Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control.
Mechanisms that underly discordant CD4+ cell/virus load (VL) responses in patients who receive highly active antiretroviral therapy (HAART) were studied in 30 human immunodeficiency virus (HIV)-positive patients, in 3 groups. Discordant responders maintained CD4+ cell levels >200/mm(3) with stable or increasing trend, despite sustained VLs of 500-5000 copies/mL, for >2 years. Treatment-success patients had CD4+ cell counts >200/mm(3) with stable or increasing trend and VLs <50 copies/mL, for >2 years. Treatment-failure patients initially responded to HAART, followed by decreasing CD4+ cell counts and increasing VLs. Interferon-gamma production to gag and noncytolytic CD8+ cell suppressive activity were greater in discordant responders. Cellular activation was greatest in patients with treatment failure. All discordant responders had non-syncytium-inducing (CCR5-tropic) viruses. Viruses from discordant responders and from patients with treatment failure had extensive resistance mutations; discordant responders had significantly lower viral replication capacities. These findings suggest that discordant responses may be related to enhanced HIV-directed immune responses, diminished cellular activation, decreased viral replication capacity, and preservation of non-syncytium-inducing virus strains.
Sufka
Susan A
SA
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Ferrari
Guido
G
Gryszowka
Victoria E
VE
Wrin
Terri
T
Fiscus
Susan A
SA
Tomaras
Georgia D
GD
Staats
Herman F
HF
Patel
Dhavalkumar D
DD
Sempowski
Gregory D
GD
Hellmann
Nicholas S
NS
Weinhold
Kent J
KJ
Hicks
Charles B
CB
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D017320:HIV Protease Inhibitors