Impact of Adherence on CD4 Cell Count Among HIV-Infected
Impact of Adherence on CD4 Cell Count Among HIV-Infected
Background: There have been concerns that irreversible immune damage may result if highly active antiretroviral therapy (HAART) is initiated after the CD4 cell count declines to below 350 cells/µL; however, the role of antiretroviral adherence on CD4 cell count responses has not been well evaluated.
Methods: We evaluated CD4 cell count responses of 1522 antiretroviral-naive patients initiating HAART who were stratified by baseline CD4 cell count (<50, 50-199, and ≥200 cells/µL) and adherence.
Results: Among patients starting HAART with <50 cells/µL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 200 cells/µL (interquartile range [IQR]: 130-290) for adherent patients versus 60 cells/µL (IQR: 10-130) for nonadherent patients. Similarly, among patients starting HAART with 50 to 199 cells/µL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 300 cells/µL (IQR: 180-390) versus 125 cells/µL (IQR: 40-210) for nonadherent patients. In Cox regression analyses, adherence was the strongest independent predictor of the time to a gain of ≥50 cells/µL from baseline (relative hazard [RH] = 2.88, 95% confidence interval [CI]: 2.46-3.37). Among patients with baseline CD4 cell counts <200 cells/µL, adherence was the strongest independent predictor of the time to a CD4 cell count >200 cells/µL (RH = 4.85, 95% CI: 3.15-7.47).
Conclusions: These data demonstrate that substantial CD4 gains are possible among highly advanced adherent patients and should contribute to the ongoing debate over the optimal time to initiate HAART.
The benefits of highly active antiretroviral therapy (HAART) in the management of HIV disease are well established. Through the suppression of plasma HIV-1 RNA, HAART has been shown to improve CD4 cell counts and, in turn, to decrease morbidity and mortality among HIV-infected patients. HAART presents major challenges, however, because of the more rapid emergence of drug resistance among nonadherent patients as well as the adverse effects of antiretroviral agents. As a result, the optimal time to initiate HAART is one of the most critical questions in the therapeutic management of HIV disease.
We have recently evaluated rates of disease progression stratified by baseline CD4 cell count and HIV-1 RNA levels among patients initiating HAART and found that baseline CD4 cell count was the only independent predictor of mortality. In these analyses, we found that only patients initiating therapy when the CD4 cell count had declined below 200 cells/µL were at increased risk of disease progression, a finding that has been independently verified. There have been a growing number of studies suggesting that it may not be safe to delay HAART after the CD4 cell count declines below 350 cells/µL, however. These results have led to speculation that irreversible immune damage precluding a CD4 cell count response may occur if HAART is delayed below a CD4 cell count of 350 cells/µL.
A limitation of previous studies has been that they have not been adjusted for patient adherence, and there are limited data on the relationship between CD4 cell count responses among adherent and nonadherent patients. This is an area in critical need of data, because the decision regarding when to initiate HAART relies increasingly on CD4 cell count and clinicians are increasingly reliant on CD4 cell count measures when determining the success of therapy. We therefore conducted the present analyses to evaluate CD4 cell count responses among antiretroviral-naive patients initiating HAART and the impact of patient adherence.
Background: There have been concerns that irreversible immune damage may result if highly active antiretroviral therapy (HAART) is initiated after the CD4 cell count declines to below 350 cells/µL; however, the role of antiretroviral adherence on CD4 cell count responses has not been well evaluated.
Methods: We evaluated CD4 cell count responses of 1522 antiretroviral-naive patients initiating HAART who were stratified by baseline CD4 cell count (<50, 50-199, and ≥200 cells/µL) and adherence.
Results: Among patients starting HAART with <50 cells/µL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 200 cells/µL (interquartile range [IQR]: 130-290) for adherent patients versus 60 cells/µL (IQR: 10-130) for nonadherent patients. Similarly, among patients starting HAART with 50 to 199 cells/µL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 300 cells/µL (IQR: 180-390) versus 125 cells/µL (IQR: 40-210) for nonadherent patients. In Cox regression analyses, adherence was the strongest independent predictor of the time to a gain of ≥50 cells/µL from baseline (relative hazard [RH] = 2.88, 95% confidence interval [CI]: 2.46-3.37). Among patients with baseline CD4 cell counts <200 cells/µL, adherence was the strongest independent predictor of the time to a CD4 cell count >200 cells/µL (RH = 4.85, 95% CI: 3.15-7.47).
Conclusions: These data demonstrate that substantial CD4 gains are possible among highly advanced adherent patients and should contribute to the ongoing debate over the optimal time to initiate HAART.
The benefits of highly active antiretroviral therapy (HAART) in the management of HIV disease are well established. Through the suppression of plasma HIV-1 RNA, HAART has been shown to improve CD4 cell counts and, in turn, to decrease morbidity and mortality among HIV-infected patients. HAART presents major challenges, however, because of the more rapid emergence of drug resistance among nonadherent patients as well as the adverse effects of antiretroviral agents. As a result, the optimal time to initiate HAART is one of the most critical questions in the therapeutic management of HIV disease.
We have recently evaluated rates of disease progression stratified by baseline CD4 cell count and HIV-1 RNA levels among patients initiating HAART and found that baseline CD4 cell count was the only independent predictor of mortality. In these analyses, we found that only patients initiating therapy when the CD4 cell count had declined below 200 cells/µL were at increased risk of disease progression, a finding that has been independently verified. There have been a growing number of studies suggesting that it may not be safe to delay HAART after the CD4 cell count declines below 350 cells/µL, however. These results have led to speculation that irreversible immune damage precluding a CD4 cell count response may occur if HAART is delayed below a CD4 cell count of 350 cells/µL.
A limitation of previous studies has been that they have not been adjusted for patient adherence, and there are limited data on the relationship between CD4 cell count responses among adherent and nonadherent patients. This is an area in critical need of data, because the decision regarding when to initiate HAART relies increasingly on CD4 cell count and clinicians are increasingly reliant on CD4 cell count measures when determining the success of therapy. We therefore conducted the present analyses to evaluate CD4 cell count responses among antiretroviral-naive patients initiating HAART and the impact of patient adherence.