Higher risk of neurocognitive problems in patients with lower CD4 nadirs

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A large US study in people with HIV has found that neurocognitive problems such as memory loss, poor concentration and slowed reactions are more common in people who had very low CD4 counts prior to starting treatment.

The study, presented last week at the Seventeenth Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco, found that in the majority of patients neurocognitive impairment detectable in tests was not easily recognised by either patient or doctor.

The CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study is a prospective observational study which enrolled a total of 1526 HIV-positive individuals at six sites in the United States.

Glossary

nadir

Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

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. 

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.

clinical trial

A research study involving participants, usually to find out how well a new drug or treatment works in people and how safe it is.

asymptomatic

Having no symptoms.

Seventy-seven per cent of the participants were male with a median age of 43, a median current CD4 cell count of 420 cells/mm3 and a median nadir (lowest-ever) CD4 cell count of 172 cells/mm3. Antiretroviral treatment (ART) was currently being taken by 71%, and 59% had an undetectable viral load.

Study participants were comprehensively assessed for neuropsychological (NP) impairments. HIV-associated neurocognitive disorders (HAND) were diagnosed and classified according to established (Frascati) criteria. Information was also collected on other opportunistic infections or conditions that could contribute to neurological impairment. Participants were classified as either NP impaired or unimpaired. Rates of neurocognitive impairment were high, being diagnosed in 52.4% of patients.

Within the 799 NP impaired, nearly a quarter (24.5%) had other major contributing conditions; of those who did not, most (71.0%) had asymptomatic impairment, 24.5% had minor neurocognitive disorder and only 4.5% had HIV-associated dementia.

Higher nadir CD4 cell counts were the only factor associated with lower rates of neurocognitive disorders; there was no such association with current CD4 cell counts. Impairment was significantly less common in those with a CD4 nadir ≥350 cells/mm3 than with a nadir <50 cells/mm3 (odds ratio [OR] 0.62, 95% confidence interval [CI], 0.45–0.84). (There was a steady trend toward less impairment at intermediate CD4 cell count ranges, but the differences did not reach statistical significance.)

The association remained significant even after adjustment for viral load, age, sex, ethnicity and duration of HIV infection, and was even stronger in the patients on ART with viral load < 50 copies/ml.

As this study was based on retrospective data, the investigators did state that a controlled clinical trial is needed to confirm their findings. However, this study strongly suggests that arresting CD4 cell count decline at levels above 350 cells/mm3 may protect against developing HIV-associated neurocognitive disorders later.

Further information

You can view the abstract on the official conference website.

You can also view a webcast and slides of this session on the official conference website.

References

Ellis R Higher CD4 nadir is associated with reduced rates of HIV-associated neurocognitive disorders in the CHARTER study: potential implications for early treatment initiation. 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 429, 2010.