Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa

Maya L. Petersen, Linh Tran, Elvin H. Geng, Steven J. Reynolds, Andrew Kambugu, Robin Wood, David Bangsberg, Constantin T. Yiannoutsos, Steven G. Deeks, Jeffrey N. Martin

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objective: Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa. Design: A cohort. Methods: We examined patients with confirmed virologic failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results: Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27-33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1-4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99-5.8) to that of the entire cohort, although of borderline statistical significance. Conclusion: Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality.

Original languageEnglish (US)
Pages (from-to)2097-2107
Number of pages11
JournalAIDS
Volume28
Issue number14
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

HIV
Mortality
RNA
Confidence Intervals
Therapeutics
Odds Ratio
Reverse Transcriptase Inhibitors
Uganda
Structural Models
CD4 Lymphocyte Count
South Africa
T-Lymphocytes
Weights and Measures
Incidence

Keywords

  • Antiretroviral
  • Cohort studies
  • HIV
  • HIV RNA level
  • Inverse probability weight
  • Marginal structural model
  • Time-dependent confounding
  • Treatment failure
  • Viral load

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Petersen, M. L., Tran, L., Geng, E. H., Reynolds, S. J., Kambugu, A., Wood, R., ... Martin, J. N. (2014). Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa. AIDS, 28(14), 2097-2107. https://doi.org/10.1097/QAD.0000000000000349

Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa. / Petersen, Maya L.; Tran, Linh; Geng, Elvin H.; Reynolds, Steven J.; Kambugu, Andrew; Wood, Robin; Bangsberg, David; Yiannoutsos, Constantin T.; Deeks, Steven G.; Martin, Jeffrey N.

In: AIDS, Vol. 28, No. 14, 2014, p. 2097-2107.

Research output: Contribution to journalArticle

Petersen, ML, Tran, L, Geng, EH, Reynolds, SJ, Kambugu, A, Wood, R, Bangsberg, D, Yiannoutsos, CT, Deeks, SG & Martin, JN 2014, 'Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa', AIDS, vol. 28, no. 14, pp. 2097-2107. https://doi.org/10.1097/QAD.0000000000000349
Petersen, Maya L. ; Tran, Linh ; Geng, Elvin H. ; Reynolds, Steven J. ; Kambugu, Andrew ; Wood, Robin ; Bangsberg, David ; Yiannoutsos, Constantin T. ; Deeks, Steven G. ; Martin, Jeffrey N. / Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa. In: AIDS. 2014 ; Vol. 28, No. 14. pp. 2097-2107.
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abstract = "Objective: Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa. Design: A cohort. Methods: We examined patients with confirmed virologic failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results: Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30{\%} [95{\%} confidence interval (CI) 27-33]. The majority of patients (74{\%}) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95{\%} CI 1.1-4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95{\%} CI 0.99-5.8) to that of the entire cohort, although of borderline statistical significance. Conclusion: Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality.",
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AU - Petersen, Maya L.

AU - Tran, Linh

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AU - Reynolds, Steven J.

AU - Kambugu, Andrew

AU - Wood, Robin

AU - Bangsberg, David

AU - Yiannoutsos, Constantin T.

AU - Deeks, Steven G.

AU - Martin, Jeffrey N.

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N2 - Objective: Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa. Design: A cohort. Methods: We examined patients with confirmed virologic failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results: Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27-33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1-4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99-5.8) to that of the entire cohort, although of borderline statistical significance. Conclusion: Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality.

AB - Objective: Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa. Design: A cohort. Methods: We examined patients with confirmed virologic failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results: Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27-33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1-4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99-5.8) to that of the entire cohort, although of borderline statistical significance. Conclusion: Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality.

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