Enhanced CD4+ T-Cell Recovery with Earlier HIV-1 Antiretroviral Therapy (original) (raw)
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Clinical Infectious Diseases, 2005
Background. The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)-infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration. Methods. Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load !1000 copies/mL for у5 years. CD4 T cell recovery was stratified by CD4 T cell count 5 years after initiation of ART (у500 cells/mL was defined as a complete response, and !500 cells/mL was defined as an incomplete response). Determinants of incomplete responses and clinical events were evaluated using logistic regression and survival analyses. Results. The median CD4 T cell count increased from 180 cells/mL at baseline to 576 cells/mL 5 years after ART initiation. A total of 35.8% of patients were incomplete responders, of whom 47.6% reached a CD4 T cell plateau !500 cells/mL. Centers for Disease Control and Prevention HIV-1 disease category B and/or C events occurred in 21% of incomplete responders and in 14.4% of complete responders (). Older age (adjusted P 1 .05 odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21-2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28-0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19-4.81) were significantly associated with a CD4 T cell count !500 cells/mL at 5 years. The median increases in CD4 T cell count after 3-6 months of ART were smaller in incomplete responders () and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% P ! .001 sensitivity and 72% specificity. Conclusion. Individuals with incomplete CD4 T cell recovery to !500 cells/mL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3-6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocytes. The key feature of untreated HIV-1 infection is the progressive depletion of CD4 T lymphocytes. The major achievement of potent antiretroviral therapy (ART)
Evaluation of the Trend of CD4 Cell Count Over Time in Case of HIV/AIDS Patients under ART Follow-up
Journal of Scientific Research and Reports, 2019
Background: Globally 36.7 million people living with HIV, 1.8 million new HIV infection, and 1 million AIDS-related deaths in 2016.Patient mortality was high during the first 6 months after therapy for all patient subgroups and exceeded 40 per 100 patient years among patients who started treatment at low CD4 count. The aim this study was to evaluate the trend of CD4 cell count over time and to determine the progress of patient characteristics measured at baseline on CD4 cell count of HIV-infected patients who were under ART treatment in Arba Minch Hospital. Methods: This study was retrospective follow up study using data extracted from medical records, patient interviews, and laboratory work-up. The study was employed among 550 adult patients that were selected by simple random sampling. The continuous outcome variable CD4 cell count has measured at months 0, 6, 12, 18, and 24. Longitudinal data analysis were used because the set of measurements on one patient tend to be correlated,...
AIDS, 2018
Objective: To assess CD4 recovery after combined antiretroviral therapy (cART) initiation with sustained virologic control. Design: Cohort study based on the French Hospital Database on HIV (FHDH-ANRS CO4). Methods: We selected naïve HIV-1-infected individuals initiating cART between 2006 and 2014 with CD4 counts < 500/mm 3 who achieved virologic control, defined as two consecutive viral loads < 50 copies/mL. We estimated the cumulative incidence of CD4 recovery ≥ 500 cells/mm 3 and identified associated factors, considering "virologic failure", "loss to follow-up", and "death" as competing events. Results: We analyzed 6050 individuals with a median follow-up of 14.2 months since virologic control. The cumulative incidence for CD4 recovery after six years of virologic control reached 69.7%. The main factor associated with CD4 recovery was the CD4 count at treatment initiation (subdistribution hazard ratio (sHR): 9.64, 95% confidence interval (95% CI): 8.12-11.43 for CD4 counts between 350 and 500 cells/mm 3 compared with CD4 counts < 100 cells/mm 3). A higher CD4/CD8 ratio at initiation was also independently associated with a higher probability of CD4 recovery (sHR: 1.67 (95% CI: 1.34-2.09) for a CD4/CD8 ratio ≥ 1.00 vs < 0.30). Higher viral load at initiation was also associated with a higher probability of CD4 recovery, whereas time to viral suppression was not. Conclusion: After six years of sustained virologic control, a large majority of the population achieved CD4 recovery. A higher CD4 count at initiation was a strong
Archives of Internal Medicine, 2003
Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-1 infection allows recovery of CD4 T lymphocytes. Few studies have explored the long-term T-lymphocyte responses to HAART. Plasma HIV-1 RNA levels and CD4 and CD8 T-lymphocyte counts were longitudinally analyzed over 4 years in 2235 participants of the Swiss HIV Cohort, commencing HAART between 1996 and 1997. The CD4 T-lymphocyte count increase, the percentage of individuals with a CD4 T-lymphocyte count of 500/microL or greater and less than 200/microL, and the determinants of CD4 T-lymphocyte recovery were evaluated in individuals treated with continuous (CONT; n = 985) and discontinuous (DISCONT; n = 1250) HAART. At 4 years, 69.5% of subjects (CONT, 84.5%; DISCONT, 53.6%; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001) showed HIV-1 RNA levels below 400 copies/mL, while the median CD4 T-lymphocyte count increased from 190/microL to 423/microL (CONT, 486/microL; DISCONT, 343/microL; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). Of the 2235 participants, 38.8% (CONT, 47.7%; DISCONT, 29.4%; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001) reached a CD4 T-lymphocyte count of 500/microL or greater, but in 15.6%, CD4 T-lymphocyte count remained below 200/microL (CONT, 5.9%; DISCONT, 25.9%; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). Larger increases in CD4 T-lymphocyte count were associated with higher baseline HIV-1 RNA, a larger percentage of undetectable HIV-1 RNA levels, lower baseline CD8 T-lymphocyte count, and younger age. Individuals reaching a CD4 T-lymphocyte count of 500/microL or greater at 4 years were characterized by higher nadir and baseline CD4 T-lymphocyte counts and a more sustained reduction of HIV-1 RNA levels. At 4 years, only 39% of individuals treated with HAART reached a CD4 T-lymphocyte count of 500/microL or greater, and 16% with CD4 T-lymphocyte counts less than 200/microL remained susceptible to opportunistic infections. Treatment interruptions, a poor virologic response, and older age were the major factors negatively affecting the recovery of CD4 T lymphocytes.
