| 1. |
- Abdulle, Sahra, 1970, et al.
(författare)
-
Cerebrospinal fluid viral load and intrathecal immune activation in individuals infected with different HIV-1 genetic subtypes
- 2008
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HIV-1 exhibits a high degree of genetic diversity and is presently divided into 3 distinct HIV-1 genetic groups designated major (M), non-M/non-O (N) and outlier (O). Group M, which currently comprises 9 subtypes (A-D, F-H, J and K), at least 34 circulating recombinant forms (CRFs) and several unique recombinant forms (URFs) is responsible for most of the HIV-1 epidemic. Most of the current knowledge of HIV-1 central nervous system (CNS) infection is based on subtype B. However, subtypes other than subtype B account for the majority of global HIV-1 infections. Therefore, we investigated whether subtypes have any influence on cerebrospinal fluid (CSF) markers of HIV-1 CNS infection. METHODOLOGY/PRINCIPAL FINDINGS: CSF HIV-1 RNA, CSF neopterin and CSF white blood cell (WBC) count were measured in patients infected with different HIV-1 subtypes. Using multivariate regression analysis, no differences in the CSF WBC count, neopterin and viral load were found between various HIV-1 subtypes. CONCLUSIONS: We did not find any subtype-dependent differences in the markers evaluated in this study.
|
|
| 2. |
- Abdulle, Sahra, 1970, et al.
(författare)
-
Continuing intrathecal immunoactivation despite two years of effective antiretroviral therapy against HIV-1 infection
- 2002
-
Ingår i: Aids. ; 16:16, s. 2145-9
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the effect of antiretroviral combination treatment on intrathecal immunoactivation in HIV-1 infection. METHOD: Lumbar punctures were performed at baseline, and after 4 months, 1 and 2 years on 30 neurologically asymptomatic, treatment-naive HIV-1-infected patients started on antiretroviral treatment with three or more drugs. Levels of neopterin, beta2-microglobulin and HIV-1 RNA were measured in cerebrospinal fluid (CSF) and blood. RESULTS: All patients continued the study until the 4-month follow-up, although seven discontinued before the 1-year control, and an additional five discontinued before the control after 2 years. Neopterin, beta2-microglobulin and HIV-1 RNA decreased significantly both in CSF and blood, but although 100% of the patients decreased their CSF concentrations of beta2-microglobulin and HIV-1 RNA to normal levels, only 55% had normal CSF neopterin concentrations after 2 years treatment. CONCLUSIONS: In addition to CSF viral load, antiretroviral combination therapy substantially decreases the intrathecal immunoactivation as reflected by CSF neopterin and beta2-microglobulin in neuroasymptomatic HIV-1-infected patients. However, almost half of the patients still have slightly increased CSF neopterin concentrations after 2 years of effective treatment, which might reflect an ongoing low-grade viral replication in brain tissue.
|
|
| 3. |
- Abdurahman, Samir, 1965-, et al.
(författare)
-
Activity of the small modified amino acid alpha-hydroxy glycineamide on in vitro and in vivo human immunodeficiency virus type 1 capsid assembly and infectivity
- 2008
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 52:10, s. 3737-3744
-
Tidskriftsartikel (refereegranskat)abstract
- Upon maturation of the human immunodeficiency virus type 1 (HIV-1) virion, proteolytic cleavage of the Gag precursor protein by the viral protease is followed by morphological changes of the capsid protein p24, which will ultimately transform the virus core from an immature spherical to a mature conical structure. Virion infectivity is critically dependent on the optimal semistability of the capsid cone structure. We have reported earlier that glycineamide (G-NH(2)), when added to the culture medium of infected cells, inhibits HIV-1 replication and that HIV-1 particles with aberrant core structures were formed. Here we show that it is not G-NH(2) itself but a metabolite thereof, alpha-hydroxy-glycineamide (alpha-HGA), that is responsible for the antiviral activity. We show that alpha-HGA inhibits the replication of clinical HIV-1 isolates with acquired resistance to reverse transcriptase and protease inhibitors but has no effect on the replication of any of 10 different RNA and DNA viruses. alpha-HGA affected the ability of the HIV-1 capsid protein to assemble into tubular or core structures in vitro and in vivo, probably by binding to the hinge region between the N- and C-terminal domains of the HIV-1 capsid protein as indicated by matrix-assisted laser desorption ionization-mass spectrometry results. As an antiviral compound, alpha-HGA has an unusually simple structure, a pronounced antiviral specificity, and a novel mechanism of antiviral action. As such, it might prove to be a lead compound for a new class of anti-HIV substances.
|
|
| 4. |
- Albert, J., et al.
(författare)
-
Risk of HIV transmission from patients on antiretroviral therapy: A position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
- 2014
-
Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 46:10, s. 673-677
-
Tidskriftsartikel (refereegranskat)abstract
- The modern medical treatment of HIV with antiretroviral therapy (ART) has drastically reduced the morbidity and mortality in patients infected with this virus. ART has also been shown to reduce the transmission risk from individual patients as well as the spread of the infection at the population level. This position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy is based on a workshop organized in the fall of 2012. It summarizes the latest research and knowledge on the risk of HIV transmission from patients on ART, with a focus on the risk of sexual transmission. The risk of transmission via shared injection equipment among intravenous drug users is also examined, as is the risk of mother-to-child transmission. Based on current knowledge, the risk of transmission through vaginal or anal intercourse involving the use of a condom has been judged to be minimal, provided that the person infected with HIV fulfils the criteria for effective ART. This probably also applies to unprotected intercourse, provided that no other sexually transmitted infections are present, although it is not currently possible to fully support this conclusion with direct scientific evidence. ART is judged to markedly reduce the risk of blood-borne transmission between people who share injection equipment. Finally, the risk of transmission from mother to child is very low, provided that ART is started well in advance of delivery.
|
|
| 5. |
- Andersson, Elin, 1975, et al.
(författare)
-
Glycine-amide is an active metabolite of the antiretroviral tripeptide glycyl-prolyl-glycine-amide.
