Effect of HAART in ADC. Graphs show the changes in plasma and CSF HIV-1 RNA concentrations (top panels), blood and CSF (middle panels), and composite quantitative neurological performance Z scores on four tests (QNPZ-4) [22, 127] (bottom panels) for 2 ADC patients after starting HAART. Patient 4033 (left column), a 38 year old man with ADC stage 2, was treated with abacavir, lamivudine, nevirapine and boosted indinavir. This led to a rapid fall in both CSF and plasma HIV and CSF neopterin concentrations from high baseline levels. During this same 3-month period, the patient improved neurologically (as documented by the rise in QNPZ-4) but he plateaued at an ‘impaired’ level of about -2, reflecting continued motor dysfunction including a mild spastic gait. He was able to return to school and to acting. Patient 5002 was 36 years old when he presented with ADC stage 3 and was treated with abacavir, lamivudine, nevirapine and nelfinavir. While there was an initial delay in the fall of his CSF HIV-1 RNA, it eventually fell to an undetectable level. Similarly, his CSF neopterin concentration declined from a high baseline. The QNPZ-4 score rose steadily over the first 3 months and continued further improvement over the remaining year, eventually reaching a normal level as he returned to a nearly asymptomatic functional level (ADC stage 0.5).

Effect of treatment on CSF HIV-1 RNA. These data are taken from Spudich et al [56] but are presented to show the relationships of plasma to CSF HIV-1 RNA in individual subjects (connecting lines). In those currently not receiving or those who have discontinued treatment, the relationships are highly variable as shown by the different slopes of the connecting lines. In those defined for this study as ‘failures’ (due to drug resistance) who are on treatment but with plasma HIV-1 RNA levels >500 copies per mL, the CSF HIV-1 RNA levels are consistently lower with a single exception. Successful suppression of plasma HIV-1 to < 500 copies per mL was accompanied by similar suppression of HIV-1 in the CSF with only a few exceptions.

CSF changes in HIV-1 infection. These cross-sectional data combine experience from two cohorts [5, 56] and include only untreated HIV-infected subjects. With the exception of 8 patients presenting with ADC (filled symbols), the remainder were neurologically asymptomatic. The graphs show the high prevalence of detectable CSF HIV-1 RNA across blood CD4+ T cell counts and its variable relationship to plasma HIV-1 RNA levels. The frequent presence of CSF pleocytosis is also shown. The vertical dotted line marks a blood CD4+ count of 50 cells per μL and shows the generally high plasma, lower CSF, and high plasma-CSF log10 difference in HIV-1 RNA, along with the lower incidence of pleocytosis.