|
8th Conference on Retroviruses and Opportunistic InfectionsChicago, IL - February 4 - 8, 2001 |
Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:43 (abstract no. 3)
C. D. Pilcher1, K. Robertson1, C. Hall1, P. Menezes1, S. A. Fiscus1, C. B. Hicks2, and J. J. Eron1
1Univ. of North Carolina, Chapel Hill and 2Duke Univ., Durham, NC.
BACKGROUND: Primary HIV infection (PHI) is characterized by rapid infection of lymphoid organs and secondary dissemination to peripheral tissues. In this study we investigated the timing and extent of viral dissemination to the CNS during PHI and assessed the effects of ART initiated during PHI within the CNS.
METHODS: Subjects had PHI defined by a positive HIV-1 RNA and a negative or evolving WB within 30 d. Subjects donated blood plasma (BP) and cerebrospinal fluid (CSF) for HIV-1 RNA (Roche Ultradirect; LL, <50 copies/ml) at baseline and on treatment with ddI, d4T, HU and NVP. Control subjects with untreated chronic HIV infection (CHI) donated CSF and BP.
RESULTS: 6 PHI patients donated CSF. 5 were symptomatic (none with neurologic symptoms) at the 1st lumbar puncture, with a median of 39 d from symptoms onset (range 14-70 d). 5 had elevated CSF protein and 3 had lymphocytic pleocytosis. CSF RNA was detected in 5/5 PHI subjects at baseline, vs 27/49 controls in CHI (p=0.07, Fisher's exact). Levels were significantly higher in PHI vs CHI in both BP [median (range) log copies/ml, 6.14 (4.43- 6.60) vs 3.99 (1.40-6.00); p<0.001, Mann-Whitney U)] and CSF [3.14 (2.18-3.95) vs 1.57 (<LL-4.18); p=0.03]. PHI significantly exceeded CHI CSF RNA (p<0.05) regardless of AIDS or neurologic symptoms in CHI. In PHI, RNA levels were highest closest to symptom onset in BP (r = -0.95, p=0.01, F-test) but were lowest close to symptom onset in CSF (r = 0.31, p=0.60). Correlation between CSF and BP RNA was poor (r = -0.22, p=0.73). CSF RNA was <LL in 4/4 by week 4 on ART. No CSF RNA rebound was seen on discontinuation of ART in two patients.
CONCLUSIONS: Peak level HIV production in CSF occurs during PHI but may be rapidly controlled with antiretroviral therapy. The apparent lack of correlation between RNA levels in CSF and BP in PHI may be explained by differential neurotropism or delayed dissemination of systemic infection to the CNS. ddI, d4T, HU and NVP can suppress HIV replication within the CNS in PHI.
2001-02-04
3
Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.