• Cerebrospinal Fluid HIV-1 RNA Levels Peak During Primary HIV-1 Infection (Slide Session 3)
  Authored by C. D. Pilcher, K. Robertson, C. Hall, P. Menezes, S. A. Fiscus, C. B. Hicks, and J. J. Eron
  View the original abstract

It has long been recognized that HIV invades the central nervous system (CNS) at an early stage of HIV infection and that this invasion may have significant implications regarding long-term neurologic function and may serve as a sanctuary site for HIV replication. A study presented at this conference evaluated the timing and extent of HIV infection of the CNS in primary HIV infection (PHI) and the effectiveness of antiretroviral therapy in controlling HIV in these patients. In addition, the levels of HIV RNA in the cerebrospinal fluid (CSF) and blood of patients with PHI were compared to those in patients with chronic HIV infection (CHI).

The seven PHI patients enrolled in this study were newly infected with HIV as evidenced by a positive HIV RNA or p24 antigen and a negative or evolving antibody test within 30 days. Only two of these patients had any neurological complaints, and those complaints were of headache.

The blood and cerebrospinal fluid (CSF) of six PHI patients were examined, with the first lumbar puncture approximately 39 days after the first PHI symptoms. Five of six of the patients had increased white blood cells in their CSF, predominantly lymphocytes. All of the PHI patients had measurable HIV RNA in their CSF (median HIV RNA 3.47 log10 copies/mL), whereas only 27 of 49 of the CHI patients did. The blood and CSF levels of HIV RNA were significantly higher in patients with PHI when compared with patients with CHI (regardless of the stage of CHI) and were highest in the patients who presented earliest with PHI. Blood and CSF levels of HIV RNA did not correlate well in PHI patients.

Antiretroviral treatment with didanosine (Videx, ddI), stavudine (Zerit, d4T) and nevirapine (Viramune) with or without hydroxyurea (Hydrea) led to a rapid decline in both blood and CSF HIV RNA levels. The CSF HIV RNA level was less than 50 copies/mL within four weeks of PHI patients starting antiretroviral therapy. The CSF pleocytosis also slowly resolved, although increased protein levels persisted.

The implications of the findings of this study are somewhat unclear. Intuitively, one would suspect that decreasing the HIV RNA and inflammation levels in the CSF during PHI may decrease the risk of subsequent risk of progressing to HIV-related neurologic dysfunction and may help, to some degree, in limiting the establishment of a latent reservoir in this area. However, at this point this has not been established and amounts to speculation. These crucial issues were not addressed in this study, and long-term follow-up of these patients (and perhaps a much larger cohort) may be needed to adequately answer some of the questions raised by the findings of this study. Finally, if preventing HIV from entering the CSF or quickly eliminating HIV from the CSF during PHI is important (which is likely to be the case), finding and treating new seroconverters may gain increasing importance.