PLOS ONE
Objectives To analyse the correlation and concordance between aCD4, CD4%, CD4/CD8, their intrapatient variability, and to compare the immune recovery (IR) rates based on the three parameters in HIV-infected patients after starting antiretroviral therapy. Methods From a prospectively followed cohort, patients who maintained HIV-RNA suppression in �95% of the determinations throughout the follow-up were selected. IR was defined as aCD4 >650/μl, CD4% �38% or CD4/CD8 �1. Results A total of 1164 patients with a median follow-up of 5 years were analysed. The increases in aCD4, CD4% and CD4/CD8 were highest during the first year and considerably lower thereafter regardless of baseline aCD4. The annual increases in aCD4 showed poor correlations with those of CD4% (r = 0.143-0.250) and CD4/CD8 (r = 0.101-0.192) but were high between CD4% and CD4/CD8 (r = 0.765-0.844; p<0.001). The median intra-annual coefficients of variation for aCD4, CD4/CD8 and CD4% were 12.5, 8.5 and 6.6, respectively. After five years, 66.7%, 41.6% and 42.1% of the patients reached aCD4 >650/μl, CD4% �38%, and CD4/CD8 �1, respectively, while only 31% achieved both aCD4 and CD4/CD8 target values. Conclusions The increases in aCD4 poorly correlate with those of CD4% and CD4/CD8. IR rates based on aCD4 significantly overstate those obtained by CD4% and CD4/CD8. CD4% and CD4/ CD8 are more stable markers than aCD4 and should be taken into account to monitor the IR after treatment initiation.
AIDS, 2007
a and the CASCADE Collaboration Objective: To investigate the effect of a short course of HAART during primary HIV infection (PHI) on rate of CD4 cell and viral load change. Methods: Data following HAART cessation from 89 individuals (seroconverting 1999-2003) who chose to take a 3 month course of HAART at PHI were compared with 179 untreated controls in CASCADE, using linear and nonlinear random effects models. Participants were non-randomized but frequency matched for age, sex, risk factor, year of seroconversion and presentation within the first 6 months of seroconversion. Time to CD4 cell count < 350 cells/ml and initiation of clinically indicated antiretroviral therapy (ART) were also compared as competing risks. Results: The rate of CD4 cell decline following therapy cessation appeared significantly slower among treated participants than untreated controls: losses of 51 cells/ml [95% confidence interval (CI), 32-69] and 77 cells/ml (95% CI, 65-89), respectively, 3 years after seroconversion (P ¼ 0.011). Based on extrapolated data, viral loads also differed significantly at this point (4.09 and 4.53 copies/ml, respectively). At 2 years, there was no significant difference in mean viral load levels: 4.31 copies/ml (95% CI, 4.14-4.48) and 4.47 copies/ml (95% CI, 4.28-4.66), respectively. CASCADE seroconverters were more likely to reach CD4 cell count < 350 cells/ml or initiate clinically indicated ART (hazard ratio, 1.45; 95% CI, 1.02-2.05; P ¼ 0.039). Conclusion: A short course of ART at PHI may delay CD4 cell decline. Confirmation of this requires a randomized clinical trial powered to address definitively the role of ART intervention in PHI (currently underway through SPARTAC).
Background Antiretroviral therapy (ART) initiation is now recommended irrespective of CD4 count. However data on the relationship between CD4 count at ART initiation and loss to follow-up (LTFU) are limited and conflicting. Methods We conducted a cohort analysis including all adults initiating ART (2008–2012) at three public sector sites in South Africa. LTFU was defined as no visit in the 6 months before database closure. The Kaplan-Meier estimator and Cox’s proportional hazards models examined the relationship between CD4 count at ART initiation and 24-month LTFU. Final models were adjusted for demographics, year of ART initiation, programme expansion and corrected for unascertained mortality. Results Among 17 038 patients, the median CD4 at initiation increased from 119 (IQR 54–180) in 2008 to 257 (IQR 175–318) in 2012. In unadjusted models, observed LTFU was associated with both CD4 counts <100 cells/μL and CD4 counts ≥300 cells/μL. After adjustment, patients with CD4 counts ≥300 cells/μL were 1.35 (95% CI 1.12 to 1.63) times as likely to be LTFU after 24 months compared to those with a CD4 150–199 cells/μL. This increased risk for patients with CD4 counts ≥300 cells/μL was largest in the first 3 months on treatment. Correction for unascertained deaths attenuated the association between CD4 counts <100 cells/μL and LTFU while the association between CD4 counts ≥300 cells/μL and LTFU persisted. Conclusions Patients initiating ART at higher CD4 counts may be at increased risk for LTFU. With programmes initiating patients at higher CD4 counts, models of ART delivery need to be reoriented to support long-term retention.