- 2005
-
Ingår i: Antimicrobial agents and chemotherapy. - 0066-4804. ; 49:1, s. 40-4
-
Tidskriftsartikel (refereegranskat)abstract
- The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH(2)) inhibits replication of human immunodeficiency virus (HIV) type 1 (HIV-1) in vitro, probably by interfering with capsid formation. The aim of the present study was to determine whether the metabolites glycyl-proline (GP-OH), glycine (G-OH), prolyl-glycine-amide (PG-NH(2)), proline (P-OH), and glycine-amide (G-NH(2)) from proteolytic cleavage may inhibit the replication of HIV-1 in vitro. PG-NH(2) has previously been shown to have a modest effect on HIV-1 replication. In the present study we show that G-NH(2) exhibits a pronounced inhibitory effect on HIV-1. This effect was not due to a decrease in cell proliferation or viability and could not be shown for herpes simplex virus type 1. The G-NH(2) concentration that inhibited virus replication by 50% (IC(50)) was equimolar to that of GPG-NH(2) and ranged from 3 to 41 microM. Transmission electron microscopy revealed that the effect of G-NH(2) on HIV-1 morphology was equivalent to that of GPG-NH(2) and showed disarranged capsid structures, indicating interference with capsid formation. Serial passage of HIV-infected cells with G-NH(2) for more than 20 subcultivations did not decrease the susceptibility to the compound. The results from this study suggest that GPG-NH(2) might act as a prodrug and that G-NH(2) is an active antiretroviral metabolite.
|
|
| 6. |
- Andersson, Elin, 1975, et al.
(författare)
-
No cross-resistance or selection of HIV-1 resistant mutants in vitro to the antiretroviral tripeptide glycyl-prolyl-glycine-amide.
- 2004
-
Ingår i: Antiviral research. - : Elsevier BV. - 0166-3542. ; 61:2, s. 119-24
-
Tidskriftsartikel (refereegranskat)abstract
- The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH(2)) inhibits replication of HIV-1 in vitro, probably by interfering with capsid formation. This study was aimed at determining cross-resistance between antiretroviral drugs and GPG-NH(2), and whether resistance to GPG-NH(2) can be induced in vitro. Fifty-five clinical HIV-1 isolates with different resistance-related mutations were tested for susceptibility to GPG-NH(2). No correlation between NRTI-, NNRTI- or PI-resistance and efficacy of GPG-NH(2) was found, indicating the lack of cross-resistance. Serial passages were performed with GPG-NH(2), and with lamivudine, and genotypic or phenotypic changes were determined. Resistance to lamivudine was detected after six passages. No resistance to GPG-NH(2) was generated after 30 passages in two parallel series. However, one mutation (T107I) in the p24 gene was detected in both series, but this mutation was not associated with decreased sensitivity to GPG-NH(2).
|
|
| 7. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
-
Higher HIV-1 RNA cutoff level required in cerebrospinal fluid than in blood to predict positive HIV-1 isolation
- 2000
-
Ingår i: J Med Virol. ; 62:1, s. 9-13
-
Tidskriftsartikel (refereegranskat)abstract
- HIV-1 can be isolated from the vast majority of blood samples taken from HIV-1-seropositive patients not treated with antiretroviral drugs. Isolation rates from cerebrospinal fluid (CSF) samples are considerably lower, ranging between 20-70%. The objective of this study was to determine the cutoff levels for HIV-1 RNA that would yield a positive predictive value > or =90% for positive virus isolation from CSF and blood. Quantitative HIV-1 RNA PCR (Amplicor HIV monitor, version 1.0, Roche Diagnostic Systems) and virus isolation were used to examine 303 CSF samples and 278 paired blood samples from 157 HIV-1-seropositive patients. Patients on antiretroviral treatment provided 140 of the CSF samples and 131 of the blood samples. CSF samples that were positive by culture numbered 137 of 303 (45%), as compared with 216 of 278 (78%) blood samples. In the case of samples taken from patients with antiretroviral treatment, 28% were positive by culture from CSF and 63% from blood. As expected, mean HIV-1 RNA levels were higher in CSF and blood samples positive by culture than in samples negative by culture. A cutoff level of >5,000 HIV-1 RNA copies/ml was required to yield a positive predictive value for positive virus isolation from CSF samples of > or =90%, whereas the cutoff level for blood samples was just above the detection limit of the assay (>200 HIV-1 copies/ml).
|
|
| 8. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
-
Increased blood-brain barrier permeability in neuro-asymptomatic HIV-1-infected individuals--correlation with cerebrospinal fluid HIV-1 RNA and neopterin levels
- 2001
-
Ingår i: J Neurovirol. ; 7:6, s. 542-7
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to assess the frequency of blood-brain barrier (BBB) impairment, as measured by the albumin ratio, in neuro-asymptomatic HIV-1-infected individuals without antiretroviral treatment and the correlation between BBB disruption and intrathecal immune activation and HIV-1 RNA levels. Serum and cerebrospinal fluid (CSF) albumin, neopterin, and HIV-1 RNA levels were analysed in 110 neuro-asymptomatic HIV-1-infected individuals at different stages of disease; 63 classified as CDC A, 25 as CDC B, and 22 as CDC C. Increased BBB permeability was found in 17 of 110 (15%) of HIV-1-infected individuals. This proportion was sustained throughout the CDC stages. The albumin ratio was correlated with the CSF neopterin levels (r(s) = 0.36, P < 0.001), the serum neopterin levels (r(s) = 0.37, P < 0.001), and the CSF HIV-1 RNA levels (r(s) = 0.26, P < 0.01), but not with the plasma HIV-1 RNA levels. The correlations between the albumin ratio and the CSF and serum neopterin concentrations and the CSF HIV-1 RNA levels indicate that immune activation and, possibly, intrathecal HIV-1 virus replication are important factors associated with increased BBB permeability in HIV-1 infection.
|
|
| 9. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
-
Increased cerebrospinal fluid protein tau concentration in neuro-AIDS
- 1999
-
Ingår i: J Neurol Sci. ; 171:2, s. 92-6
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Assessment of cerebrospinal fluid (CSF) levels of protein tau in human immunodeficiency virus type 1 (HIV-1) infection. MATERIAL AND METHODS: CSF tau levels were analyzed in 52 HIV-1-infected patients, 37 of whom had no neurological symptoms, eight had aquired immunodeficiency syndrome (AIDS) dementia complex (ADC), and seven had AIDS with other neurological complications. RESULTS: A significantly higher mean CSF tau concentration was found in patients with ADC (380 pg/ml) compared with patients with neuroasymptomatic HIV-1 infection (120 pg/ml, P<0.01) and HIV-negative controls (150 pg/ml, P<0.05). No difference in CSF tau levels was found between patients with ADC and patients with AIDS with other neurological complications. CONCLUSION: CSF tau might be used as a biochemical marker for axonal degeneration and might be of use to identify HIV-1-infected patients with ADC and other neurological complications, but it cannot discriminate between ADC and other neurological complications in HIV-1-infection.
|
|
| 10. |
- Arvidson, Nicklas, 1967, et al.
(författare)
-
Cerebrospinal fluid viral load, virus isolation, and intrathecal immunoactivation in HIV type 2 infection.
