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CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.

ABSTRACT: OBJECTIVE:To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. METHODS:CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. RESULTS:Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/?L in baseline CD4 strata 351-500, 501-650, and >650 cells/?L, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. CONCLUSIONS:Patients starting cART at high CD4 cell counts (>650 cells/?L) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death.

SUBMITTER: Wright ST

PROVIDER: S-EPMC3159689 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.

Wright Stephen T ST Carr Andrew A Woolley Ian I Giles Michelle M Hoy Jennifer J Cooper David A DA Law Matthew G MG

Journal of acquired immune deficiency syndromes (1999) 20110901 1

<h4>Objective</h4>To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter.<h4>Methods</h4>CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published ...[more]

PMID: 21654498

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Project description:BackgroundThe mitochondrial DNA (mtDNA) seems to influence in a large number of diseases, including HIV infection. Moreover, there is a substantial inter-individual variability in the CD4+ recovery in HIV-infected patients on combination antiretroviral therapy (cART). Our study aimed to analyze the association between mtDNA haplogroups and CD4+ recovery in HIV-infected patients on cART.MethodsThis is a retrospective study of 324 naïve cART patients with CD4+ <?200 cells/mm3, who were followed-up during 24 months after initiating cART. All patients had undetectable HIV viral load during the follow-up. Besides, we included 141 healthy controls. MtDNA genotyping was performed by using Sequenom's MassARRAY platform. The primary outcome variable was the slope of CD4+ recovery. Patients were stratified into two groups by the median slope value of CD4+ (9.65 CD4+ cells/mm3/month). Logistic regression analyses were performed to calculate the odds of CD4+ recovery according to mtDNA haplogroups.ResultsOur study included European HIV-infected patients within the N macro-cluster. The baseline values of CD4+ T-cells were similar between groups of patients stratified by the P50th of the slope of CD4+ T-cells recovery. Patients in the low CD4+ T-cells recovery group were older (p?=?0.001), but this variable was included in the multivariate models. When we analyzed the frequencies of mtDNA haplogroups, no significant differences between HIV-infected individuals and healthy controls were found. We did not find any significant association between mtDNA haplogroups and the slope of CD4+ T-cells recovery by linear regression analysis. However, Patients carrying haplogroup H had a higher odds of having a better CD4+ recovery (>?9.65 CD4+ cells/mm3/month) than patients without haplogroup H (p?=?0.032). The adjusted logistic regression showed that patients carrying haplogroup H had a higher likelihood of achieving a CD4+ recovery?>?9.65 CD4+ cells/mm3/month [adjusted odds ratio (aOR)?=?1.75 (95% CI?=?1.04; 2.95); p?=?0.035].ConclusionsEuropean mitochondrial haplogroup H was associated with the improved CD4+ recovery in HIV-infected patients starting cART with CD4+ <?200 cells/mm3.

Project description:BackgroundClinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals.MethodsIn this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count.Findings47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86-1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95-1·22) for threshold 200 and 1·03 (0·96-1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17-3·43) for threshold 200 and 1·24 (0·89-1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (-25·5 to 26·3) cells per μL for threshold 200 and -3·5 (-16·0 to 8·9) cells per μL for threshold 350.InterpretationDecreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies.FundingNational Institutes of Health.

Project description:BackgroundThe failure to increase CD4 T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4 T-cell homeostasis and impacts clinical evolution.MethodsWe evaluated different definitions of immunodiscordance based on CD4 T-cell counts (cutoff) or CD4 T-cell increases from nadir value (?CD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals. Unsupervised clustering was performed using relevant variables identified in the supervised approach from 191 individuals.ResultsCutoff definition of CD4 cell count 400 cells/?l performed better than any other definition in segregating immunoconcordant and immunodiscordant individuals (85% accuracy), using markers of activation, nadir and death of CD4 T cells. Unsupervised clustering of relevant variables using this definition revealed large heterogeneity between immunodiscordant individuals and segregated participants into three distinct subgroups with distinct production, programmed cell-death protein-1 (PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible number of immunodiscordant participants (22%) showed high frequency of recent thymic emigrants and low CD4 T-cell activation and death, very similar to immunoconcordant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR) PD-1 and CD45RA expression in CD4 T cells allowed reproducing subgroup segregation (81.4% accuracy). Despite sharp immunological differences, similar and persistently low CD4 values were maintained in these participants over time.ConclusionA cutoff value of CD4 T-cell count 400 cells/?l classified better immunodiscordant and immunoconcordant individuals than any ?CD4 classification. Immunodiscordance may present several, even opposite, immunological patterns that are identified by a simple immunological follow-up. Subgroup classification may help clinicians to delineate diverse approaches that may be needed to boost CD4 T-cell recovery.

Dataset Information

CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.

Publications

CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.

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