HIV-1-specific CD4+ T cell responses in chronically HIV-1 infected blippers on antiretroviral therapy in relation to viral replication following treatment interruption.
The impact of transient viral load blips on anti-HIV-1 immune responses and on HIV-1 rebound following treatment interruption (TI) is not known. Clinical and immunological parameters were measured during 40 weeks of antiretroviral therapy (ART) and following TI in an observational cohort of 16 chronically HIV-1-infected subjects with or without observed viral load blips during ART. During therapy, blips in seven subjects were associated with higher anti-HIV-1 (p24) CD4+ T cell lymphoproliferative responses (p = 0.04), without a significant difference in T cell activation or total anti-HIV-1 CD8+ T cell interferon-gamma (IFN-gamma) responses when compared to nine matched non-blippers. Therapy interruption resulted in a significantly higher viral rebound in blippers by 8 week despite retention of higher lymphoproliferative p24 responses (p = 0.01) and a rise in CD3+ T cell activation (p = 0.04) and anti-HIV-1 CD8+ T cell responses in blippers by week 4 when compared to non-blippers. Past week 4 of interruption, therapy re-initiation criteria were also met by a higher frequency in blippers by week 14 (p < 0.04) with no difference between groups by week 24. These data support that blippers have higher anti-HIV lymphoproliferative responses while on ART but experience equal to higher viral rebound as compared to matched non-blippers upon TI.
Papasavvas
Emmanouil
E
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA. montaner@wistar.org
Kostman
Jay R
JR
Thiel
Brian
B
Pistilli
Maxwell
M
Mackiewicz
Agnieszka
A
Foulkes
Andrea
A
Gross
Robert
R
Jordan
Kimberly A
KA
Nixon
Douglas F
DF
Grant
Robert
R
Poulin
Jean-Francois
JF
McCune
Joseph M
JM
Mounzer
Karam
K
Montaner
Luis J
LJ
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication
D019380:Anti-HIV Agents; D012367:RNA, Viral