- 2004
-
Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 0889-2229 .- 1931-8405. ; 20:7, s. 711-5
-
Tidskriftsartikel (refereegranskat)abstract
- Four patients with HIV-2 infection were followed longitudinally with cerebrospinal fluid (CSF) analyses. Two patients had positive CSF HIV-2 isolations. These two patients had CD4 cell count below 200 x 10(6)/liter and maximum CSF HIV-2 RNA viral loads above 4000 copies/ml. Intrathecal immune activation was demonstrated by elevated CSF neopterin concentrations (14-18 nmol/liter). No opportunistic infections were diagnosed. After antiretroviral treatment CSF viral counts decreased to below 125 copies/ml and CSF neopterin concentrations decreased. In two other patients who had CD4 counts within the normal range CSF virus isolations were repeatedly negative and viral CSF loads were below 125 copies/ml. However, a slightly elevated CSF neopterin concentration in one sample and pleocytosis in another might also be caused by HIV-2 in these patients. Before antiretroviral treatment HIV-2 isolations from blood were positive in all four patients. Maximum HIV-2 RNA viral loads were higher in blood than in CSF. Treatment failure in one patient with increasing viral loads in blood did not result in viral rebound in CSF.
|
|
| 11. |
- Balzarini, Jan, et al.
(författare)
-
Obligatory involvement of CD26/dipeptidyl peptidase IV in the activation of the antiretroviral tripeptide glycylprolylglycinamide (GPG-NH(2)).
- 2004
-
Ingår i: The international journal of biochemistry & cell biology. - : Elsevier BV. - 1357-2725. ; 36:9, s. 1848-59
-
Tidskriftsartikel (refereegranskat)abstract
- GPG-NH2 and G-NH2 are highly selective antiretroviral agents in cell culture, and both compounds inhibit HIV replication in CEM cell cultures to an equal extent (50% effective concentration: approximately 30 microM). The lymphocyte surface glycoprotein marker CD26, which is identical to dipeptidyl peptidase IV, efficiently converted GPG-NH2 to G-NH2 releasing the dipeptide GP-OH. The closely related QPG-NH2 derivative was also inhibitory to HIV, presumably by the dipeptidyl peptidase IV (DPP IV)-catalyzed release of G-NH2. In contrast, the cyclic pQPG-NH2 derivative in which the glutamine at the amino terminal position of QPG-NH2 was replaced by pyroglutamine and which is resistant to cleavage by purified CD26, was devoid of antiviral activity. CD26 is abundantly expressed on a variety of HIV target cells and is also present in serum of bovine, murine and human origin. The CD26/DPP IV enzymatic activity in serum and in cell suspensions could be efficiently inhibited by the CD26/DPP IV inhibitor L-isoleucinepyrrolidine (IlePyr) with 50% inhibitory concentrations ranging between 20 and 100 microM. When combined in HIV-1-infected cell cultures, IlePyr and Diprotin A (DP-A), another CD26/DPP IV inhibitor, abrogated the antiviral activity of GPG-NH2 but not of G-NH2. Therefore, it was concluded that the anti-HIV drug GPG-NH2 is not active as such, but rather behaves as a prodrug that must be obligatorily cleaved by CD26/DPP IV to G-NH2 to exert its antiretroviral activity. This is the first demonstration of a lymphocyte activation/differentiation marker (i.e. CD26) that plays a direct regulatory and indispensable role in the eventual antiretroviral activity of small synthetic molecules such as the antiretroviral (pro)drug GPG-NH2.
|
|
| 12. |
- Caragounis, Eva Corina, et al.
(författare)
-
Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem
- 2008
-
Ingår i: Acta Neurol Scand. - : Hindawi Limited. - 1600-0404. ; 117:2, s. 108-16
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: HIV-1 infects the central nervous system (CNS) early in the course of infection. However, it is not known to what extent the virus evolves independently within the CNS and whether the HIV-RNA in cerebrospinal fluid (CSF) reflects the viral population replicating within the brain parenchyma or the systemic infection. The aim of this study was to investigate HIV-1 evolution in the CNS and the origin of HIV-1 in CSF. MATERIALS AND METHODS: Longitudinally derived paired blood and CSF samples and post-mortem samples from CSF, brain and spleen were collected over a period of up to 63 months from three HIV-1 infected men receiving antiretroviral treatment and presenting with symptoms of AIDS dementia complex (ADC). RESULTS: Phylogenetic analyses of HIV-1 V3, reverse transcriptase (RT) and protease sequences from patient isolates suggest compartmentalization with distinct viral strains in blood, CSF and brain. We found a different pattern of RT and accessory protease mutations in the systemic infection compared to the CNS. CONCLUSIONS: We conclude that HIV-1 may to some extent evolve independently in the CNS and the viral population in CSF mainly reflects the infection in the brain parenchyma in patients with ADC. This is of importance in understanding HIV pathogenesis and can have implications on treatment of HIV-1 patients.
|
|
| 13. |
- Edén, Arvid, 1975, et al.
(författare)
-
Asymptomatic Cerebrospinal Fluid HIV-1 Viral Blips and Viral Escape During Antiretroviral Therapy: A Longitudinal Study.
- 2016
-
Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 214:12, s. 1822-1825
-
Tidskriftsartikel (refereegranskat)abstract
- We examined longitudinal cerebrospinal fluid (CSF) samples (median, 5 samples/patients; interquartile range [IQR], 3-8 samples/patient) in 75 neurologically asymptomatic human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy. Twenty-seven patients (36%) had ≥1 CSF HIV RNA load of >20 copies/mL (23% had ≥1 load of >50 copies/mL), with a median HIV RNA load of 50 copies/mL (IQR, 32-77 copies/mL). In plasma, 42 subjects (52%) and 22 subjects (29%) had an HIV RNA load of >20 and >50 copies/mL, respectively. Two subjects had an increasing virus load in consecutive CSF samples, representing possible CSF escape. Of 418 samples, 9% had a CSF HIV RNA load of >20 copies/mL (5% had a load of >50 copies/mL) and 19% had a plasma HIV RNA load of >20 copies/mL (8% had a load of >50 copies/mL). A CSF-associated virus load of >20 copies/mL was associated with higher CSF level of neopterin. In conclusion, CSF escape was rare, and increased CSF HIV RNA loads usually represented CSF virus load blips.
|
|
| 14. |
- Edén, Arvid, 1975, et al.
(författare)
-
HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.
- 2010
-
Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 202:12, s. 1819-25
-
Tidskriftsartikel (refereegranskat)abstract
- Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank.
|
|
| 15. |
- Edén, Arvid, 1975, et al.
