Neutralization profiles of sera from human immunodeficiency virus (HIV)-infected individuals: relationship to HIV viral load and CD4 cell count.
The relationship of the neutralizing activity (NA) profile of sera from human immunodeficiency virus (HIV)-infected individuals to the HIV viral load and the absolute CD4 count was examined. The NA of 24 serum samples against autologous isolates (AI) and HIV type 1 strain MN was examined. Three NA patterns were recognized. Nine sera neutralized both AI and MN (+/+), six sera neutralized MN but not AI (-/+), and nine sera failed to neutralize both AI and MN (-/-). The identification of the three neutralization patterns (+/+, -/+, and -/-) indicated that resistance to neutralization was progressive. A reciprocal relationship between the viral burden of the patients and the NA profiles was observed. The nine subjects with a -/- NA profile had a plasma viral load of > or =5 x 10(4) copies/ml and a cellular viral burden of > or =1,122 infectious units per million viable cells, which were significantly different from those of the other groups (P < 0.02). These patterns were independent of the phenotypic characteristics of the virus. Longitudinally, subjects with a -/- profile at baseline gained their HIV-specific NA by 24 weeks of antiretroviral therapy when this was associated with a >/=1-log(10) decline in the plasma HIV viral load. The sera from week 24 from some patients were able to neutralize both the 24-week and the baseline dominant virus isolates. A change in CD4 cell count of 50 or more in either direction predicted a -/- or +/+ profile. The verification of the autologous NA profile might be important in selecting patients who may benefit from immune-based therapies involving neutralizing monoclonal antibodies.
Nokta
M
M
Department of Internal Medicine, Division of Infectious Disease, University of Texas Medical Branch, Galveston, TX 77555-0835, USA. mnokta@utmb.edu
Turk
P
P
Loesch
K
K
Pollard
R B
RB
D000163:Acquired Immunodeficiency Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000097:blood; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D006678:HIV / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000032:analysis*; D006801:Humans; D016756:Immunoglobulins, Intravenous; D016130:Immunophenotyping; D008297:Male; D009154:Mutation; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood; D013045:Species Specificity; D019562:Viral Load; D014766:Viremia / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology
D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D015415:Biomarkers; D015488:HIV Antigens; D016756:Immunoglobulins, Intravenous; D012367:RNA, Viral