Human immunodeficiency virus (HIV)-1 invades the central nervous system (CNS) soon after infection and is partially protected there from host immunity and antiretroviral drugs (ARVs). Sanctuary from highly active antiretroviral therapy (HAART) in the CNS could result in ongoing viral replication, promoting the development of drug resistance and neurological disease. Despite the importance of these risks, no previous study has directly assessed HAART's effects on brain tissue viral load (VL). The authors evaluated 61 HIV-infected individuals for whom both histories of HAART treatment and postmortem brain tissue VL measurements were available. Two groups were defined based on HAART use in the 3 months prior to death: HAART(+) subjects had received HAART, and HAART(-) subjects had not received HAART. HIV RNA was quantified in postmortem brain tissue (log10 copies/10 microg total tissue RNA) and antemortem plasma (log10 copies/ml) by reverse transcriptase-polymerase chain reaction (RT-PCR). Brain tissue VLs were significantly lower among HAART(+) subjects compared to HAART(-) subjects (median 2.6 versus 4.1; P= .0007). These findings suggest that despite the limited CNS penetration of many antiretroviral medications, HAART is at least partially effective in suppressing CNS viral replication. Because some HAART regimens may be better than others in this regard, regimen selection strategies could be used to impede CNS viral activity, limit neuronal dysfunction, and prevent or treat clinical neurocognitive disorders in HIV-infected patients. Furthermore, such strategies might help to prevent the development of ARV resistance.
Background
Brazil accounts for the largest number of HIV+ persons in Latin America, and this epidemic poses a significant public health burden in this country. Little is known about the neuropsychiatric and functional consequences of HIV infection in this population.
Methods
Participants were 43 HIV+ and 29 HIV- individuals who underwent a neuropsychological, psychiatric and neurological evaluation that included self-report measures of mood (Beck Depression Inventory-II; BDI-II), neurocognitive complaints (Patient's Assessment of Own Functioning Inventory) and declines in instrumental activities of daily living (Activities of Daily Living questionnaire). The MINI-Plus generated Major depressive disorder (MDD) diagnoses. Apathy, defined as social withdrawal, decision-making difficulty, loss of interest and pleasure, was measured using items from the BDI-II and the neurological evaluation.
Results
When compared with seronegative participants, HIV+ individuals endorsed higher levels of apathy spectrum symptoms. After adjusting for mood and other covariates, apathy significantly predicted worse everyday functioning.
Limitations: The small sample size, along with the self-report measures used to evaluate apathy and functional difficulties limit the inferences that may be drawn from our findings.
Conclusions
Our Brazilian HIV+ cohort endorsed apathy and depression as well as significant functional complaints. Although correlated with depression, apathy was uniquely associated with functional difficulties. Clinical attention to apathy and depression in HIV-infected Brazilians may help identify patients at risk for functional difficulties who may benefit from additional support to maintain independence.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.