Dataset Information

Dynamic Visual Display of Treatment Response in HIV-Infected Adults.

ABSTRACT:

Background

Using a dynamic visual display, we examine the changes in human immunodeficiency virus type 1 (HIV-1) plasma viral load and CD4 cell count for 5 years after antiretroviral therapy initiation in a large cohort of patients with HIV.

Methods

Patients at a Centers for AIDS Research Network of Integrated Clinical Systems site who initiated combination antiretroviral therapy between 1 January 2000 and 31 December 2012 were followed for 5 years for HIV-1 plasma viral load, CD4 cell count, and mortality. The joint distribution of CD4 cell count and viral load over time was depicted in an animated display using a bivariate kernel smoother.

Results

Within days of therapy initiation, many patients had a suppressed viral load and their median CD4 cell count had increased. However, the median CD4 cell count remained below normal levels throughout follow-up period and the proportion of patients with high viral load occasionally increased, even years after therapy initiation.

Conclusions

The dramatic changes in viral load and CD4 cell count after therapy initiation highlight the overwhelming effectiveness of antiretroviral therapy in the modern era. However, this work also emphasizes the need for pharmaceutical or behavioral interventions to prevent virologic failure and to stimulate complete recovery of normal CD4 cell count.

SUBMITTER: Edwards JK

PROVIDER: S-EPMC4481601 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

Dynamic Visual Display of Treatment Response in HIV-Infected Adults.

Edwards Jessie K JK Cole Stephen R SR Martin Jeffrey N JN Moore Richard R Mathews W Christopher WC Kitahata Mari M Eron Joseph J JJ Saag Michael M Mugavero Michael J MJ

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20150401 1

<h4>Background</h4>Using a dynamic visual display, we examine the changes in human immunodeficiency virus type 1 (HIV-1) plasma viral load and CD4 cell count for 5 years after antiretroviral therapy initiation in a large cohort of patients with HIV.<h4>Methods</h4>Patients at a Centers for AIDS Research Network of Integrated Clinical Systems site who initiated combination antiretroviral therapy between 1 January 2000 and 31 December 2012 were followed for 5 years for HIV-1 plasma viral load, CD4 ...[more]

PMID: 25838289

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Project description:BackgroundCo-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common in sub-Saharan Africa (SSA) and can rapidly progress to cirrhosis and hepatocellular carcinoma. Recent data demonstrate ongoing HBV transmission among HIV-infected adults in SSA, suggesting that complications of HIV/HBV co-infection could be prevented with HBV vaccination. Because HBV vaccine efficacy is poorly understood among HIV-infected persons in SSA, we sought to characterize the humoral response to the HBV vaccine in HIV-seropositive Ugandan adults.MethodsWe enrolled HIV-infected adults in Kampala, Uganda without serologic evidence of prior HBV infection. Three HBV vaccine doses were administered at 0, 1 and 6 months. Anti-HBs levels were measured 4 weeks after the third vaccine dose. "Response" to vaccination was defined as anti-HBs levels ≥ 10 IU/L and "high response" as ≥ 100 IU/L. Regression analysis was used to determine predictors of response.ResultsOf 251 HIV-positive adults screened, 132 (53%) had no prior HBV infection or immunity and were enrolled. Most participants were women [89 (67%)]; median (IQR) age was 32 years (27-41), and 68 (52%) had received antiretroviral therapy (ART) for > 3 months. Median (IQR) CD4 count was 426 (261-583), and 64 (94%) of the 68 receiving ART had undetectable plasma HIV RNA. Overall, 117 (92%) participants seroconverted to the vaccine (anti-HBs ≥ 10 IU/L), with 109 (86%) participants having high-level response (anti-HBs ≥ 100 IU/L). In multivariate analysis, only baseline CD4 > 200 cells/mm3 was associated with response [OR = 6.97 (1.34-34.71), p = 0.02] and high-level response [OR = 4.25 (1.15-15.69)], p = 0.03].ConclusionHBV vaccination was effective in eliciting a protective humoral response, particularly among those with higher CD4 counts. Half of the screened patients did not have immunity to HBV infection, suggesting a large at-risk population for HBV infection among HIV-positive adults in Uganda. Our findings support including HBV vaccination as part of routine care among HIV-positive adults.

Project description:ObjectivePrior hypothesis-driven studies identified immunophenotypic characteristics associated with the control of HIV replication without antiretroviral therapy (HIV controllers) as well as with the degree of CD4 T-cell recovery during ART. We hypothesized that an unbiased 'discovery-based' approach might identify novel immunologic characteristics of these phenotypes.DesignWe performed immunophenotyping on four 'aviremic' patient groups: HIV controllers (n = 98), antiretroviral-treated immunologic nonresponders (CD4 < 350; n = 59), antiretroviral-treated immunologic responders (CD4 > 350, n = 142), and as a control group HIV-negative adults (n = 43). We measured levels of T-cell maturation, activation, dysfunction, senescence, functionality, and proliferation.MethodsSupervised learning assessed the relative importance of immune parameters in predicting clinical phenotypes (controller, immunologic responder, or immunologic nonresponder). Unsupervised learning clustered immune parameters and examined if these clusters corresponded to clinical phenotypes.ResultsHIV controllers were characterized by high percentages of HIV-specific T-cell responses and decreased percentages of cells expressing human leukocytic antigen-antigen D related in naive, central memory, and effector T-cell subsets. Immunologic nonresponders were characterized by higher percentages of CD4 T cells that were TNFα+ or INFγ+, higher percentages of activated naive and central memory T cells, and higher percentages of cells expressing programmed cell death protein 1. Unsupervised learning found two distinct clusters of controllers and two distinct clusters of immunologic nonresponders, perhaps suggesting different mechanisms for the clinical outcomes.ConclusionOur discovery-based approach confirmed previously reported characteristics that distinguish aviremic individuals, but also identified novel immunologic phenotypes and distinct clinical subpopulations that should lead to more focused pathogenesis studies that might identify targets for novel therapeutic interventions.

Dataset Information

Dynamic Visual Display of Treatment Response in HIV-Infected Adults.

Background

Methods

Results

Conclusions

Publications

Dynamic Visual Display of Treatment Response in HIV-Infected Adults.

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