Treatment intensification has no effect on the HIV-1 central nervous system infection in patients on suppressive antiretroviral therapy.
BACKGROUND
Antiretroviral treatment (ART) significantly reduces cerebrospinal fluid (CSF) HIV-1 RNA levels and residual viremia is less frequently found in CSF than in blood. However, persistent intrathecal immunoactivation is common, even after several years of ART. To investigate whether low-level CSF viremia and residual immunoactivation within the central nervous system (CNS) derive from ongoing local viral replication, we conducted a study of treatment intensification in patients on effective ART.


METHODS
Ten patients on ART with plasma HIV RNA <50 copies per milliliter for >18 months were included. Intensification was given for in total 8 weeks: 4 weeks with maraviroc or lopinavir/ritonavir (good CNS penetration), and 4 weeks with enfuvirtide (poor CNS penetration). Lumbar punctures were performed 4 weeks before, at intensification commencement, at switchover after 4 weeks, at the conclusion of, and 4 weeks after the intensification period.


RESULTS
No significant changes in HIV RNA, neopterin, β2-microglobulin, immunoglobulin G index, albumin ratio, and CD4(+) T-cell count were observed, either in CSF or blood, neither before, during, nor after the intensification periods.


CONCLUSIONS
ART intensification did not reduce residual CSF HIV RNA levels or intrathecal immunoactivation in patients on ART. These findings do not support an ongoing viral replication in CNS.
Yilmaz
Aylin
A
Department of Infectious Diseases, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Verhofstede
Chris
C
D'Avolio
Antonio
A
Watson
Victoria
V
Hagberg
Lars
L
Fuchs
Dietmar
D
Svennerholm
Bo
B
Gisslén
Magnus
M
D000328:Adult; D000418:Albumins / Q000134:cerebrospinal fluid; D019380:Anti-HIV Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002494:Central Nervous System Infections / Q000188:drug therapy* / Q000821:virology*; D018592:Cross-Over Studies; D003510:Cyclohexanes / Q000627:therapeutic use; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D061466:Lopinavir / Q000627:therapeutic use; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D019798:Neopterin / Q000097:blood / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D019438:Ritonavir / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication
D000418:Albumins; D019380:Anti-HIV Agents; D003510:Cyclohexanes; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D010446:Peptide Fragments; D012367:RNA, Viral; D014230:Triazoles; D000077560:Enfuvirtide; D061466:Lopinavir; D019798:Neopterin; D000077592:Maraviroc; D019438:Ritonavir