(författare)
-
Reply to Seligman
- 2011
-
Ingår i: J Infect Dis. ; 2011:1, s. 174-175
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 16. |
- Felldin, Marie, et al.
(författare)
-
Antibody persistence 1year after pandemic H1N1 2009 influenza vaccination and immunogenicity of subsequent seasonal influenza vaccine among adult organ transplant patients.
- 2014
-
Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277. ; 27:2, s. 197-203
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the antibody persistence in solid organ transplant (SOT) recipients 1year after immunization with two doses of monovalent AS03-adjuvanted influenza A(H1N1)pdm09 vaccine. We also assessed the boosting effect of the seasonal trivalent inactivated vaccine 2010 (TIV/10) that contained the influenza A(H1N1)pdm09 strain. A total of 49 SOT recipients and 11 healthy controls were included. After a blood sample was obtained to assess the persistent immunity, one dose of TIV/10 was administered and another blood sample was collected 1month after vaccination. A(H1N1)pdm09 antibodies were measured using a haemagglutination inhibition assay. The percentage of SOT recipients with protective titres decreased between 1month and 10-14months after the monovalent influenza A(H1N1)pdm09 vaccination, from 79% (n=38) to 47% (n=23) (P=0.02). The corresponding numbers for the control group were 100% and 63%, respectively (P=0.008). After the TIV/10 boosting dose, the number of SOT recipients with protective titres increased from 47% (n=23) to 71% (n=35) (P=0.2). All the controls reached a protective titre level. The median titre rise was significantly higher among controls when compared to SOT recipients (P=0.0036). No rejection or adverse events were seen. The results show an obvious need for vaccine boosting doses in the SOT patients. (ClinicalTrials.gov number: NCT01256931).
|
|
| 17. |
- Gisslén, Magnus, 1962, et al.
(författare)
-
Cerebrospinal fluid and plasma viral load in HIV-1-infected patients with various anti-retroviral treatment regimens
- 2000
-
Ingår i: Scand J Infect Dis. ; 32:4, s. 365-9
-
Tidskriftsartikel (refereegranskat)abstract
- Highly active anti-retroviral therapy (HAART) effectively decreases HIV-1 RNA in cerebrospinal fluid (CSF) and plasma in controlled clinical trials. To study the virological effect in CSF and plasma achieved in routine practice, HIV-1 RNA levels were analysed retrospectively in 27 patients on mono-nucleoside reversed transcriptase inhibitor (NRTI) treatment, 27 on dual-NRTI-treatment and 45 on HAART using a Roche Amplicor HIV-1 monitor quantitative PCR. A significant difference was found in the proportion of patients with a CSF viral load below 20 copies/ml between patients treated with 1 (0%) and 2 NRTIs (41%) as well as between those treated with 2 NRTIs and HAART (69%). The proportion of patients with plasma viral load below 20 copies/ml differed significantly between patients on HAART (47%) and those on 2 NRTIs (0%), but not between those with 1 (0%) or 2 NRTIs. In multivariate regression analysis, treatment regimen and prior anti-retroviral experience (but not treatment time) were independently associated with the CSF viral load. Plasma viral load was independently associated with treatment regimen and treatment time, but not with anti-retroviral experience. Dual-NRTI-treatment affects the CSF viral load substantially, while HAART is required to achieve an essential decline in plasma viral load.
|
|
| 18. |
- Gisslén, Magnus, 1962, et al.
(författare)
-
Cerebrospinal fluid viral breakthrough in two HIV-infected subjects on darunavir/ritonavir monotherapy.
- 2012
-
Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 44:12, s. 997-1000
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Darunavir/ritonavir monotherapy maintains HIV suppression in most patients who have achieved an undetectable viral load on combination antiretroviral treatment, and is increasingly used in the clinic. However, concerns have been raised about the effectiveness of ritonavir-boosted protease inhibitor (PI/r) monotherapy in the prevention of HIV replication in the central nervous system (CNS). Here we report the cases of 2 patients on darunavir/r maintenance monotherapy with cerebrospinal fluid viral breakthrough together with increased immunoactivation and biomarker signs of neuronal injury. These 2 cases raise concerns about the effectiveness of darunavir/ritonavir monotherapy in HIV CNS infection. Thus, we recommend caution with protease inhibitor monotherapy until CNS results have been obtained from clinical studies.
|
|
| 19. |
- Gisslén, Magnus, 1962, et al.
(författare)
-
Cerebrospinal fluid viral load in HIV-1-infected patients without antiretroviral treatment: a longitudinal study
- 1998
-
Ingår i: J Acquir Immune Defic Syndr Hum Retrovirol. ; 17:4, s. 291-5
-
Tidskriftsartikel (refereegranskat)abstract
- HIV-1 RNA and neopterin levels were observed longitudinally for 20 to 68 months (mean, 37.5 months) in cerebrospinal fluid (CSF) and serum in 15 HIV-1-infected patients not receiving antiretroviral treatment. During the course of infection the HIV-1 RNA levels increased significantly in CSF, from a mean of 3.08 to 3.51 log10 copies RNA/ml (p < .01). A significant positive correlation was found between the CSF levels of HIV-I RNA and neopterin (rs = 0.54; p < .001), which increased from 13.6 to 19.6 nmol/L (p < .01). No significant changes in HIV-1 RNA or neopterin levels were found in serum. We suggest that the increase of CSF viral load with time in HIV-1 infection triggers an intrathecal immune activation reflected by increased CSF levels of neopterin. These results are in accordance with the theory that a chronic immune stimulation within the central nervous system (CNS) is involved in the pathogenesis of neurologic HIV-1 disease.
|
|
| 20. |
- Gisslén, Magnus, 1962, et al.
(författare)
-
Cerebrospinal fluid viral load, intrathecal immunoactivation, and cerebrospinal fluid monocytic cell count in HIV-1 infection
- 1999
-
Ingår i: J Acquir Immune Defic Syndr. ; 21:4, s. 271-6
-
Tidskriftsartikel (refereegranskat)abstract
- To assess the association between cerebrospinal fluid (CSF) viral load, intrathecal immunoactivation, and immunosuppression in HIV-1-infected individuals with no antiretroviral treatment experience a cross-sectional study of stored frozen CSF and plasma samples were conducted. The study population included a total of 120 antiretroviral-naive HIV-1-infected patients, 110 neuroasymptomatic patients, and 10 with neurologic complications. HIV-1 RNA was quantified in cell-free CSF and plasma using polymerase chain reaction (PCR; Roche Amplicor HIV-1 Monitor version 1.5, Roche Diagnostic Systems, Hoffmann-La Roche, Inc., Base, Switzerland). Immunoactivation was measured by CSF-serum IgG index, CSF neopterin concentrations, and CSF monocytic cell count. The CSF HIV-1 RNA load did not differ significantly between patients with or without neurologic complications. In patients without neurologic symptoms, the CSF monocytic cell counts were correlated to the CSF viral load (r(s) = 0.40, p < .001), whereas IgG index and CSF neopterin concentrations were correlated to the viral load only in the subgroup of patients with CD4 counts > or =200 x 10(6) cells/L. In this subgroup of patients, the peripheral CD4 cell count was, as expected, inversely correlated to the CSF viral load (r. = -0.36, p < .01), whereas in patients with CD4 counts <200 x 10(6) cells/L, an unexpected, significant positive correlation (r(s) = 0.43, p < .01 ) was found. In HIV-1-infected patients with neurologic complications, no significant correlations were found between immune activation, CSF viral load, and immunosuppression.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Gisslén, Magnus, 1962, et al.
