Correlates of independent HIV-1 replication in the CNS and of its control by antiretrovirals

Luca, Andrea De; Ciancio, Bruno Christian; Larussa, Dora; Murri, Rita; Cingolani, Antonella; Rizzo, Maria Gabriella; Giancola, Maria Letizia; Ammassari, Adriana; Ortona, L

doi:10.1212/wnl.59.3.342

Cited by 81 publications

(53 citation statements)

References 33 publications

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“…No correlation between CSF and plasma viral load was observed in patients with higher viral replication in plasma and CSF. This fact was also reported by DE LUCA et al (2002) who found a correlation between CSF and plasma viral load, but this correlation was no longer observed when only patients with a high CSF (> 4.0 log 10 /mL) and plasma (> 5.0 log 10 /mL) viral load were included, and continued to be observed in those with lower CSF and plasma HIV-1 RNA levels.…”

Section: Discussionsupporting

confidence: 72%

“…Quantitative studies generally show higher mean and median HIV-1 RNA levels in plasma than in CSF, but higher CSF levels have been reported in certain cases (CINQUE et al 2000, DE LUCA et al 2002, LAFEUILLADE et al 1996, BURGER et al 1997. Some investigators found no correlation between CSF and plasma viral load (BREW et al 1997, ELLIS et al 1997, CINQUE et al 1998, MARTIN et al 1998, FOUDRAINE et al 1998, SCHRAGER et al 1998, ANTINORI et al 2002, while others did (McARTHUR et al 1997, BOSSI et al 1998, ROBERTSON et al 1998, GARCIA et al 1999.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of correlation between cerebrospinal fluid and plasma HIV-1 RNA levels in patients with neurological opportunistic diseases

Christo

Greco

Aleixo

et al. 2011

Rev. Inst. Med. trop. S. Paulo

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SUMMARYThe question of whether HIV-1 RNA in cerebrospinal fluid (CSF) is derived from viral replication in the central nervous system or simply reflects the transit of infected lymphocytes from the blood compartment has long been a matter of debate. Some studies found no correlation between CSF and plasma viral load, whereas others did. The lack of a correlation between the two compartments suggests that the presence of HIV-1 RNA is not simply due to the passive passage of the virus from blood to CSF but rather due to intrathecal replication. To evaluate the correlation between plasma and CSF HIV-1 RNA levels and to identify situations in which there is no correlation between the two compartments, seventy patients were prospectively studied. The association between CSF and plasma viral load was evaluated in the total population and in subgroups of patients with similar characteristics. A correlation between the CSF and plasma compartments was observed for patients undergoing highly active antiretroviral therapy (HAART), those with a CD4 T lymphocyte count lower than 200 cells/mm 3 , and those with increased CSF protein content. On the other hand, no correlation was observed for patients without adequate virological control, who had a CD4 count higher than 200 cells/mm 3 and who did not use HAART. The correlation between the two compartments observed in some patients suggests that CSF HIV-1 RNA levels may reflect plasma levels in these subjects. In contrast, the lack of a correlation between the two compartments in patients who were not on HAART and who had normal CSF proteins and a poor virological control possibly indicates compartmentalization of the virus in CSF and, consequently, plasma-independent intrathecal viral replication.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Analysis of correlation between cerebrospinal fluid and plasma HIV-1 RNA levels in patients with neurological opportunistic diseases

Christo

Greco

Aleixo

et al. 2011

Rev. Inst. Med. trop. S. Paulo

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“…The NRTIs zidovudine (AZT), stavudine, lamivudine, and abacavir-but not didanosine or zalcitabine-reach levels above the median inhibitory concentration (IC 50 ) [21,[25][26][27][28]. Of the six NRTIs, AZT appears most effective in crossing the blood-brain barrier, and its effects on the CNS are the most studied.…”

Section: Cns Penetration Of Several Drug Classesmentioning

confidence: 99%

“…Among the non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine penetrate the CSF more efficiently than delavirdine [21,[25][26][27]30]. Although these drugs are powerful anti-HIV agents due to their ability to bind to the site of reverse transcriptase and prevent replication, many adapted strains of the virus develop resistance.…”

Section: Cns Penetration Of Several Drug Classesmentioning

confidence: 99%

“…High protein binding in the plasma and the efflux actions of the P-glycoprotein pump appear to result in reduced CNS levels. CSF concentrations above IC 50 levels are reached by indinavir (IDV), but not by ritonavir (RTV), saquinavir, lopinavir (LPV), or nelfinavir (NFV) in many cases [21,[25][26][27]31,32]. However, some studies were able to detect adequate concentrations of RTV, LPV, and NFV in the CSF [33][34][35].…”

Section: Cns Penetration Of Several Drug Classesmentioning

confidence: 99%

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Effects of antiretroviral therapy on cognitive impairment

Liner¹,

Hall²,

Robertson

2008

Curr HIV/AIDS Rep

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Since the introduction of combination antiretroviral therapy, the manifestations of HIV-associated central nervous system (CNS) involvement have generally become less severe and more manageable. Patients initiating antiretroviral therapy have demonstrated improvement in cognitive functioning. Reduction of viral burden has been correlated with improved CNS functioning. Recent studies have focused on the importance of CNS-penetrating antiretroviral regimens to target active replication in this protected compartment. There were initial conflicting reports of whether CNS-penetrating antiretrovirals improved cognitive functioning, with more evidence supporting the importance of CNS penetration in reducing viral burden and improving cognitive outcomes. Cognitive loss remains a feature of HIV infection, and some patients still suffer from incident or progressing cognitive and motor dysfunction even on combination therapy. Because the virus enters the CNS within days of initial infection, latent infection may be chipping away at the brain during the long asymptomatic period in HIV. When to start antiretrovirals for the maximum cognitive benefit remains to be determined.

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Attenuated Central Nervous System Infection in Advanced HIV/AIDS With Combination Antiretroviral Therapy

et al. 2004

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In contrast to observations in individuals not treated with CART, we found no relationship between CSF markers and neurological status in this CART-using cohort with advanced HIV/AIDS. This was not explicable by demographic differences or plasma virological control. CART may substantially attenuate the degree of central nervous system HIV infection and immune activation, and in CART users, CSF HIV RNA and immune activation markers may fail to discriminate milder degrees of HIV-D and MCMD.

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Correlates of independent HIV-1 replication in the CNS and of its control by antiretrovirals

Cited by 81 publications

References 33 publications

Analysis of correlation between cerebrospinal fluid and plasma HIV-1 RNA levels in patients with neurological opportunistic diseases

Analysis of correlation between cerebrospinal fluid and plasma HIV-1 RNA levels in patients with neurological opportunistic diseases

Effects of antiretroviral therapy on cognitive impairment

Attenuated Central Nervous System Infection in Advanced HIV/AIDS With Combination Antiretroviral Therapy

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