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Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy.
J Infect Dis 2005; 191(3):348-57JI

Abstract

BACKGROUND

Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined.

METHODS

For 24 months, 101 HAART-treated, HIV-1-infected patients with HIV RNA levels </=200 copies/mL were followed prospectively: HIV RNA level and CD4 and CD8 cell counts were investigated every 3 months, and proviral DNA and T cell subsets were investigated every 6 months.

RESULTS

During follow-up, 33 patients had HIV RNA levels </=20 copies/mL at all visits (uVL patients), whereas 68 patients had HIV RNA levels >20 copies/mL at >/=1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37-480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients (P<.05). A higher HIV RNA level was independently associated with reduced CD4 gain (P<.001). A higher HIV RNA level also was associated with increases in activated CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells (P<.05), and a higher level of activated CD8(+)CD38(+) cells was independently associated with reduced CD4 gain (P<.05). A higher proviral DNA level was associated with increases in CD4(+)CD45RA(-)CD28(-) effector cells and reductions in naive CD4(+)CD45RA(+)CD62L(+) and CD8(+)CD45RA(+)CD62L(+) cells (P<.05). Higher levels of activated CD4(+)HLA-DR(+) and early differentiated CD4(+)CD45RA(-)CD28(+) cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA (P<.05).

CONCLUSION

These findings indicate that low-level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART.

Authors+Show Affiliations

Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. sro@dadlnet.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15633093

Citation

Ostrowski, Sisse R., et al. "Low-level Viremia and Proviral DNA Impede Immune Reconstitution in HIV-1-infected Patients Receiving Highly Active Antiretroviral Therapy." The Journal of Infectious Diseases, vol. 191, no. 3, 2005, pp. 348-57.
Ostrowski SR, Katzenstein TL, Thim PT, et al. Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy. J Infect Dis. 2005;191(3):348-57.
Ostrowski, S. R., Katzenstein, T. L., Thim, P. T., Pedersen, B. K., Gerstoft, J., & Ullum, H. (2005). Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy. The Journal of Infectious Diseases, 191(3), pp. 348-57.
Ostrowski SR, et al. Low-level Viremia and Proviral DNA Impede Immune Reconstitution in HIV-1-infected Patients Receiving Highly Active Antiretroviral Therapy. J Infect Dis. 2005 Feb 1;191(3):348-57. PubMed PMID: 15633093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy. AU - Ostrowski,Sisse R, AU - Katzenstein,Terese L, AU - Thim,Per T, AU - Pedersen,Bente K, AU - Gerstoft,Jan, AU - Ullum,Henrik, Y1 - 2004/12/30/ PY - 2004/04/25/received PY - 2004/07/08/accepted PY - 2005/1/6/pubmed PY - 2005/2/18/medline PY - 2005/1/6/entrez SP - 348 EP - 57 JF - The Journal of infectious diseases JO - J. Infect. Dis. VL - 191 IS - 3 N2 - BACKGROUND: Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined. METHODS: For 24 months, 101 HAART-treated, HIV-1-infected patients with HIV RNA levels </=200 copies/mL were followed prospectively: HIV RNA level and CD4 and CD8 cell counts were investigated every 3 months, and proviral DNA and T cell subsets were investigated every 6 months. RESULTS: During follow-up, 33 patients had HIV RNA levels </=20 copies/mL at all visits (uVL patients), whereas 68 patients had HIV RNA levels >20 copies/mL at >/=1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37-480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients (P<.05). A higher HIV RNA level was independently associated with reduced CD4 gain (P<.001). A higher HIV RNA level also was associated with increases in activated CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells (P<.05), and a higher level of activated CD8(+)CD38(+) cells was independently associated with reduced CD4 gain (P<.05). A higher proviral DNA level was associated with increases in CD4(+)CD45RA(-)CD28(-) effector cells and reductions in naive CD4(+)CD45RA(+)CD62L(+) and CD8(+)CD45RA(+)CD62L(+) cells (P<.05). Higher levels of activated CD4(+)HLA-DR(+) and early differentiated CD4(+)CD45RA(-)CD28(+) cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA (P<.05). CONCLUSION: These findings indicate that low-level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/15633093/Low_level_viremia_and_proviral_DNA_impede_immune_reconstitution_in_HIV_1_infected_patients_receiving_highly_active_antiretroviral_therapy_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/427340 DB - PRIME DP - Unbound Medicine ER -