Older age associated with bigger increases in viral load and falls in CD4 count in patients not taking HIV treatment

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Results of a large observational study underline the importance of closely monitoring viral load in HIV-positive patients who have yet to start antiretroviral therapy, especially if they are older. The research is published ahead of print in the online edition of AIDS. Viral load increased progressively with time, and increases were especially sharp in older patients. Falls in CD4 cell count were closely related to current viral load.

“The current viral load, to a much greater degree than any previous measure, determines the ongoing rate of CD4 count depletion,” comment the authors. “Age was significantly associated with the change in viral load. Faster rises were observed in older people.”

In people who are antiretroviral naive (have not started HIV treatment), HIV infection usually involves a steady increase in viral load accompanied by a fall in CD4 cell count. If HIV therapy is not started, this leads to the development of opportunistic infections and AIDS-related death.



In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

drug interaction

A risky combination of drugs, when drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.


A person who has never taken treatment for a condition.

opportunistic infection (OI)

An infection that occurs more frequently or is more severe in people with weakened immune systems, such as people with low CD4 counts, than in people with healthy immune systems. Opportunistic infections common in people with advanced HIV disease include Pneumocystis jiroveci pneumonia; Kaposi sarcoma; cryptosporidiosis; histoplasmosis; other parasitic, viral, and fungal infections; and some types of cancer. 

Routine HIV care should therefore involve the regular monitoring of CD4 count and viral load. However, there are ongoing uncertainties about the precise rate of viral load increase in treatment-naive individuals and the relationship with falls in CD4 count. It is also unclear if co-factors such as age, sex and HIV transmission category are associated with faster changes in these key prognostic markers.

A clearer understanding of these important questions is needed to better inform decisions about the best time to start HIV treatment. Investigators from a collaboration of 36 European cohort studies (COHERE) therefore analysed paired CD4 and viral load measures from 34,384 antiretroviral-naive adult patients who received care between 1984 and 2011.

The patients contributed total of 158,385 paired measurements. The median age at baseline was 34 years. Approximately three-quarters (73%) of participants were men, 34% were white and 12% acquired HIV via injecting drug use. Median CD4 count and viral load at baseline were 477 cells/mm3 and 10,000 copies/ml, respectively.

Viral load increased by a mean of 0.091 log10/copies/ml each year. This was accompanied by a mean fall in CD4 count of 78 cells/mm3 per year.

Increases in viral load were significantly greater (p < 0.001) in older patients. Each ten-year increase in age was associated with an additional 0.022 log10/copies/ml annual increase in viral load.

Overall, there was no association between sex, race or injecting drug use and viral load increase. However, there was some evidence of an age-sex interaction (p = 0.03). Viral load increased by a mean of 0.16 log10/copies/ml each year in women aged 55 and over, compared to a mean increase of 0.11 log10/copies/ml among men in this older age group.

Current viral load was the strongest predictor (p < 0.001) of CD4 decline. Each additional 1 log10/copies/ml increase in viral load was associated with a fall in CD4 cell count of 38 cells/mm3. Strikingly, the mean annual change in CD4 count was a fall of just 5 cells/mm3 among patients with a viral load below 200 copies/ml, compared to a drop of 225 cells/mm3 per year for patients with a viral load above 1 million copies/ml.

Age was a significant factor (p < 0.05) in the rate of CD4 decline, mean count dropping by an additional 1.7 cells/mm3 per year for each ten-year increase in age. Sex, race and injecting drug use were not associated with CD4 decline, nor was there any evidence of an interaction between these factors.

“In our study, we found in ART-naive individuals, faster viral load rise was associated with older age and faster CD4 depletion was strongly associated with a higher current viral load,” conclude the investigators. “These estimates, which largely confirm previous observations, also provide further data on factors associated with the natural course of HIV infection and, in particular, allow precise characterization of the mean rate of CD4 decline to be expected according to current viral load level.”


Natural History Project Writing Group for COHERE Factors associated with short-term changes in HIV viral load and CD4+ cell changes in antiretroviral-naïve individuals. AIDS 28, online edition. DOI: 10.1097/QAI.0000000000000224, 2014.

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