Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection.
Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection.
Altfeld
M
M
Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA.
Rosenberg
E S
ES
Shankarappa
R
R
Mukherjee
J S
JS
Hecht
F M
FM
Eldridge
R L
RL
Addo
M M
MM
Poon
S H
SH
Phillips
M N
MN
Robbins
G K
GK
Sax
P E
PE
Boswell
S
S
Kahn
J O
JO
Brander
C
C
Goulder
P J
PJ
Levy
J A
JA
Mullins
J I
JI
Walker
B D
BD
D000208:Acute Disease; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006679:HIV Seropositivity / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular; D008137:Longitudinal Studies; D008297:Male; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors
D017931:DNA Primers; D000939:Epitopes; D012367:RNA, Viral