Outcomes after virologic failure of first-line ART in South Africa

Richard A. Murphy, Henry Sunpath, Zhigang Lu, Neville Chelin, Elena Losina, Michelle Gordon, Douglas Ross, Aba D. Ewusi, Lynn T. Matthews, Daniel R. Kuritzkes, Vincent C. Marconi

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

OBJECTIVE: To determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART). METHODS: Baseline virologic failure was defined as HIV-1 viral load greater than 1000 copies/ml. Second-line ART was informed by results of genotype testing and selected from agents in the South-African public sector. Twenty-four week endpoints included virologic suppression and mortality. RESULTS: The cohort consisted of 141 patients (median CD4 cell count and viral load at failure of 173 cells/μl and 17 500 copies/ml). The median prior duration of initial ART was 12.0 months. At least one major resistance mutation was found in 87% of patients.After 24 weeks of follow-up, intent-to-treat virologic suppression (<50 copies/ml) was 65%, as-treated virologic suppression was 78%, the median CD4 cell count improvement was 88 cells/μl and the mortality was 6%. The median CD4 cell count at initial virologic failure among those who died was 70 cells/μl, compared to 182 cells/μl among patients who survived (P = 0.01). Patients with wild-type virus at initial failure (N = 19) had inferior outcomes after switch. The presence of nucleoside analogue resistance mutations at failure did not affect early efficacy of boosted-protease inhibitor regimens. CONCLUSIONS: Virologic monitoring linked to resistance testing helped demonstrate the efficacy of lopinavir/ritonavir-containing second-line regimens in South Africa. A switch to second-line regimens in patients with virologic failure and drug resistance has substantial and rapid immunological and clinical benefits. Resistance testing identified a high-risk group without resistance who might benefit from increased medication access and/or adherence support.

Original languageEnglish (US)
Pages (from-to)1007-1012
Number of pages6
JournalAIDS
Volume24
Issue number7
DOIs
StatePublished - Apr 2010
Externally publishedYes

Fingerprint

South Africa
CD4 Lymphocyte Count
Viral Load
Therapeutics
Lopinavir
Ritonavir
Mutation
Mortality
Public Sector
Protease Inhibitors
Nucleosides
Drug Resistance
HIV-1
Genotype
Viruses

Keywords

  • HIV-1 drug resistance
  • Resource-limited settings
  • Second-line antiretroviral therapy
  • South Africa
  • Virologic failure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Murphy, R. A., Sunpath, H., Lu, Z., Chelin, N., Losina, E., Gordon, M., ... Marconi, V. C. (2010). Outcomes after virologic failure of first-line ART in South Africa. AIDS, 24(7), 1007-1012. https://doi.org/10.1097/QAD.0b013e3283333639

Outcomes after virologic failure of first-line ART in South Africa. / Murphy, Richard A.; Sunpath, Henry; Lu, Zhigang; Chelin, Neville; Losina, Elena; Gordon, Michelle; Ross, Douglas; Ewusi, Aba D.; Matthews, Lynn T.; Kuritzkes, Daniel R.; Marconi, Vincent C.

In: AIDS, Vol. 24, No. 7, 04.2010, p. 1007-1012.

Research output: Contribution to journalArticle

Murphy, RA, Sunpath, H, Lu, Z, Chelin, N, Losina, E, Gordon, M, Ross, D, Ewusi, AD, Matthews, LT, Kuritzkes, DR & Marconi, VC 2010, 'Outcomes after virologic failure of first-line ART in South Africa', AIDS, vol. 24, no. 7, pp. 1007-1012. https://doi.org/10.1097/QAD.0b013e3283333639
Murphy RA, Sunpath H, Lu Z, Chelin N, Losina E, Gordon M et al. Outcomes after virologic failure of first-line ART in South Africa. AIDS. 2010 Apr;24(7):1007-1012. https://doi.org/10.1097/QAD.0b013e3283333639
Murphy, Richard A. ; Sunpath, Henry ; Lu, Zhigang ; Chelin, Neville ; Losina, Elena ; Gordon, Michelle ; Ross, Douglas ; Ewusi, Aba D. ; Matthews, Lynn T. ; Kuritzkes, Daniel R. ; Marconi, Vincent C. / Outcomes after virologic failure of first-line ART in South Africa. In: AIDS. 2010 ; Vol. 24, No. 7. pp. 1007-1012.
@article{7816dc7106db4b6d8faebabb451a1c6e,
title = "Outcomes after virologic failure of first-line ART in South Africa",
abstract = "OBJECTIVE: To determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART). METHODS: Baseline virologic failure was defined as HIV-1 viral load greater than 1000 copies/ml. Second-line ART was informed by results of genotype testing and selected from agents in the South-African public sector. Twenty-four week endpoints included virologic suppression and mortality. RESULTS: The cohort consisted of 141 patients (median CD4 cell count and viral load at failure of 173 cells/μl and 17 500 copies/ml). The median prior duration of initial ART was 12.0 months. At least one major resistance mutation was found in 87{\%} of patients.After 24 weeks of follow-up, intent-to-treat virologic suppression (<50 copies/ml) was 65{\%}, as-treated virologic suppression was 78{\%}, the median CD4 cell count improvement was 88 cells/μl and the mortality was 6{\%}. The median CD4 cell count at initial virologic failure among those who died was 70 cells/μl, compared to 182 cells/μl among patients who survived (P = 0.01). Patients with wild-type virus at initial failure (N = 19) had inferior outcomes after switch. The presence of nucleoside analogue resistance mutations at failure did not affect early efficacy of boosted-protease inhibitor regimens. CONCLUSIONS: Virologic monitoring linked to resistance testing helped demonstrate the efficacy of lopinavir/ritonavir-containing second-line regimens in South Africa. A switch to second-line regimens in patients with virologic failure and drug resistance has substantial and rapid immunological and clinical benefits. Resistance testing identified a high-risk group without resistance who might benefit from increased medication access and/or adherence support.",
keywords = "HIV-1 drug resistance, Resource-limited settings, Second-line antiretroviral therapy, South Africa, Virologic failure",
author = "Murphy, {Richard A.} and Henry Sunpath and Zhigang Lu and Neville Chelin and Elena Losina and Michelle Gordon and Douglas Ross and Ewusi, {Aba D.} and Matthews, {Lynn T.} and Kuritzkes, {Daniel R.} and Marconi, {Vincent C.}",
year = "2010",
month = "4",
doi = "10.1097/QAD.0b013e3283333639",
language = "English (US)",
volume = "24",
pages = "1007--1012",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - Outcomes after virologic failure of first-line ART in South Africa

