Unexpected coreceptor usage of primary human immunodeficiency virus type 1 isolates from viremic patients under highly active antiretroviral therapy.
Recently, combinations of antiretroviral drugs (highly active antiretroviral therapy [HAART]) have led to a dramatic reduction of human immunodeficiency virus type 1 (HIV-1)-related clinical symptoms. Success of treatment is defined as almost complete suppression of plasma viremia, although in a sizable fraction of patients this goal is not achieved. We characterized primary HIV-1 isolates from 2 cohorts of patients in which HAART failed in terms of viral suppression. One cohort showed clinical benefit and stable or increasing CD4+ T cell numbers despite high viral load. The second viremic cohort had no CD4+ T cell recovery and exhibited typical AIDS-related symptoms. Primary isolates from HAART patients with minor clinical symptoms used CXCR4 as the most relevant receptor on primary cells. Thus, for the first time, it is shown that patients improving clinically under HAART harbor relatively high viral loads with viruses preferring CXCR4 as coreceptor.
Holtkamp
N
N
Paul-Ehrlich-Institut, Langen, Germany.
Otteken
A
A
Findhammer
S
S
Miller
V
V
Kurth
R
R
Werner
A
A
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000906:Antibodies / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000627:therapeutic use; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000821:virology
D019380:Anti-HIV Agents; D000906:Antibodies; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D015728:Receptors, HIV