Quantitation of human immunodeficiency virus type 1 DNA forms with the second template switch in peripheral blood cells predicts disease progression independently of plasma RNA load
Date
2002Author
![ORCID logo](https://orcid.org/sites/default/files/images/orcid_16x16.png)
Touloumi, G.
Karanicolas, R.
Pantazis, N.
Anastassopoulou, C. G.
Karafoulidou, A.
Goedert, J. J.
Hatzakis, Angelos E.
ISSN
0022-538XSource
Journal of virologyVolume
76Pages
10099-10108Google Scholar check
Keyword(s):
Metadata
Show full item recordAbstract
There are several forms of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood T cells and lymph nodes in untreated HIV-1-infected individuals and in patients whose plasma HIV-1 RNA levels are suppressed by long-term combination antiretroviral therapy. However, it remains to be established whether the concentration of HIV-1 DNA in cells predicts the clinical outcome of HIV-1 infection. In this report, we measured the concentration of HIV-1 DNA forms which has undergone the second template switch (STS DNA) and 2-long-terminal-repeat DNA circles in peripheral blood mononuclear cell (PBMC) samples. To do this, we used molecular-beacon-based real-time PCR assays and studied 130 patients with hemophilia in the Multi-center Hemophilia Cohort Study. We assessed the influence of baseline HIV-1 STS DNA levels on the progression of HIV-1 disease in the absence of combination antiretroviral therapy by Kaplan-Meier and Cox regression analysis. Among the patients who progressed to AIDS, the median levels (interquartile ranges) of STS HIV-1 DNA in PBMC were significantly higher than those of patients who remained AIDS free during the 16 years of follow-up (1,017 [235 to 6,059] and 286 [31 to 732] copies per 106 PBMC, respectively P < 0.0001). Rates of progression to death and development of AIDS varied significantly (log rank P < 0.001) by quartile distribution of HIV-1 STS DNA levels. After adjustment for age at seroconversion, baseline CD4+ T-cell counts, plasma viral load, and T-cell-receptor excision circles, the relative hazards (RH) of death and AIDS were significantly increased with higher HIV-1 STS DNA levels (adjusted RH, 1.84 [95% confidence interval {CI}, 1.30 to 2.59] and 2.62 [95% CI, 1.75 to 3.93] per 10-fold increase per 106 PBMC, respectively). HIV-1 STS DNA levels in each individual remained steady in longitudinal PBMC samples during 16 years of follow-up. Our findings show that the concentration of HIV-1 STS DNA in PBMC complements the HIV-1 RNA load in plasma in predicting the clinical outcome of HIV-1 disease. This parameter may have important implications for understanding the virological response to combination antiretroviral therapy.
Collections
Cite as
Related items
Showing items related by title, author, creator and subject.
-
Article
Viral correlates of HIV-1 disease
Anastassopoulou, C. G.; Kostrikis, Leontios G. (2005)The transmission of HIV and the progression of HIV disease are influenced not only by a large number of human host factors, but also by certain correlates of the ever fluctuating virus quasispecies. The present review ...
-
Article
Shared mechanisms in stemness and carcinogenesis: Lessons from oncogenic viruses
Iacovides, D.; Michael, S.; Achilleos, Charis; Strati, Katerina (2013)A rise in technologies for epigenetic reprogramming of cells to pluripotency, highlights the potential of understanding and manipulating cellular plasticity in unprecedented ways. Increasing evidence points to shared ...
-
Article
Re-analysis of human immunodeficiency virus type 1 isolates from Cyprus and Greece, initially designated 'subtype I', reveals a unique complex A/G/H/K/? mosaic pattern
Paraskevis, Dimitrios N.; Magiorkinis, M.; Vandamme, A. M.; Kostrikis, Leontios G.; Hatzakis, Angelos E. (2001)Human immunodeficiency virus type 1 (HIV-1) has been classified into three main groups and 11 distinct subtypes. Moreover, several circulating recombinant forms (CRFs) of HIV-1 have been recently documented to have spread ...