Immunologic Responses Associated with 12 Weeks of Combination Antiretroviral Therapy Consisting of Zidovudine, Lamivudine, and Ritonavir: Results of AIDS Clinical Trials Group Protocol 315

Lederman, Michael M.; Connick, Elizabeth; Landay, Alan; Kuritzkes, Daniel R.; Spritzler, John; Clair, Marty St.; Kotzin, Brian L.; Fox, Lawrence; Chiozzi, Margo Heath; Leonard, John M.; Rousseau, Franck; Wade, Michael S.; Roe, Joana D'Arc; Martinez, Ana; Kessler, Harold A.

doi:10.1086/515591

Cited by 397 publications

(264 citation statements)

References 37 publications

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“…Several studies have reported increased rates of viral replication and decreases in TCD 4 + cell counts during acute phases of TB [13,[48][49][50][51]. TCD 8 + cell counts had lower values in patients with disseminated TB at study entry; however, the differences were not significant.…”

Section: Discussionmentioning

confidence: 94%

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Clinical forms and outcome of tuberculosis in HIV-infected patients in a tertiary hospital in São Paulo - Brazil

Klautau¹,

Kuschnaroff²

2005

Braz J Infect Dis

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Section: Discussionmentioning

confidence: 94%

“…It is known that M. tuberculosis activates HIV expression [49], and that it may increase pathogenicity and speed up disease progression to AIDS [13].…”

Section: Discussionmentioning

confidence: 99%

Clinical forms and outcome of tuberculosis in HIV-infected patients in a tertiary hospital in São Paulo - Brazil

Klautau¹,

Kuschnaroff²

2005

Braz J Infect Dis

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“…Co-expression of CD45RA and CD62L was used to identify the naive T cell subsets. 6,57 At baseline, the median number of CD45RA and CD62L positive (naive) CD4 T cells was 19.5 cells/ml (range 2 ± 392, standard error 37.4), which increased to 114 (range 5 ± 346, standard error 35.3) at day 60 (overall P=0.02). At day 180, median 58.5 (range 13 ± 113, standard error=11.9) naive CD4 T cells/ml were present.…”

Section: Immune Reconstitution Following Therapymentioning

confidence: 98%

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection

et al. 1999

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T cells from HIV infected patients undergo spontaneous apoptosis at a faster rate than those from uninfected patients, are abnormally susceptible to activation induced cell death (AICD), and undergo increased apoptosis in response to Fas receptor ligation. These observations have led to the hypothesis CD4 T cell apoptosis may be a mechanism of CD4 T cell depletion and the pathogenesis of AIDS. Successful treatment of HIV infected patients is accompanied by quantitative and qualitative improvements in immune function reflecting at least partial reversibility of the underlying pathogenesis of HIV. In this report we correlate improvements in markers of immune function with a decrease in apoptosis, and changes in its regulation. Therapy with nelfinavir plus saquinavir in combination with two nucleoside analogue inhibitors of reverse transcriptase dramatically reduces plasma viremia and increases CD4 T cell counts. Coincident with these improvements, CD38 and HLA-DR coexpression on both CD4 and CD8 T cells decrease, and CD45RA and CD62L coexpression increase. Furthermore, spontaneous apoptosis decreases in both CD4 and CD8 T cells (CD4 apoptosis 17.4 vs 2.6%, P=0.005; CD8 apoptosis 15.0 vs 1.0%, P50.001), as does both Fas mediated apoptosis (CD4 apoptosis 19.0 vs 3.5%, P=0.03; CD8 apoptosis 13.7 vs 1.5%, P=0.002) and CD3 induced AICD (CD4 apoptosis 13.7 vs 3.2%, P=0.001; CD8 apoptosis 29 vs 2.2%, P=0.08). Changes in apoptosis are not associated with changes in Fas receptor expression, but are significantly correlated with changes in activation marker profiles. Although this suggests a possible regulatory role for the apoptosis inhibitory protein FLIP, direct assessment did not reveal quantitative differences in FLIP expression between apoptosis resistant PBL's from HIV negative patients, and apoptosis sensitive PBL's from HIV positive patients. These findings support the hypothesis that apoptosis mediates HIV induced CD4 T cell depletion, but indicate the need for further studies into the molecular regulation of HIV induced apoptosis.

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“…For example, it is not known whether the recovery of CD4 cells is purely a consequence of viral load suppression or that ART (or different ART regimens) may impact CD4 directly or through other pathways. 20 Our primary aim is to model the trajectories of CD4 over time as a function of the type of ART received and viral load. We use regression models to investigate the association between ART and CD4 restoration, while adjusting the possible impact of the antiviral effect.…”

Section: The Dataset and Research Objectivesmentioning

confidence: 99%

A mechanistic nonlinear model for censored and mismeasured covariates in longitudinal models, with application in AIDS studies

Zhang

Wong

2017

Statistics in Medicine

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When modeling longitudinal data, the true values of time-varying covariates may be unknown because of detection-limit censoring or measurement error.A common approach in the literature is to empirically model the covariate process based on observed data and then predict the censored values or mismeasured values based on this empirical model. Such an empirical model can be misleading, especially for censored values since the (unobserved) censored values may behave very differently than observed values due to the underlying data-generation mechanisms or disease status. In this paper, we propose a mechanistic nonlinear covariate model based on the underlying data-generation mechanisms to address censored values and mismeasured values. Such a mechanistic model is based on solid scientific or biological arguments, so the predicted censored or mismeasured values are more reasonable. We use a Monte Carlo EM algorithm for likelihood inference and apply the methods to an AIDS dataset, where viral load is censored by a lower detection limit. Simulation results confirm that the proposed models and methods offer substantial advantages over existing empirical covariate models for censored and mismeasured covariates.

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Immunologic Responses Associated with 12 Weeks of Combination Antiretroviral Therapy Consisting of Zidovudine, Lamivudine, and Ritonavir: Results of AIDS Clinical Trials Group Protocol 315

Cited by 397 publications

References 37 publications

Clinical forms and outcome of tuberculosis in HIV-infected patients in a tertiary hospital in São Paulo - Brazil

Clinical forms and outcome of tuberculosis in HIV-infected patients in a tertiary hospital in São Paulo - Brazil

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection

A mechanistic nonlinear model for censored and mismeasured covariates in longitudinal models, with application in AIDS studies

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