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Background:  HIV-1 invades the central nervous system soon after infection and is partially protected there from host immunity and antiretroviral drugs. Sanctuary from HAART in the central nervous system might result in ongoing viral replication, thereby 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. We evaluated 61 HIV-infected individuals for whom both histories of HAART treatment and post-mortem brain tissue viral load measurements were available.

Methods:  Two groups were defined based on prospectively collected research data and retrospective clinical records review:  HAART(+) subjects had received HAART within 3 months prior to death, and HAART(–) subjects had not. HIV RNA was quantified in postmortem brain tissue (log₁₀ copies per 10 µg total tissue RNA) and antemortem plasma (log₁₀ copies per mL) by using RT-PCR.

Results:  Brain tissue viral loads were significantly lower among HAART(+) subjects as compared to HAART(-) subjects (median 2.6 vs 4.1; p = 0.0007). HAART treatment in close proximity to death also resulted in reductions in antemortem plasma viral load in the same patients, but effects on brain tissue viral load were statistically independent of those in plasma.

Conclusions:  These findings suggest that HAART is partially effective in suppressing central nervous system viral replication. Strategies for optimizing central nervous system viral inhibition will be important for managing HIV central nervous system disorders, including HIV dementia and milder neurocognitive impairment, and might help to prevent the development of antiretroviral drug resistance.

Keywords: Brain viral load; HIV; Antiretroviral therapy