(författare)
-
Markers of immune stimulation in the cerebrospinal fluid during HIV infection: a longitudinal study
- 1994
-
Ingår i: Scand J Infect Dis. - : Informa UK Limited. ; 26:5, s. 523-33
-
Tidskriftsartikel (refereegranskat)abstract
- Markers of immune stimulation were studied in 76 sequential cerebrospinal fluid (CSF) samples from 19 patients infected with HIV-1 without antiretroviral treatment during observation periods ranging from 22 months to 6 years. Eight of these patients were further followed with 14 CSF samples for 3-24 months of zidovudine treatment. During the course of HIV-1 infection, the mean CSF neopterin and beta 2-microglobulin (beta 2M) concentrations increased from 12.7 to 20.4 nmol/l (p < 0.01) and from 1.93 to 2.17 mg/l (p < 0.05), respectively, while the mean peripheral CD4 + T cell count decreased from 624 to 320 cells x 10(6)/l (p < 0.001). The IgG index, reflecting intrathecal immunoglobulin production, increased from 0.72 to 0.92 (p = 0.08). The number of patients with CSF pleocytosis did not change significantly during follow-up (8/19 at baseline, 7/19 at endpoint). In the 8 patients followed up during antiretroviral treatment, a significant reduction in mean CSF levels of neopterin and beta 2M (-48% and -32%, respectively, p < 0.01) was seen after 3-12 months on zidovudine. We suggest that gradual increase in immune stimulation reflected by the rising CSF concentrations of neopterin and beta 2M indicates that HIV-1 infection in the central nervous system is progressive even in neurologically asymptomatic stages.
|
|
| 24. |
|
|
| 25. |
- Gisslén, Magnus, 1962, et al.
(författare)
-
The effect on human immunodeficiency virus type 1 RNA levels in cerebrospinal fluid after initiation of zidovudine or didanosine
- 1997
-
Ingår i: J Infect Dis. ; 175:2, s. 434-7
-
Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus type 1 (HIV-1) RNA, neopterin, and beta2-microglobulin levels were analyzed in cerebrospinal fluid (CSF) and serum before and 3-13 months after initiation of antiretroviral monotherapy in 16 HIV-1-infected persons. Twenty-one treatment periods, 13 after initiation of zidovudine and 8 after initiation of didanosine, were studied. During zidovudine treatment, CSF HIV RNA levels decreased by a mean of 1.05 log10 (-91%, P < .01), and CSF neopterin and beta2-microglobulin levels by 57% and 33%, respectively (P < .01). No reduction was seen during didanosine treatment in CSF HIV RNA (+0.13 log10, not significant), CSF neopterin, or beta2-microglobulin levels. Changes in CSF HIV RNA levels correlated with changes in CSF neopterin and beta2-microglobulin (r(s) = .81 and .83, respectively, P < .001). The decrease in HIV RNA was significantly larger in CSF than in serum following zidovudine treatment (P < .01). These data demonstrate that zidovudine is a potent reducer of central nervous system virus load, which may be important for long-term neuroprotection.
|
|
| 26. |
- Görander, Staffan, 1952, et al.
(författare)
-
Secreted portion of glycoprotein g of herpes simplex virus type 2 is a novel antigen for type-discriminating serology.
- 2003
-
Ingår i: Journal of clinical microbiology. - 0095-1137. ; 41:8, s. 3681-6
-
Tidskriftsartikel (refereegranskat)abstract
- The secreted portion of glycoprotein G (sgG-2) of herpes simplex virus type 2 (HSV-2) was evaluated as a novel antigen in an enzyme-linked immunosorbent assay (ELISA) format for detection of type-specific immunoglobulin G (IgG) antibodies in HSV-2-infected patients. The results were compared with those obtained by a commercially available assay, the HerpeSelect 2 ELISA (the FOCUS2 assay). Five different panels of sera were analyzed: panel A consisted of 109 serum samples from patients with a culture-proven HSV-1 infection that were Western blotting (WB) negative for HSV-2; panel B consisted of 106 serum samples from patients with a culture-proven recurrent HSV-2 infection that were WB positive for HSV-2; panel C consisted of 100 serum samples with no detectable IgG antibodies against HSV-1 and HSV-2; panel D consisted of 70 HSV-2 negative "tricky" serum samples containing antinuclear IgG antibodies or IgM antibodies against other viruses or bacteria; and panel E consisted of consecutive serum samples from 21 patients presenting with a first episode of HSV-2-induced lesions. When sera in panels A to C were analyzed, the sgG-2 ELISA and the FOCUS2 assay both showed sensitivities and specificities of >or=98%. In total, among the samples in panel D, 13 serum samples (19%) were false positive by the FOCUS2 assay and 1 serum sample (1.4%) was false positive by the sgG-2 ELISA. When the sera in panel E were analyzed, the sgG-2 ELISA detected seroconversion somewhat later than WB or the FOCUS2 assay did. We conclude that sgG-2 induces an HSV-2 type-specific antibody response and can be used for type-discriminating serology.
|
|
| 27. |
- Hagberg, Lars, 1951, et al.
(författare)
-
Intrathecal immunoactivation in patients with HIV-1 infection is reduced by zidovudine but not by didanosine
- 1996
-
Ingår i: Scand J Infect Dis. - : Informa UK Limited. ; 28:4, s. 329-33
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of zidovudine and didanosine on the cerebrospinal fluid (CSF) concentrations of neopterin was studied in 12 patients with human immunodeficiency virus type-1 (HIV-1) infection 3-12 months after initiation of antiretroviral therapy. Ten treatment periods on zidovudine and 7 on didanosine were analysed. The CSF concentrations of neopterin decreased by 63% (from 29.6 to 12.9 nmol/l, p < 0.01) during zidovudine but increased by 15% (from 22.6 to 25.9 nmol/l, not significant during didanosine treatment. The CSF monocytic cell count decreased during zidovudine but increased during didanosine treatment. The results suggest that zidovudine but not didanosine reduces intrathecal immunoactivation during HIV-1 infection.
|
|
| 28. |
- Hagberg, Lars, 1951, et al.
