suivi, les résultats immunologiques et virologiques sur les 24 premiers mois sous ART, associés au ténofovir par rapport à la stavudine.

Abstract

Objetivo

En Abril 2010 Sudáfrica reemplazó la estavudina con tenofovir como primera línea de tratamiento antirretroviral (TAR), apesar del mayor precio del tenofovir. Hemos examinado los resultados del tratamiento a lo largo de 24 meses entre pacientes que iniciaron regimenes basados en tenofovir versus aquellos basados en estavudina.

Métodos

Análisis prospectivo de cohortes de 3940 pacientes comenzando TAR, bien sea basada en la estavudina (Abril 2009–Marzo 2010) o en tenofovir (Abril 2010–Marzo 2011) en Johanesburgo, Sudáfrica. Los modelos de riesgos proporcionales de Cox y la regresión de riesgos de Fine y Gray para las muertes se utilizaron para modelar la mortalidad y la pérdida durante el seguimiento, respectivamente. Mediante regresión lineal y logística binomial, se evaluaron las asociaciones con la respuesta inmunológica y viremia no suprimida (≥400 copias/ml), respectivamente.

Resultados

Se incluyeron 1878 pacientes a los que se les había prescrito tenofovir y 2062 pacientes a los que se les había prescrito estavudina. Murieron 166 (8.8%) pacientes recibiendo tenofovir y 244 (11.8%) pacientes recibiendo estavudina. Se perdieron durante el seguimiento durante los 24 meses de TAR 350 (18.6%) pacientes recibiendo tenofovir y 379 (18.4%) pacientes recibiendo estavudina. Los modelos ajustados de regresión mostraron que tenofovir y estavudina eran comparables con respecto a la muerte, la pérdida durante el seguimiento, la respuesta inmunológica y el estatus virológico.

Conclusiones

Hemos encontrado que no hay diferencias en mortalidad, pérdida durante el seguimiento, o los resultados inmunológicos y virológicos durante los primeros 24 meses de TAR, asociados al tenofovir al compararlo con la estavudina.

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