Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count

OBJECTIVE: To assess the absolute rate of AIDS and death in antiretroviral therapy (ART)-naive patients with a high CD4 cell count. Such information would be helpful in the design of a trial investigating early initiation of ART. DESIGN: Analysis of data from an ongoing HIV cohort study. METHODS: The rate of (severe) AIDS or death and death alone was evaluated in ART-naive patients according to the current CD4 cell count, focusing on CD4 cell counts > or = 350 cells/microl among patients in the UK CHIC Study. RESULTS: In a total of 30 313 person-years of follow-up, there were 1557 AIDS or death events. The rate of AIDS or death in persons with most recent CD4 cell count 350-499, 500-649 and > 650 cells/microl was 2.49, 1.54 and 0.96 per 100 person-years, respectively. The rate ratio for those with CD4 cell count 500-649 cells/microl compared with those with CD4 cell count > or = 650 cells/microl was 1.55 [95% confidence interval (CI), 1.11-2.17; P = 0.01]. In a Poisson regression model based on person years with CD4 cell count > or = 350 cells/microl , there was a strong effect of CD4 cell count on rate of AIDS or death (rate ratio, 0.84; 95% CI, 0.76-0.93; P = 0.001), independent of viral load and age. CONCLUSIONS: The trend of decreasing rate of AIDS and death with higher CD4 cell count is present throughout the CD4 cell count > or = 350 cells/microl range in ART-naive people.     

CD4 count and viral load time-courses in patients treated with highly active antiretroviral therapy and association with the CDC staging system

Objectives

The aim of the study was to analyse CD4 cell count and viral load dynamics in patients undergoing antiretroviral therapy and their association with the Centers for Disease Control and Prevention (CDC) classification system.

Methods

CD4 cell count and viral load were determined in 2982 patients who were classified according to clinical and immunological CDC stages. Measurements were carried out at baseline and at the 3rd, 6th and 12th months.

Results

Clear differences in the immunological and virological responses to therapy were observed depending on the CDC stage, with better results associated with less advanced stages. There was a marked parallelism in the CD4 cell count curves of the different CDC stages over the year of follow up, in both naïve and experienced patients, indicating that the increase in CD4 cell count at each time‐point was similar for all clinical and immunological CDC stages. However, as the baseline values were closely associated with CDC stage, the CD4 cell counts finally reached were clearly dependent on CDC stage. The highest virological responses were observed during the initial 3 months, particularly in naïve patients, but whereas naïve patients showed additional increases up to the 6th month experienced patients reached a plateau at the 3rd month. The CD4 increases were also higher during the initial 3 months but persisted during the year of follow‐up.

Conclusion

Both clinical and immunological CDC stages at baseline are highly predictive of the immunological and virological response to therapy, a finding that could have clinical implications.

     

Full suppression of viral load is needed to achieve an optimal CD4 cell count response among patients on triple drug antiretroviral therapy

OBJECTIVE: To characterize the relationship between plasma viral load (pVL) suppression and triple drug antiretroviral therapy, and the accompanying changes in CD4 cell counts. METHOD: Retrospective study of 465 participants in a HIV/AIDS Treatment Program who initiated triple drug therapy between August 1996 and May 1998. Participants were divided into three groups according to their pVL response: (i) non-responders (NR; n = 112) exhibited pVL persistently > 500 copies/ml over the study period; (ii) partial responders (PR; n = 100) achieved a pVL < 100 copies/ml at least once and subsequently rebounded to > 500 copies/ml; and (iii) full responders (FR; n = 253) achieved a pVL < 500 copies/ml and sustained this level for the remainder of the study period. For each group, the accompanying changes in absolute and fractional CD4 cell counts were evaluated. RESULTS: The median net change in pVL per person from baseline to the end of the observation period was -0.37, -2.27, and -2.56 log10 copies/ml for NR, PR and FR, respectively. During weeks 68-83, the median CD4 cell count (x 10(6) cells/l) was 150 [interquartile range (IQR) 90-370], 380 (IQR 300-480) and 525 (IQR 305-705) for NR, PR and FR, respectively. Median changes in CD4 cells (x 10(6) cells/l) were -20 (IQR -90 to 40), 150 (IQR 30-250) and 240 (IQR 110-365) for NR, PR, and FR, respectively. The net percentage change in CD4 cells per person was 0% (IQR -34-31), 54% (IQR 6-160), and 83% (IQR 39-173) for NR, PR, and FR, respectively. By weeks 68-83, the median fractional CD4 cells was 0.16 (IQR 0.07-0.22), 0.22 (IQR 0.15-0.28), and 0.26 (IQR 0.17-0.34) for NR, PR and FR respectively. CONCLUSIONS: An optimal CD4 cell count response appears to be coupled with continued pVL suppression. Our data indicate that maximal suppression of viral replication should remain the primary goal of therapy.     