(författare)
-
Kinetics of HIV-1 in cerebrospinal fluid and serum after zidovudine treatment
- 1999
-
Ingår i: J NeuroAIDS. ; 2:2, s. 29-35
-
Tidskriftsartikel (refereegranskat)abstract
- Two patients with HIV-1 infection associated with neurological complications were repeatedly followed with cerebrospinal fluid (CSF) and serum analyses before, and 1 to 2.5 years after single zidovudine treatment. Retrospectively, HIV-RNA levels were analyzed with quantitative PCR assay. The number of HIV-RNA copies in CSF was decreased already 1 week after initiation of zidovudine, and continued to decrease during 5 months of follow up, while the serum levels increased during the same period. The difference between HIV levels in CSF and serum compartments following zidovudine treatment indicates that the CSF viral load does not merely reflect blood levels. Single zidovudine treatment did not reduce the viral load in CSF to non-detectable levels but had a better and more long-lasting anti-HIV effect in CSF than in peripheral blood.
|
|
| 29. |
- Josephson, Filip, et al.
(författare)
-
Antiretroviral treatment of HIV infection: Swedish recommendations 2007.
- 2007
-
Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:6-7, s. 486-507
-
Tidskriftsartikel (refereegranskat)abstract
- On 3 previous occasions, in 2002, 2003 and 2005, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. An expert group, under the guidance of RAV, has now revised the text again. Since the publication of the previous treatment recommendations, 1 new drug for the treatment of HIV has been approved - the protease inhibitor (PI) darunavir (Prezista). Furthermore, 3 new drugs have become available: the integrase inhibitor raltegravir (MK-0518), the CCR5-inhibitor maraviroc (Celsentri), both of which have novel mechanisms of action, and the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (TMC-125). The new guidelines differ from the previous ones in several respects. The most important of these are that abacavir is now preferred to tenofovir and zidovudine, as a first line drug in treatment-naïve patients, and that initiation of antiretroviral treatment is now recommended before the CD4 cell count falls below 250/microl, rather than 200/microl. Furthermore, recommendations on the treatment of HIV infection in children have been added to the document. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels).
|
|
| 30. |
- Josephson, Filip, et al.
(författare)
-
Treatment of HIV infection: Swedish recommendations 2009.
- 2009
-
Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 41:11-12, s. 788-807
-
Forskningsöversikt (refereegranskat)abstract
- On 4 previous occasions, in 2002, 2003, 2005 and 2007, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. In November 2008, an expert group under the guidance of RAV once more revised the guidelines, of which this is a translation into English. The most important updates in the present guidelines include the following: (a) treatment initiation is now recommended at a CD4 cell count of approximately 350/microl; (b) new recommendations for first-line therapy: abacavir/lamivudine or tenofovir/emtricitabine in combination with efavirenz or a boosted protease inhibitor (PI/r); (c) an increased focus on reducing the use of antiretroviral drugs that may cause lipoatrophy; (d) an emphasis on quality assurance of HIV care through the use of InfCare HIV; (e) considerably altered recommendations for the initiation of antiretroviral therapy in children. All infants (<1 y) should start antiretroviral therapy, regardless of immune status. Also, absolute CD4+ cell counts, rather than percentage, may be used to guide treatment initiation in children above the age of 5 y.
|
|
| 31. |
- Karlsson, Ulf, et al.
(författare)
-
Mode of coreceptor use by R5 HIV type 1 correlates with disease stage: a study of paired plasma and cerebrospinal fluid isolates.
- 2009
-
Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 25:12, s. 1297-1305
-
Tidskriftsartikel (refereegranskat)abstract
- Through the use of chimeric CXCR4/CCR5 receptors we have previously shown that CCR5-tropic (R5) HIV-1 isolates acquire a more flexible receptor use over time, and that this links to a reduced viral susceptibility to inhibition by the CCR5 ligand RANTES. These findings may have relevance with regards to the efficacy of antiretroviral compounds that target CCR5/virus interactions. Compartmentalized discrepancies in coreceptor use may occur, which could also affect the efficacy of these compounds at specific anatomical sites, such as within the CNS. In this cross-sectional study we have used wild-type CCR5 and CXCR4 as well as chimeric CXCR4/CCR5 receptors to characterize coreceptor use by paired plasma and cerebrospinal fluid (CSF) isolates from 28 HIV-1-infected individuals. Furthermore, selected R5 isolates, with varying chimeric receptor use, were tested for sensitivity to inhibition by the CCR5 antagonist TAK-779. Discordant CSF/plasma virus coreceptor use was found in 10/28 patients. Low CD4+ T cell counts correlated strongly with a more flexible mode of R5 virus CCR5 usage, as disclosed by an increased ability to utilize chimeric CXCR4/CCR5 receptors, specifically receptor FC-2. Importantly, an elevated ability to utilize chimeric receptors correlated with a reduced susceptibility to inhibition by TAK-779. Our findings show that a discordant CSF and plasma virus coreceptor use is not uncommon. Furthermore, we provide support for an emerging paradigm, where the acquisition of a more flexible mode of CCR5 usage is a key event in R5 virus pathogenesis. This may, in turn, negatively impact the efficacy of CCR5 antagonist treatment in late stage HIV-1 disease.
|
|
| 32. |
- Lindkvist, Annica, et al.
(författare)
-
Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study
- 2009
-
Ingår i: AIDS research and therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The latency of HIV-1 in resting CD4+ T-lymphocytes constitutes a major obstacle for the eradication of virus in patients on antiretroviral therapy (ART). As yet, no approach to reduce this viral reservoir has proven effective. METHODS: Nine subjects on effective ART were included in the study and treated with high dosage intravenous immunoglobulin (IVIG) for five consecutive days. Seven of those had detectable levels of replication-competent virus in the latent reservoir and were thus possible to evaluate. Highly purified resting memory CD4+ T-cells were activated and cells containing replication-competent HIV-1 were quantified. HIV-1 from plasma and activated memory CD4+ T-cells were compared with single genome sequencing (SGS) of the gag region. T-lymphocyte activation markers and serum interleukins were measured. RESULTS: The latent HIV-1 pool decreased with in median 68% after IVIG was added to effective ART. The reservoir decreased in five, whereas no decrease was found in two subjects with detectable virus. Plasma HIV-1 RNA >or= 2 copies/mL was detected in five of seven subjects at baseline, but in only one at follow-up after 8-12 weeks. The decrease of the latent HIV-1 pool and the residual plasma viremia was preceded by a transitory low-level increase in plasma HIV-1 RNA and serum interleukin 7 (IL-7) levels, and followed by an expansion of T regulatory cells. The magnitude of the viral increase in plasma correlated to the size of the latent HIV-1 pool and SGS of the gag region showed that viral clones from plasma clustered together with virus from activated memory T-cells, pointing to the latent reservoir as the source of HIV-1 RNA in plasma. CONCLUSION: The findings from this uncontrolled proof-of-concept study suggest that the reservoir became accessible by IVIG treatment through activation of HIV-1 gene expression in latently-infected resting CD4+ T-cells. We propose that IVIG should be further evaluated as an adjuvant to effective ART.
|
|
| 33. |
- Lycke, Jan, 1956, et al.
