HIV DNA levels predictive of disease progression, could provide cheaper viral load test

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Measuring levels of HIV DNA may be a useful tool for assessing the chances of HIV disease progression, particularly in resource-limited settings, according to a US study published online in the January 1st 2003 edition of the Journal of Infectious Diseases.

Investigators recruited 111 eligible patients from the AIDS Clinical Trials Group (ACTG) Study 175, which looked at the safety and efficacy of nucleoside analogues when given as either monotherapy or dual therapy. All patients in the study had a CD4 count at baseline of between 200 and 500/mm3. The study looked at the prognostic values of HIV RNA levels (the now routine HIV viral load test); CD4 count; infectious HIV titer; and HIV DNA levels. The infectious titer and HIV DNA tests were measured by examining peripheral blood mononuclear cells.

Tests to measure each of the above were performed at baseline and then at eight, 20 and 56 weeks. The study had three possible end points: the ACTG 175 end point (a 50% fall in CD4 count, development of an AIDS defining illness or death); death from AIDS or another cause; or survival.

Glossary

deoxyribonucleic acid (DNA)

The material in the nucleus of a cell where genetic information is stored.

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.

 

prognosis

The prospect of survival and/or recovery from a disease as anticipated from the usual course of that disease or indicated by the characteristics of the patient.

disease progression

The worsening of a disease.

reservoir

The ‘HIV reservoir’ is a group of cells that are infected with HIV but have not produced new HIV (latent stage of infection) for many months or years. Latent HIV reservoirs are established during the earliest stage of HIV infection. Although antiretroviral therapy can reduce the level of HIV in the blood to an undetectable level, latent reservoirs of HIV continue to survive (a phenomenon called residual inflammation). Latently infected cells may be reawakened to begin actively reproducing HIV virions if antiretroviral therapy is stopped. 

At baseline, having symptomatic HIV disease and being white were found to be significantly associated with higher HIV DNA levels. Baseline HIV RNA levels and infectious titer were also significantly associated with HIV DNA. This was also the case at all three follow-up intervals.

In both univariate and multivariate analysis, higher HIV DNA levels were associated with a trend towards faster disease progression, whilst lower HIV DNA was found to be associated with a trend towards slower emergence of symptoms of HIV illness and death.

The investigators noted that with only 111 patients their study was small, “but that the data suggest an association between higher baseline HIV-1 DNA with reduced survival time and warrants further investigation. This association is supported by the observed relationship of increased values of quantitative HIV-1 DNA with symptomatic HIV disease status at study entry.”

Infectious titer was not found to have any prognostic value by the investigators, and no strong association was found between HIV DNA levels and CD4 count. The investigators speculate that HIV DNA levels may be indicative of “total body burden of HIV, including the latent reservoir of HIV-1 integrated into” CD4 memory cells, adding that these tests may be particularly useful as HIV RNA viral load only reflects recent viral replication which reduces dramatically with antiretroviral therapy.

The investigators conclude that levels of HIV DNA are associated with other indicators of disease progression and that “the total magnitude of the reservoir of HIV may be associated with survival.”

They suggest that measurement of HIV-1 DNA from dried blood spots or frozen samples may provide an assay that is a more robust alternative to HIV-1 RNA, enabling its use in resource-limited settings.

A Thai study, conducted in collaboration with the US Centers for Disease Control, presented at the XIV International AIDS Conference in Barcelona earlier this year, found that dried blood spots were a reliable means of testing HIV-1 DNA (Young 2002).

Further information on this website

The immune system and HIV

Medical tests – predicting prognosis with viral load

Medical tests – predicting prognosis with CD4 counts

Prognosis Factsheet

Monitoring where resources are limited.

References

Tierney C et al Prognostic value of baseline human immunodeficiency type 1 DNA measurement for disease progression in patients receiving nucleoside analogues Journal of Infectious Diseases 187:144-148, 2002.

Young NL et al. Use of dried blood spots for diagnosis and viral quantification

in perinatal HIV-1 infection in Thailand. XIV International AIDS Conference, Barcelona, abstract WeOrB1339, 2002.