Spontaneous control of viral load and CD4 cell count progression among HIV-1 seroconverters

OBJECTIVES: To identify factors associated with sustained undetectable viraemia after HIV-1 seroconversion in treatment-naive patients, and to describe concomitant CD4 cell count progression. METHODS: Seroconverters enrolled in CASCADE were assumed to control viraemia if at least two consecutive viral load measurements were < 400/500 copies/ml without treatment. Factors associated with undetectable viraemia were identified through a logistic regression. A joint model was used to describe simultaneously the CD4 cell count progression during and after that period and to identify factors associated with sustained undetectable viraemia. RESULTS: Of 2176 seroconverters, 145 (6.7%) spontaneously controlled viraemia. Women were more likely than men to achieve undetectable viraemia [adjusted odds ratio (OR), 2.12; 95% confidence interval (CI), 1.49-3.12] unlike patients who reported a symptomatic primary infection (adjusted OR, 0.58; 95% CI, 0.36-0.94). AIDS and death rates were significantly lower in patients achieving undetectable viraemia than in the others. The median period of undetectable viraemia was 11.2 months; on average, CD4 cell counts remained stable during that period, and decreased with a mean rate of 5 cells/microl per month thereafter. High CD4 cell count at the beginning of undetectable viraemia and non-symptomatic primary infection favoured the preservation of undetectable viraemia. CONCLUSION: A small proportion of seroconverters appeared to be able to control HIV viraemia spontaneously, mostly those without seroconversion illness and within a few years following seroconversion; this is associated with the benefits of slower CD4 cell count decline and improved long-term prognosis. Such persons should be targeted for in depth investigation.     

Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy

OBJECTIVE: To determine the extent to which HIV-infected patients, including those with advanced immunodeficiency, can reverse peripheral CD4 T-cell depletion while maintaining long-term viral suppression on highly active antiretroviral therapy. DESIGN: Cohort study. PARTICIPANTS: Four-hundred and twenty-three HIV-infected patients who initiated HAART prior to 1998 and achieved a viral load 1000 copies/ml. MAIN OUTCOME MEASURE: CD4 count changes. RESULTS: Among patients who maintained plasma HIV RNA levels /= 350 x 10(6)/l, respectively (all gains were significantly greater than zero; P < 0.05). Among those with a pre-therapy CD4 count of < 50 x 10(6)/l, 88% achieved a CD4 cell count of >/= 200 x 10(6)/l and 59% achieved a count of >/= 350 x 10(6)/l by year 4. Factors associated with increased CD4 cell count gains from month 3 to year 4 included lower pre-therapy CD4 cell count, younger age, female sex, and infrequent low-level viremia (versus sustained undetectable viremia). CONCLUSIONS: Most patients who achieve and maintain viral suppression on HAART continue to experience CD4 T-cell gains through 4 years of therapy. The immune system's capacity for CD4 T lymphocyte restoration is not limited by low pre-therapy CD4 counts.     

Characterization of nef gene of HIV type 1 in highly active antiretroviral therapy treated AIDS patients with discordance between viral load and CD4+ T cell counts

The advent of highly active antiretroviral therapy (HAART) has been effective in the treatment of AIDS patients. However, after receiving this treatment for various periods of time, there is in some patients a significant increase in plasma viral load without a decrease in CD4+ T cell count. Our study involved nine such AIDS patients showing this discordance. We characterized changes in the nef gene of plasma HIV-1 isolated from these patients. Viral RNA was extracted from patient plasma, amplified by RT-PCR, cloned, and sequenced. Three sequences from each patient were obtained. The sequences were aligned and compared with other strains of HIV-1. Various substitutions were seen in most patients; however, two patients showed unique insertions of different sizes that are probably due to HAART.     