(författare)
-
Acyclovir treatment of relapsing-remitting multiple sclerosis. A randomized, placebo-controlled, double-blind study.
- 1996
-
Ingår i: Journal of neurology. - 0340-5354. ; 243:3, s. 214-24
-
Tidskriftsartikel (refereegranskat)abstract
- Acyclovir treatment was used in a randomized, double-blind, placebo-controlled clinical trial with parallel groups to test the hypothesis that herpes virus infections are involved in the pathogenesis of multiple sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or placebo tablets three times daily for 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological examinations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on "intent-to-treat" data and the primary outcome measure was the exacerbation rate. In the acyclovir group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo group (n = 30) had 94 exacerbations and an annual exacerbation rate of 1.57. Thus, 34% fewer exacerbations were encountered during acyclovir treatment. This difference in exacerbation rate between the treatment groups was not significant (P = 0.083). However, this trend to a lower disease activity in acyclovir-treated patients was supported in subsequent data analysis. If the patients were grouped according to exacerbation frequencies, i.e. into low (0-2), medium (3-5) and high (6-8) rate groups, the difference between acyclovir and placebo treatment was significant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbation rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (n = 19) and placebo (n = 20) patients and acyclovir-treated patients showed a significant reduction of exacerbations (P = 0.024). Otherwise, neurological parameters were essentially unaffected by acyclovir treatment and there were no convincing signs of reduced neurological deterioration in the acyclovir group. This study indicates that acyclovir treatment might inhibit the triggering of MS exacerbations and thus suggests that acyclovir-susceptible viruses might be involved in the pathogenesis of MS. This possibility warrants further investigation.
|
|
| 34. |
- Mellberg, Tomas, et al.
(författare)
-
HIV-1 low copy viral sequencing-a prototype assay
- 2016
-
Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 48:6, s. 472-478
-
Tidskriftsartikel (refereegranskat)abstract
- In HIV-1 patients with low viral burden, sequencing is often problematic, yet important. This study presents a sensitive, sub-type independent system for sequencing of low level viremia. Sequencing data from 32 HIV-1 infected patients with low level viremia were collected longitudinally. A combination of ViroSeq HIV-1 Genotyping System and an in-house nesting protocol was used. Eight sub-types were represented. The success-rate of amplification of both PR and RT in the same sample was 100% in samples with viral loads above 100 copies/ml. Below 100 copies/ml, this study managed to amplify both regions in 7/13 (54%) samples. The assays were able to amplify either PR or RT in all sub-types included but one sub-type A specimen. In conclusion, this study presents a promising, simple assay to increase the ability to perform HIV-1 resistance testing at low level viremia. This is a prototype assay and the method needs further testing to evaluate clinical performance. © 2016 Society for Scandinavian Journal of Infectious Diseases.
|
|
| 35. |
- Mellberg, Tomas, et al.
(författare)
-
Rebound of residual plasma viremia after initial decrease following addition of intravenous immunoglobulin to effective antiretroviral treatment of HIV
- 2011
-
Ingår i: AIDS Research and Therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Background High dosage of intravenous immunoglobulin (IVIG) has been observed as a possible activator of HIV gene expression in latently infected resting CD4+ T-cells, leading to a substantial decrease in both the reservoir and the residual plasma viremia when added to effective ART. IVIG treatment has also been reported to expand T regulatory cells (Tregs). The aim of this study was to evaluate possible long-term effect of IVIG treatment on residual viremia and T-lymphocyte activation. Methods Nine HIV-infected subjects on effective ART included in a previously reported study on IVIG treatment were evaluated 48-104 weeks after therapy. In addition, 14 HIV-infected controls on suppressive ART were included. HIV-1 RNA was analyzed in cell-free plasma by using an ultrasensitive PCR-method with a detection limit of 2 copies/mL. T-lymphocyte activation markers and serum interleukins were measured. Results Plasma residual viremia rebounded to pre-treatment levels, 48-104 weeks after the initial decrease that was observed following treatment with high-dosage IVIG. No long-term effect was observed regarding T-lymphocyte activation markers, T-regulatory cells or serum interleukins. In a post-hoc analysis, a correlation between plasma HIV-1-RNA and CD4+ T-cell count was found in both IVIG-treated patients and controls. Conclusions These results indicate that the decrease in the latent HIV-1 pool observed during IVIG treatment is transient. Although not our primary objective, we found a correlation between HIV-1 RNA and CD4+ T-cell count suggesting the possibility that patients with a higher CD4+ T-cell count might harbor a larger residual pool of latently infected CD4+ T-cells.
|
|
| 36. |
|
|
| 37. |
- Su, J, et al.
(författare)
-
The nontoxic tripeptide glycyl-prolyl-glycine amide inhibits the replication of human immunodeficiency virus type 1.
- 2001
-
Ingår i: Journal of human virology. - 1090-9508. ; 4:1, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether short peptides corresponding to the RGPGR motif of the V3 loop of gp 120 have anti-human immunodeficiency virus type 1 (anti-HIV-1) activity. DESIGN/METHODS: Short peptides were tested against the HIV-1 laboratory strains and clinical isolates. RESULTS: The tripeptide glycyl-prolyl-glycine amide (GPG-NH2) inhibited the replication of both laboratory strains and 47 clinical isolates, including 19 strains that were resistant to other drugs or that were from patients with failing therapy. The 50% inhibitory concentrations values were 2.7 to 37 microM. Phenotypic change of two isolates from nonsyncytia-inducing to syncytia-inducing did not change their sensitivity to GPG-NH2. The tripeptide added to the antiviral effect of both zidovudine and ritonavir. CONCLUSIONS: The tripeptide GPG-NH2 is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action. Glycyl-prolyl-glycine-NH2 might prove useful by itself or as a lead compound for the treatment of drug-resistant HIV-1. Glycyl-prolyl-glycine-NH2 is currently undergoing phase I/II human clinical trials in Sweden.
|
|
| 38. |
- Trybala, Edward, 1955, et al.
