Longitudinal assessment of immune response and viral characteristics in HIV-infected patients with prolonged CD4(+)/viral load discordance.
Although suppression of HIV-1 RNA below the limit of detection is associated with optimal outcomes, many patients can maintain or increase their CD4(+) count for prolonged time periods in the presence of persistent low-level viremia. We followed seven patients with prolonged (>5 years) discordant CD4(+)/viral load (VL) responses on protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) prospectively for 1 year to assess evolution of immune function, viral phenotype, replication capacity (RC), and resistance profile. Immune function was assessed by qualitative and quantitative measurement of cellular activation (CD38(+)HLA-DR(+) and CD38 antibodies bound per cell), and the interferon (IFN)-() ELISpot assay. Presence of syncytium-inducing (SI) or nonsyncytium-inducing (NSI) viral strains was determined by MT-2 cell culture. RC was measured by a modified rapid recombinant virus assay. The resistance profile was characterized by both genotypic and phenotypic analysis. Over the year of follow-up, IFN-() production to gag persisted, responses to other HIV antigens increased, and markers of cellular activation did not change. NSI virus predominated. The genotypic (GSS) and phenotypic (PSS) susceptibility scores remained stable. Evolution of RC was variable over the year of follow-up, but the RC of viruses remained well below that of wild-type clinical isolates. Thus, CD4(+)/VL discordance can be maintained for periods exceeding 5 years in some patients receiving PI-based HAART without significant evolution of HIV resistance.
Kaplan
Susan S
SS
Department of Medicine, Duke University Medical Center, Durham, NC 22710, USA.
Ferrari
Guido
G
Wrin
Terri
T
Hellmann
Nicholas S
NS
Tomaras
Georgia D
GD
Gryszowka
Victoria E
VE
Fiscus
Susan A
SA
Weinhold
Kent J
KJ
Hicks
Charles B
CB
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D010641:Phenotype; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D014779:Virus Replication
D011480:Protease Inhibitors; D012367:RNA, Viral