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HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors


Heaton, Robert K., Franklin, Donald R., Ellis, Ronald J., McCutchan, J. Allen, Letendre, Scott L., Leblanc, Shannon, Corkran, Stephanie H., Duarte, Nichole A., Clifford, David B., Woods, Steven P., Collier, Ann C., Marra, Christina M., Morgello, Susan, Mindt, Monica Rivera, Taylor, Michael J., Marcotte, Thomas D., Atkinson, J. Hampton, Wolfson, Tanya, Gelman, Benjamin B., McArthur, Justin C., Simpson, David M., Abramson, Ian, Gamst, Anthony, Fennema-Notestine, Christine, Jernigan, Terry L., Wong, Joseph, Grant, Igor


Journal Of Neurovirology, Volume: 17, No.: 1, Pages.: 3-16

Year of Publication



Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV-) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV – participants from the pre-CART era (1988-1995; N = 857) and CART era (2000-2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.;

Bibtex Citation

@article{Heaton_2010, doi = {10.1007/s13365-010-0006-1}, url = {}, year = 2010, month = {dec}, publisher = {Springer Science $mathplus$ Business Media}, volume = {17}, number = {1}, pages = {3--16}, author = {Robert K. Heaton and Donald R. Franklin and Ronald J. Ellis and J. Allen McCutchan and Scott L. Letendre and Shannon LeBlanc and Stephanie H. Corkran and Nichole A. Duarte and David B. Clifford and Steven P. Woods and Ann C. Collier and Christina M. Marra and Susan Morgello and Monica Rivera Mindt and Michael J. Taylor and Thomas D. Marcotte and J. Hampton Atkinson and Tanya Wolfson and Benjamin B. Gelman and Justin C. McArthur and David M. Simpson and Ian Abramson and Anthony Gamst and Christine Fennema-Notestine and Terry L. Jernigan and Joseph Wong and Igor Grant}, title = {{HIV}-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors}, journal = {Journal of {NeuroVirology}} }


adult, aids dementia complex, antiretroviral, antiretroviral therapy highly active, associated, combination, complications, dementia, diagnosed, drug therapy, epidemiology, female, hiv, hiv infections, humans, longitudinal studies, male, middle aged, pathogenicity, population, prevalence, therapy, treatment outcome, using, young adult

Countries of Study


Types of Study

Case Control Study

Type of Outcomes


Type of Interventions

Risk Factor Modification

Risk Factor Modifications

At risk population