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Immunophenotypic alterations in acute and early HIV infection.

ABSTRACT: To understand the extent of immune dysregulation in primary HIV infection (PHI) and the impact of antiretroviral therapy (ART) on restoring these abnormalities, we longitudinally evaluated 52 subjects (Acute-Treated (AT); Early-Treated (ET); Early Untreated (EU)) for markers of activation, proliferation, and function on T cells. ET and AT patients differed by 0.54 log viral load (VL) at baseline but did not differ thereafter by more than 0.34 log10 VL. AT subjects had higher CD8(+) T cell counts and expression of markers indicative of CD8(+) T cell activation (CD38), and proliferation (Ki67), at baseline, than ET subjects but were not different 48 weeks post-ART. Although acute PHI is marked by higher level of immune activation than early PHI, virologic and immunologic responses were similar post-ART, suggesting that the extent of immunologic recovery is not negatively impacted by a delay of treatment beyond the acute stage of disease.

SUBMITTER: Al-Harthi L

PROVIDER: S-EPMC2702986 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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Immunophenotypic alterations in acute and early HIV infection.

Al-Harthi Lena L MaWhinney Sam S Connick Elizabeth E Schooley Robert T RT Forster Jeri E JE Benson Constance C Thompson Melanie M Judson Franklyn F Palella Frank F Landay Alan A

Clinical immunology (Orlando, Fla.) 20071003 3

To understand the extent of immune dysregulation in primary HIV infection (PHI) and the impact of antiretroviral therapy (ART) on restoring these abnormalities, we longitudinally evaluated 52 subjects (Acute-Treated (AT); Early-Treated (ET); Early Untreated (EU)) for markers of activation, proliferation, and function on T cells. ET and AT patients differed by 0.54 log viral load (VL) at baseline but did not differ thereafter by more than 0.34 log10 VL. AT subjects had higher CD8(+) T cell counts ...[more]

PMID: 17916441

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Project description:PurposeInitiation of combination antiretroviral therapy (cART) during acute or early HIV-infection (AEHI) limits the size of the viral reservoir and preserves immune function. This renders individuals who started cART during AEHI promising participants in HIV-cure trials. Therefore, we established a multicentre prospective cohort study in the Netherlands that enrols people with AEHI. In anticipation of future cure trials, we will longitudinally investigate the properties of the viral reservoir size and HIV-specific immune responses among cohort participants.ParticipantsParticipants immediately initiate intensified cART: dolutegravir, emtricitabine/tenofovir and darunavir/ritonavir (DRV/r). After 4 weeks, once baseline resistance data are available, DRV/r is discontinued. Three study groups are assembled based on the preparedness of individuals to participate in the extensiveness of sampling. Participants accepting immediate treatment and follow-up but declining additional sampling are included in study group 1 ('standard') and routine diagnostic procedures are performed. Participants willing to undergo blood, leukapheresis and semen sampling are included in study group 2 ('less invasive'). In study group 3 ('extended'), additional tissue (gut-associated lymphoid tissue, peripheral lymph node) and cerebrospinal fluid sampling are performed.Findings to dateBetween 2015 and 2020, 140 individuals with AEHI have been enrolled at nine study sites. At enrolment, median age was 36 (IQR 28-47) years, and 134 (95.7%) participants were men. Distribution of Fiebig stages was as follows: Fiebig I, 3 (2.1%); II, 20 (14.3%); III, 7 (5.0%); IV, 49 (35.0%); V, 39 (27.9%); VI, 22 (15.7%). Median plasma HIV RNA was 5.9 (IQR 4.7-6.7) log10 copies/mL and CD4 count 510 (IQR 370-700) cells/mm3. Median time from cART initiation to viral suppression was 8.0 (IQR 4.0-16.0) weeks.Future plansThe Netherlands Cohort Study on Acute HIV infection remains open for participant enrolment and for additional sites to join the network. This cohort provides a unique nationwide platform for conducting future in-depth virological, immunological, host genetic and interventional studies investigating HIV-cure strategies.

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Immunophenotypic alterations in acute and early HIV infection.

Publications

Immunophenotypic alterations in acute and early HIV infection.

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