(författare)
-
Structural and functional features of the polycationic peptide required for inhibition of herpes simplex virus invasion of cells.
- 2004
-
Ingår i: Antiviral research. - : Elsevier BV. - 0166-3542. ; 62:3, s. 125-34
-
Tidskriftsartikel (refereegranskat)abstract
- Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) mediates initial virus contact with cells by binding to heparan sulfate (HS) chains. The synthetic peptide 137GSRVQIRCRFRNSTR151 overlapping a major part of the HS-binding site of gC inhibited HSV-1 infection and, to some extent, HSV-2 infection of cells. Experiments on mutant, glycosaminoglycan-deficient cells as well as the binding assays involving peptide and purified cell surface components identified HS, and, to a lesser degree, chondroitin sulfate as sites of peptide activity. Anti-HSV-1 activity of the peptide was due to (i) partial inhibition of virus binding to cells and (ii) arresting the virions, which managed to attach to the cells in the presence of peptide, at a step of initial relatively weak binding. Analysis of the ionic-strength dependence of the peptide-HS and the virus-HS interactions revealed that the more efficient inhibition by the peptide of HSV-1 than HSV-2 infectivity was due to a relatively high affinity of HSV-2 for HS, a feature of importance in overcoming the peptide block. Mutational analysis of viral gC and peptide variants identified, apart from basic amino acids, two hydrophobic residues Ile(142) and Phe(146) as important in maintaining the specific affinity of peptide for HS and, hence, its anti-HSV activity. These results could contribute to the development of anti-HSV compounds that target initial events in the virus-cell interaction.
|
|
| 39. |
- Yilmaz, Aylin, 1974, et al.
(författare)
-
Cerebrospinal fluid and plasma HIV-1 RNA levels and lopinavir concentrations following lopinavir/ritonavir regimen.
- 2004
-
Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 36:11-12, s. 823-8
-
Tidskriftsartikel (refereegranskat)abstract
- Our objective was to study the effect of lopinavir/ritonavir on cerebrospinal fluid (CSF) viral load as part of an antiretroviral combination treatment for HIV-1 infected individuals, and to determine the steady-state concentrations of lopinavir in CSF in relationship to plasma concentrations. Paired CSF and plasma samples from 12 antiretroviral-naïve HIV-1 infected patients starting combination therapy containing lopinavir/ritonavir were collected at baseline, and during treatment at a first follow-up at median 3.0 months (range 2.6-6.0 months), and at a second follow-up at median 12.1 months (range 6.0-16.5 months). Levels of HIV-1 RNA, CD4+ T-cell count, beta2-microglobulin, neopterin, and lopinavir concentration were analysed. In addition, CSF and plasma lopinavir concentrations in 4 patients already on combination therapy including lopinavir/ritonavir were analysed. Nine of 11 patients had undetectable viral load in CSF and 5/11 in plasma at the first follow-up. At the second follow-up 7/7 had undetectable viral load in CSF and 9/9 in plasma. Intrathecal immunoactivation, measured by neopterin and beta2-microglobulin, decreased significantly both in CSF and serum. The total CSF concentrations of lopinavir were of the same order of magnitude as the unbound concentrations in plasma. Lopinavir mean (+/-SD) concentrations were 42.1 (+/-31.5) nM in CSF and 52.7 (+/-25.2) nM unbound in plasma. We found that antiretroviral combination therapy including lopinavir/ritonavir substantially decreases the viral load, both in CSF and plasma, as well as the intrathecal immunoactivation, measured by beta2-microglobulin and neopterin. CSF concentrations of lopinavir were low, but probably sufficient to have a virological effect.
|
|
| 40. |
- Yilmaz, Aylin, 1974, et al.
(författare)
-
Cerebrospinal fluid viral loads reach less than 2 copies/ml in HIV-1-infected patients with effective antiretroviral therapy.
- 2006
-
Ingår i: Antiviral therapy. - 1359-6535. ; 11:7, s. 833-7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A low-grade persisting viraemia despite long-term treatment with highly active antiretroviral therapy (HAART) has previously been demonstrated in HIV-1-infected patients. Whether ongoing viral replication also could be detected in cerebrospinal fluid (CSF) in those circumstances has not been studied before. METHODS: Paired CSF and blood samples from 13 neurologically asymptomatic HIV-1-infected patients on stable HAART were analysed regarding HIV-1 RNA, by using a PCR assay with a detection limit of 2 copies/ml. RESULTS: All 13 patients had HIV-1 RNA < 2 copies/ml in CSF, compared with 8/13 in plasma. CONCLUSION: We could not demonstrate any persistent viral replication in the CSF of neurologically asymptomatic HIV-1-infected patients on effective HAART, rendering it unlikely that CSF acts as a viral reservoir in this category of patients.
|
|
| 41. |
- Yilmaz, Aylin, 1974, et al.
(författare)
-
Treatment Intensification Has no Effect on the HIV-1 Central Nervous System Infection in Patients on Suppressive Antiretroviral Therapy.
- 2010
-
Ingår i: Journal of acquired immune deficiency syndromes (1999). - 1944-7884. ; 55:5, s. 590-596
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: Antiretroviral treatment (ART) significantly reduces cerebrospinal fluid (CSF) HIV-1 RNA levels and residual viremia is less frequently found in CSF than in blood. However, persistent intrathecal immunoactivation is common, even after several years of ART. To investigate whether low-level CSF viremia and residual immunoactivation within the central nervous system (CNS) derive from ongoing local viral replication, we conducted a study of treatment intensification in patients on effective ART. METHODS:: Ten patients on ART with plasma HIV RNA <50 copies per milliliter for >18 months were included. Intensification was given for in total 8 weeks: 4 weeks with maraviroc or lopinavir/ritonavir (good CNS penetration), and 4 weeks with enfuvirtide (poor CNS penetration). Lumbar punctures were performed 4 weeks before, at intensification commencement, at switchover after 4 weeks, at the conclusion of, and 4 weeks after the intensification period. RESULTS:: No significant changes in HIV RNA, neopterin, β2-microglobulin, immunoglobulin G index, albumin ratio, and CD4 T-cell count were observed, either in CSF or blood, neither before, during, nor after the intensification periods. CONCLUSIONS:: ART intensification did not reduce residual CSF HIV RNA levels or intrathecal immunoactivation in patients on ART. These findings do not support an ongoing viral replication in CNS.
|
|
