CD8+ cell anti-HIV activity rapidly increases upon discontinuation of early antiretroviral therapy.
BACKGROUND
CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course.


METHODS
In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment.


CONCLUSIONS
CD8+ lymphocytes from subjects with untreated primary HIV-1 infection strongly suppressed HIV replication. Initiation of antiretroviral therapy during primary HIV-1 infection caused a marked decline in this CNAR. CD8+ cells from these subjects regained anti-HIV activity when early therapy was discontinued. The timing of the appearance of CD8+ cell anti-HIV activity directly correlated with the emergence of detectable virus levels. Maximal CNAR activity coincided with a decay in the kinetics of HIV replication. In addition, peak viral loads during treatment interruption were lower than pre-treatment virus levels (median reduction = 0.8 logs, p = 0.005) and CD4+ T cell counts were maintained for a 24-week period of follow-up.


CONCLUSIONS
These results suggest that CNAR plays an important role in suppressing HIV replication in the setting of antiretroviral treatment interruption in HIV-infected individuals.
Killian
M Scott
MS
Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Roop
Jeremy
J
Ng
Sharon
S
Hecht
Frederick M
FM
Levy
Jay A
JA
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002452:Cell Count; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load; D014774:Virulence; D014779:Virus Replication / Q000187:drug effects
D015415:Biomarkers; D004279:DNA, Viral