Immune escape mutations detected within HIV-1 epitopes associated with viral control during treatment interruption.
We analyzed immune responses in chronically HIV-infected individuals who took part in a treatment interruption (TI) trial designed for patients who initiated antiretroviral therapy within 6 months of seroconversion. In the 2 subjects who exhibited the best viral control, we detected CD8(+) T-cell responses against 1-2 Gag epitopes during the early weeks of TI and a subsequent increase in the number of epitopes recognized by the later time points. Each of these subjects developed mutations within the epitopes targeted by the highest magnitude responses. In the subject with the worst viral control, we detected responses against 2 Gag epitopes throughout the entire TI and no Gag mutations. The magnitude of these responses increased dramatically with time, greatly exceeding those detected in the virologic controllers. The highest levels of contemporaneous autologous neutralizing antibody activity were detected in the virologic controllers, and a subsequent escape mutation developed within the envelope gene of one controller that abrogated the response. These data suggest that immune escape mutations are a sign of viral control during TI, and that the absence of immune escape mutations in the presence of high levels of viral replication indicates the lack of an effective host immune response.
Schweighardt
Becky
B
Monogram Biosciences, Inc, 345 Oyster Point Boulevard, South San Francisco, CA 94080, USA. bschweighardt@monogrambio.com
Wrin
Terri
T
Meiklejohn
Duncan A
DA
Spotts
Gerald
G
Petropoulos
Christos J
CJ
Nixon
Douglas F
DF
Hecht
Frederick M
FM
D057134:Antibodies, Neutralizing / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008137:Longitudinal Studies; D009154:Mutation; D009500:Neutralization Tests; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics / Q000276:immunology; D028761:Withholding Treatment; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D057134:Antibodies, Neutralizing; D000939:Epitopes; D019302:HIV Envelope Protein gp160; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma