Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS

Vincent C. Marconi, Greg Grandits, Jason F. Okulicz, Glenn Wortmann, Anuradha Ganesan, Nancy Crum-Cianflone, Michael Polis, Michael Landrum, Matthew J. Dolan, Sunil K Ahuja, Brian Agan, Hemant Kulkarni

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown. Methods and Findings: Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56-3.62, p<0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p<0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/μL; p = 0.001) even after adjusting for potential confounders. Conclusions: In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.

Original languageEnglish (US)
Article numbere17956
JournalPLoS One
Volume6
Issue number5
DOIs
StatePublished - 2011

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viral load
Viral Load
Acquired Immunodeficiency Syndrome
deterioration
HIV
Recovery
therapeutics
Highly Active Antiretroviral Therapy
Therapeutics
Kinetic parameters
Linear regression
Trajectories
Linear Models
relative risk
Natural History
natural history
health services
trajectories
confidence interval
cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Marconi, V. C., Grandits, G., Okulicz, J. F., Wortmann, G., Ganesan, A., Crum-Cianflone, N., ... Kulkarni, H. (2011). Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS. PLoS One, 6(5), [e17956]. https://doi.org/10.1371/journal.pone.0017956

Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS. / Marconi, Vincent C.; Grandits, Greg; Okulicz, Jason F.; Wortmann, Glenn; Ganesan, Anuradha; Crum-Cianflone, Nancy; Polis, Michael; Landrum, Michael; Dolan, Matthew J.; Ahuja, Sunil K; Agan, Brian; Kulkarni, Hemant.

In: PLoS One, Vol. 6, No. 5, e17956, 2011.

Research output: Contribution to journalArticle

Marconi, VC, Grandits, G, Okulicz, JF, Wortmann, G, Ganesan, A, Crum-Cianflone, N, Polis, M, Landrum, M, Dolan, MJ, Ahuja, SK, Agan, B & Kulkarni, H 2011, 'Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS', PLoS One, vol. 6, no. 5, e17956. https://doi.org/10.1371/journal.pone.0017956
Marconi, Vincent C. ; Grandits, Greg ; Okulicz, Jason F. ; Wortmann, Glenn ; Ganesan, Anuradha ; Crum-Cianflone, Nancy ; Polis, Michael ; Landrum, Michael ; Dolan, Matthew J. ; Ahuja, Sunil K ; Agan, Brian ; Kulkarni, Hemant. / Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS. In: PLoS One. 2011 ; Vol. 6, No. 5.
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abstract = "Background: The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown. Methods and Findings: Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95{\%} confidence interval 1.56-3.62, p<0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p<0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/μL; p = 0.001) even after adjusting for potential confounders. Conclusions: In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.",
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AU - Wortmann, Glenn

AU - Ganesan, Anuradha

AU - Crum-Cianflone, Nancy

AU - Polis, Michael

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AU - Dolan, Matthew J.

AU - Ahuja, Sunil K

AU - Agan, Brian

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N2 - Background: The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown. Methods and Findings: Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56-3.62, p<0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p<0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/μL; p = 0.001) even after adjusting for potential confounders. Conclusions: In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.

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