Recovery of Replication‐Competent Virus from CD4 T Cell Reservoirs and Change in Coreceptor Use in Human Immunodeficiency Virus Type 1–Infected Children Responding to Highly Active Antiretroviral Therapy

Equils, Ozlem; Garratty, Eileen; Wei, Lian S.; Plaeger, Susan; Tapia, Millie; Deville, Jaime G.; Krogstad, Paul; Sim, Myung‐Shin; Nielsen, Karin; Bryson, Yvonne J.

doi:10.1086/315758

Cited by 32 publications

(22 citation statements)

References 37 publications

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“…A recent study of HIV-1-infected children showed that HAART was associated with a restriction in the number of coreceptors used. Although most of the children did not have X4-using virus strains before treatment, a shift in coreceptor usage from X4 to R5 was seen in a few children who had a response to HAART (28).…”

Section: Discussionmentioning

confidence: 95%

Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy

et al. 2001

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Section: Discussionmentioning

confidence: 95%

Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy

et al. 2001

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“…As reported here and previously (31), X4 viruses are not more susceptible to PRO 542 in vitro. However, selective loss of X4 viruses has also been reported following conventional antiretroviral therapy (9,26,30) and may reflect a higher turnover rate of cells infected by X4 viruses. PRO 542 therapy did not lead to emergence of X4 viruses in any of the patients studied.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Advanced Human Immunodeficiency Virus Type 1 Disease with the Viral Entry Inhibitor PRO 542

Jacobson

Israel

Lowy

et al. 2004

Antimicrob Agents Chemother

117

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Viral entry inhibitors represent an emerging mode of therapy for human immunodeficiency virus type 1 (HIV-1) infection. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4 ؉ cells. Previously, PRO 542 demonstrated antiviral activity without significant toxicity when tested at single doses ranging to 10 mg/kg. In this study, 12 HIV-infected individuals were treated with 25-mg/kg single-dose PRO 542 and then monitored for safety, antiviral effects, and PRO 542 pharmacokinetics for 6 weeks. The study examined two treatment cohorts that differed in the extent of HIV-1 disease progression. PRO 542 at 25 mg/kg was well tolerated and demonstrated a serum half-life of 3 days. Statistically significant acute reductions in HIV-1 RNA levels were observed across all study patients, and greater antiviral effects were observed in the cohort of patients with more advanced HIV-1 disease. In advanced disease (HIV-1 RNA > 100,000 copies/ml; CD4 lymphocytes < 200 cells/mm 3 ), PRO 542 mediated an 80% response rate and statistically significant Ϸ0.5 log 10 mean reductions in viral load for 4 to 6 weeks posttreatment. Similar findings were obtained in an analysis of all (n ‫؍‬ 11) advanced disease patients treated to date with single doses of PRO 542 ranging from 1 to 25 mg/kg. In addition, a significant correlation was observed between antiviral effects observed in vivo and viral susceptibility to PRO 542 in vitro. The findings support continued development of PRO 542 for salvage therapy of advanced HIV-1 disease.

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“…HAART may impact HIV, despite incomplete suppression of viral replication, either by resulting in changes in the tropism [6,34] or fitness of the virus [35,36]. SI variants of HIV-1 [26], T cell tropic viruses that use CX chemokine receptor 4 as a coreceptor for entry into CD4 cells [37], are associated with accelerated T cell decline and rapid disease progression [38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Immunoreconstitution in Children Receiving Highly Active Antiretroviral Therapy Depends on the CD4 Cell Percentage at Baseline

Nikolic-Djokic¹,

Essajee²,

Rigaud³

et al. 2002

J INFECT DIS

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The effect of highly active antiretroviral therapy (HAART) in 85 children infected with human immunodeficiency virus type 1 (HIV-1) was compared retrospectively among Centers for Disease Control and Prevention (CDC) immunologic groups 1-3. The duration of HAART did not vary significantly among the immunologic groups (median, 39.07 months). The CD4 cell percentage increased in 39.1%, 58.3%, and 90% of patients in CDC groups 1-3, respectively (P <.001). HAART resulted in the suppression of HIV-1 below detectable levels in 34.8%, 25%, and 32% of patients in the 3 CDC groups, respectively, and in a frequent switch from syncytium-inducing to nonsyncytium-inducing virus. Thymic excision circles increased in a subset of patients with increases in CD4 cell percentage independently of HIV RNA level. The results support the option of delaying HAART in early asymptomatic HIV-1 disease in children and the use of other markers of disease progression, in addition to virus load.

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Recovery of Replication‐Competent Virus from CD4 T Cell Reservoirs and Change in Coreceptor Use in Human Immunodeficiency Virus Type 1–Infected Children Responding to Highly Active Antiretroviral Therapy

Cited by 32 publications

References 37 publications

Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy

Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy

Treatment of Advanced Human Immunodeficiency Virus Type 1 Disease with the Viral Entry Inhibitor PRO 542

Immunoreconstitution in Children Receiving Highly Active Antiretroviral Therapy Depends on the CD4 Cell Percentage at Baseline

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