Plasma viral load and CD4+ lymphocytes as prognostic of HIV-1 infection
ABSTRACT The rate of disease progression among persons infected with human immunodeficiency virus type 1 (HIV-1) varies widely, and the relative prognostic value of markers of disease activity has not been defined.
To compare clinical, serologic, cellular, and virologic markers for their ability to predict progression to the acquired immunodeficiency syndrome (AIDS) and death during a 10-year period.
Prospective, multicenter cohort study.
Four university-based clinical centers participating in the Multicenter AIDS Cohort Study.
1604 men infected with HIV-1.
The markers compared were oral candidiasis (thrush) or fever; serum neopterin levels; serum beta 2-microglobulin levels; number and percentage of CD3+, CD4+, and CD8+ lymphocytes; and plasma viral load, which was measured as the concentration of HIV-1 RNA found using a sensitive branched-DNA signal-amplification assay.
Plasma viral load was the single best predictor of progression to AIDS and death, followed (in order of predictive strength) by CD4+ lymphocyte count and serum neopterin levels, serum beta 2-microglobulin levels, and thrush or fever. Plasma viral load discriminated risk at all levels of CD4+ lymphocyte counts and predicted their subsequent rate of decline. Five risk categories were defined by plasma HIV-1 RNA concentrations: 500 copies/mL or less, 501 to 3000 copies/mL, 3001 to 10000 copies/mL, 10001 to 30000 copies/mL, and more than 30000 copies/mL. Highly significant (P < 0.001) differences in the percentages of participants who progressed to AIDS within 6 years were seen in the five risk categories: 5.4%, 16.6%, 31.7%, 55.2%, and 80.0%, respectively. Highly significant (P < 0.001) differences in the percentages of participants who died of AIDS within 6 years were also seen in the five risk categories: 0.9%, 6.3%, 18.1%, 34.9%, and 69.5%, respectively. A regression tree incorporating both HIV-1 RNA measurements and CD4+ lymphocyte counts provided better discrimination of outcome than did either marker alone; use of both variables defined categories of risk for AIDS within 6 years that ranged from less than 2% to 98%.
Plasma viral load strongly predicts the rate of decrease in CD4+ lymphocyte count and progression to AIDS and death, but the prognosis of HIV-infected persons is more accurately defined by combined measurement of plasma HIV-1 RNA and CD4+ lymphocytes.
- SourceAvailable from: Uwe Fiebig
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- "As well as leukaemia, GaLV, MuLV, and FeLV induce immunodeficiency in their respective hosts, leaving them susceptible to numerous opportunistic infections (Moloney, 1964; Rosenberg and Jolicoeur, 1997; Hardy, 1993; Gallo et al., 1978; Kannian and Green, 2010). As is the case with virus loads and AIDS in HIV-1 infected humans, there is a correlation between KoRV RNA levels in the plasma and neoplastic disease in koalas (Tarlinton et al., 2005; Mellors et al., 1997). KoRVs are likely the result of a relatively recent trans-species transmission from rodents or bats (see Denner and Young, 2013). "
ABSTRACT: Many wild koalas are infected with the koala retrovirus, KoRV, some of which suffer from lymphoma and chlamydial disease. Three subgroups, KoRV-A, KoRV-B and KoRV-J, have so far been described. It is well known that other closely related gammaretroviruses can induce tumours and severe immunodeficiencies in their respective hosts and a possible role for KoRV infection in lymphoma and chlamydial disease in koalas has been suggested. In many wild koalas, KoRV-A has become endogenised, i.e., it is integrated in the germ-line and is passed on with normal cellular genes. In this study, sera from koalas in European zoos and from wild animals in Australia were screened for antibodies against KoRV-A. These naturally infected animals all carry endogenous KoRV-A and two zoo animals are also infected with KoRV-B. The antibody response is generally an important diagnostic tool for detecting retrovirus infections. However, when Western blot analyses were performed using purified virus or recombinant proteins corresponding to KoRV-A, none of the koalas tested positive for specific antibodies, suggesting a state of tolerance. These results have implications for koala vaccination, as they suggest that therapeutic immunisation of animals carrying and expressing endogenous KoRV-A will not be successful. However, it remains unclear whether these animals can be immunised against KoRV-B and immunisation of uninfected koalas could still be worthwhile. Copyright © 2015. Published by Elsevier B.V.Virus Research 01/2015; 198. DOI:10.1016/j.virusres.2015.01.002 · 2.83 Impact Factor
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Dataset: CD4+ T Lymphocyte
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- "Currently, more than 10 million individuals receiving HIV-1 antiretroviral therapy, many of which living in low- and middle-income countries . HIV-1 viral quantitation is essential for treatment monitoring –. "
ABSTRACT: HIV-1 viral quantitation is essential for treatment monitoring. An in-house assay would decrease financial barriers to access. A real-time competitive RT-PCR in house assay (Sing-IH) was developed in Singapore. Using HXB2 as reference, the assay's primers and probes were designed to generate a 183-bp product that overlaps a portion of the LTR region and gag region. A competitive internal control (IC) was included in each assay to monitor false negative results due to inhibition or human error. Clinical evaluation was performed on 249 HIV-1 positive patient samples in comparison with the commercially available Generic HIV Viral Load assay. Correlation and agreement of results were assessed for plasma HIV-1 quantification with both assays. The assay has a lower limit of detection equivalent to 126 copies/mL of HIV-1 RNA and a linear range of detection from 100-1000000 copies/mL. Comparative analysis with reference to the Generic assay demonstrated good agreement between both assays with a mean difference of 0.22 log10 copies/mL and 98.8% of values within 1 log10 copies/mL range. Furthermore, the Sing-IH assay can quantify HIV-1 group M subtypes A-H and group N isolates adequately, making it highly suitable for our region, where subtype B and CRF01_AE predominate. With a significantly lower running cost compared to commercially available assays, the broadly sensitive Sing-IH assay could help to overcome the cost barriers and serve as a useful addition to the currently limited HIV viral load assay options for resource-limited settings.PLoS ONE 03/2014; 9(3):e89826. DOI:10.1371/journal.pone.0089826 · 3.23 Impact Factor