AU - Murphy, Richard A.

AU - Sunpath, Henry

AU - Lu, Zhigang

AU - Chelin, Neville

AU - Losina, Elena

AU - Gordon, Michelle

AU - Ross, Douglas

AU - Ewusi, Aba D.

AU - Matthews, Lynn T.

AU - Kuritzkes, Daniel R.

AU - Marconi, Vincent C.

PY - 2010/4

Y1 - 2010/4

N2 - OBJECTIVE: To determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART). METHODS: Baseline virologic failure was defined as HIV-1 viral load greater than 1000 copies/ml. Second-line ART was informed by results of genotype testing and selected from agents in the South-African public sector. Twenty-four week endpoints included virologic suppression and mortality. RESULTS: The cohort consisted of 141 patients (median CD4 cell count and viral load at failure of 173 cells/μl and 17 500 copies/ml). The median prior duration of initial ART was 12.0 months. At least one major resistance mutation was found in 87% of patients.After 24 weeks of follow-up, intent-to-treat virologic suppression (<50 copies/ml) was 65%, as-treated virologic suppression was 78%, the median CD4 cell count improvement was 88 cells/μl and the mortality was 6%. The median CD4 cell count at initial virologic failure among those who died was 70 cells/μl, compared to 182 cells/μl among patients who survived (P = 0.01). Patients with wild-type virus at initial failure (N = 19) had inferior outcomes after switch. The presence of nucleoside analogue resistance mutations at failure did not affect early efficacy of boosted-protease inhibitor regimens. CONCLUSIONS: Virologic monitoring linked to resistance testing helped demonstrate the efficacy of lopinavir/ritonavir-containing second-line regimens in South Africa. A switch to second-line regimens in patients with virologic failure and drug resistance has substantial and rapid immunological and clinical benefits. Resistance testing identified a high-risk group without resistance who might benefit from increased medication access and/or adherence support.

AB - OBJECTIVE: To determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART). METHODS: Baseline virologic failure was defined as HIV-1 viral load greater than 1000 copies/ml. Second-line ART was informed by results of genotype testing and selected from agents in the South-African public sector. Twenty-four week endpoints included virologic suppression and mortality. RESULTS: The cohort consisted of 141 patients (median CD4 cell count and viral load at failure of 173 cells/μl and 17 500 copies/ml). The median prior duration of initial ART was 12.0 months. At least one major resistance mutation was found in 87% of patients.After 24 weeks of follow-up, intent-to-treat virologic suppression (<50 copies/ml) was 65%, as-treated virologic suppression was 78%, the median CD4 cell count improvement was 88 cells/μl and the mortality was 6%. The median CD4 cell count at initial virologic failure among those who died was 70 cells/μl, compared to 182 cells/μl among patients who survived (P = 0.01). Patients with wild-type virus at initial failure (N = 19) had inferior outcomes after switch. The presence of nucleoside analogue resistance mutations at failure did not affect early efficacy of boosted-protease inhibitor regimens. CONCLUSIONS: Virologic monitoring linked to resistance testing helped demonstrate the efficacy of lopinavir/ritonavir-containing second-line regimens in South Africa. A switch to second-line regimens in patients with virologic failure and drug resistance has substantial and rapid immunological and clinical benefits. Resistance testing identified a high-risk group without resistance who might benefit from increased medication access and/or adherence support.

KW - HIV-1 drug resistance

KW - Resource-limited settings

KW - Second-line antiretroviral therapy

KW - South Africa

KW - Virologic failure

UR - http://www.scopus.com/inward/record.url?scp=77950952552&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950952552&partnerID=8YFLogxK

U2 - 10.1097/QAD.0b013e3283333639

DO - 10.1097/QAD.0b013e3283333639

M3 - Article

C2 - 20397305

AN - SCOPUS:77950952552

VL - 24

SP - 1007

EP - 1012

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 7

ER -