TTV viral load as a marker for immune reconstitution after initiation of HAART in HIV-infected patients.
OBJECTIVE
To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART).


METHODS
Fifteen protease inhibitor-naïve HIV-infected patients were included in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples taken during HAART were analyzed. TTV was detected by polymerase chain reaction (PCR) and was quantitated by competitive PCR. TTV viral heterogeneity was determined by restriction fragment length polymorphisms (RFLPs) and sequencing.


RESULTS
All 15 HIV-infected patients were TTV positive. No significant change in HIV RNA or TTV viral load was observed at the three time points before HAART initiation. Even though HAART lead to an immediate and significant reduction in HIV RNA (p =.0001), a significant reduction in TTV viral load (p =.0002) was not observed until after 3-5 months of HAART. Four patients did not have an increase in CD4+ T cell count after 1 year of HAART; however, a decrease in TTV viral load was still observed, and three of these patients had a reduction in HIV RNA. RFLPs and sequencing revealed that TTV is represented as a heterogeneous population of virus in HIV-infected patients.


CONCLUSIONS
This pilot study suggests that HAART leads to improved immunological responses, even in patients who do not have an increase in CD4+ T cell counts. We propose that the change in TTV viral load may be useful in the evaluation of cellular immune response at a functional level in HIV-infected patients who receive HAART.
Clinical Research Unit, Copenhagen University Hospital, Hvidovre, Denmark.
Chris D
CD
Madsen
Jesper
J
Eugen-Olsen
Ole
O
Kirk
Jan
J
Parner
Jens
J
Kaae Christensen
Marie S
MS
Brasholt
Jens
J
Ole Nielsen
Kim
K
Krogsgaard
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D012367:RNA, Viral / Q000032:analysis; D022783:Torque teno virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019562:Viral Load
D015415:Biomarkers; D004279:DNA, Viral; D012367:RNA, Viral