HIV感染者检测病毒载量和CD4淋巴细胞计数的关系

目的 探讨HIV感染者抗逆转录病毒治疗前血液标本HIV病毒载量(VL)及CD4淋巴细胞计数的关系.方法 采用RT-PCR法和流式细胞分析系统,对重庆地区部分HIV病毒感染者169份血液标本的VL和CD4平行检测结果进行分析.结果 169份标本中VL能被定量的有160份(94.7%),其结果6.0×103~2.80×107拷贝/ml之间,CD4细胞计数3~836个/μl.经相关性分析,CD4细胞值与VL对数值呈负相关(r=-0.43,P<0.01).结论平行检测VL和CD4细胞数可帮助了解疾病进展状况,选择开始治疗的时机.     

Unexpected CD4 cell count decline in patients receiving didanosine and tenofovir-based regimens despite undetectable viral load

BACKGROUND: We recently observed a significant CD4 cell count decline in patients receiving didanosine (ddI) 400 mg, tenofovir (TDF) and nevirapine (NVP), despite virological suppression. METHODS: We identified from our computerized patient database subjects who initiated combinations containing ddI and/or TDF for reasons other than virological failure, including simplification or intolerance. Changes in total, CD4+ and CD8+ lymphocyte counts since the initiation of therapy were analysed retrospectively. Plasma concentration of ddI was prospectively determined in eight of these patients receiving ddI 400 mg + TDF + NVP and 3 weeks after a ddI dosage reduction. RESULTS: A total of 302 patients were studied. A significant decrease in CD4 and CD8 and in total lymphocyte counts was only seen in subjects receiving ddI standard dose + TDF-containing regimens, despite the maintenance of viral suppression. More than 50% of these patients showed a decline of more than 100 CD4 cells at 48 weeks. In contrast, subjects not receiving ddI + TDF together experienced the expected progressive increase in CD4 T-cell counts. Plasma levels of ddI were elevated in all patients receiving the standard ddI dose + TDF. DdI plasma levels significantly decreased when patients weighting > 60 kg reduced ddI dose to 250 mg, achieving similar levels to those generated by ddI 400 mg without TDF. CONCLUSIONS: Co-administration of ddI at standard doses plus TDF appears to exert a deleterious effect on CD4 and CD8 counts. Although lymphocyte toxicity related to excessive ddI plasma levels could explain our findings, other mechanisms cannot be excluded. Pharmacokinetic data suggest ddI dose reduction when coadministered with TDF.     

Reliability and validity of self-reported CD4 lymphocyte count and viral load test results in people living with HIV/AIDS

Self-reporting is a common, convenient, and inexpensive method for collecting health status information in HIV/AIDS research, but the reliability and validity of these data remain suspect. HIV-positive persons (n=174) completed self-report measures of demographics, health status, and health literacy, and provided permission to collect CD4 cell counts and viral load results from provider charts. Clinically meaningful categories of CD4 cell counts were reliably and validly assessed using self-report measures. Self-reported viral load, however, demonstrated only marginally acceptable reliability and validity, with the greatest validity occurring for recall of undetectable viral load. Self-reported health status was most reliable and valid for persons with higher levels of education and literacy. CD4 cell counts can therefore be reliably and validly assessed through self-reporting, particularly when collected in clinically meaningful units from persons with higher education. Self-reported viral load should be interpreted with caution and is most reliable when dichotomized into detectable/undetectable categories.     

Correlation between CD4 cell counts and cellular and plasma viral load in HIV-1-seropositive individuals.

We conducted a study of 152 HIV-1-seropositive individuals in order to evaluate the possible correlations between the isolation of HIV from peripheral blood mononuclear cells or from plasma and CD4 cell counts. HIV was isolated from only 36% of plasma samples, and the isolation rate was closely related to CD4 cell counts, increasing gradually from 0% in subjects with greater than 800 x 10(6)/l CD4 cells to 88% in those with less than 100 x 10(6)/l CD4 cells. In contrast, HIV was isolated from 92% of cell samples (99% in subjects with less than 900 x 10(6)/l CD4 cells, 46% in those with CD4 counts greater than or equal to 900 x 10(6)/l). Since most cell samples were positive, a scoring method was designed to quantify the cellular viral load. The results obtained demonstrated that the cellular viral load was closely related to CD4 counts. We also found that the cellular viral load was higher in subjects with either positive plasma isolation or positive p24 antigenaemia. The measurement of the cellular viral load by this scoring method appears to be useful for the management of HIV-seropositive individuals and for the evaluation of therapeutic trials.