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Plasma Viral Load (plasma + viral_load)
Selected AbstractsORIGINAL ARTICLE: Analysis of Immunological Markers Associated with Pregnancy and HIV-1 Infection: Relevance in Perinatal Transmission in HIV-1-Infected Pregnant Women with Low Plasma Viral LoadAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2008Naresh Sachdeva Problem, In HIV-1-infected pregnant women with low plasma viral load, risk factors associated with perinatal HIV-1 transmission are not clearly understood. Method of study, We analyzed distribution of peripheral CD8 T-cell subsets, plasma cytokines and measured secretory leukocyte peptidase inhibitor (SLPI) and myeloid-related protein (MRP)-8 levels in whole-blood and cervico-vaginal fluid (CVF) specimens obtained from 35 HIV-1-infected pregnant women (group 1), 12 HIV-1-infected non-pregnant women (group 2) and 15 HIV-1 uninfected pregnant women (group 3). Results, The group 1 women had higher expression of CD38, human leukocyte antigen-DR and CD95 on CD8 T-cells and higher levels of plasma tumor necrosis factor-, and epidermal growth factor. CVF-SLPI levels were the highest in group-3, while MRP-8 levels were the highest in group 1 women in plasma and CVF (P < 0.01). Although there were no cases of perinatal HIV-1 transmission, group 1 women undergoing HIV-1-indicated cesarean section had lower levels of CVF-SLPI as compared with those undergoing normal vaginal delivery. Conclusion, Pregnancy contributes to the activation of peripheral CD8 T cells and increase in pro-inflammatory cytokines. Production of protective mucosal secretory factors such as SLPI is affected by HIV-1 infection in pregnant women and down-regulated SLPI levels may indirectly indicate a higher possibility of perinatal HIV-1 transmission. [source] Quantitation of reduced glutathione and cysteine in human immunodeficiency virus-infected patientsELECTROPHORESIS, Issue 10-11 2004Elena Sbrana Abstract Plasma viral load (VL) values and CD4+ cell count are employed clinically for initiation of therapy in the treatment of patients infected with human immunodeficiency virus (HIV), as previous clinical studies have shown a marked prevalence of acquired immunodeficiency sydrome (AIDS) development in seropositive individuals with VL values over 30,000 copies/mL. Many studies have shown that reduced glutathione (GSH) and cysteine (Cys) deficiency play an important role in the infection. We have developed capillary zone electrophoresis (CZE)-based assays and have used them to investigate the relationship between plasma and intracellular thiol levels and HIV-1 viremia in plasma. Blood samples from healthy volunteers and seropositive patients undergoing different antiretroviral regimes were analyzed in the study. The VL assay was based on CZE-UV detection of viral RNA at 260 nm. Determination of endogenous reduced Cys and GSH was achieved by CZE-UV detection of their mercurial complexes at 200 nm. We found that a decrease in GSH and Cys levels may be associated with disease progress. In fact, reduced GSH and Cys levels appear progressively reduced with increasing VL. [source] Frequent detection of cell-associated HIV-1 RNA in patients with plasma viral load <50 copies/mlJOURNAL OF MEDICAL VIROLOGY, Issue 10 2007Bernd Kupfer Abstract Despite prolonged undetectable plasma viral load some HIV-1 infected patients have been reported to develop resistance-associated mutations leading to treatment failure. The mechanisms for this phenomenon and the point of origin for residual viral evolution are still not elucidated. In order to quantify cell-associated HIV-1 RNA in patients with different levels of plasma viremia paired cell-associated HIV-1 RNA loads and plasma viral loads were determined. Weak inverse correlation between these parameters and the amounts of CD4+ T cells was observed, whereas there was no correlation between viral loads and CD8+ T cells or CD14+ monocytes, respectively. In a subset of patients, cell-associated and plasma HIV-1 env V3 sequences were analyzed. Plasma viral load and the amount of cell-associated HIV-RNA correlated strongly. However, in 62.3% of patients with undetectable plasma viral load cell-associated HIV-RNA could be detected. Analyses of HIV-RNA in plasma and blood cells showed identical sequences in 4/19 patients, whereas the majority of patients had differing HIV-1 RNA sequences in plasma and cells, respectively. In summary, this study shows that residual viral replication in peripheral blood still occurs in the majority of patients with undetectable plasma viral load. Since these replication events could lead to ongoing viral evolution it should be considered to optimize antiretroviral therapy in order to minimize the development of drug resistance. J. Med. Virol. 79:1440,1445, 2007. © Wiley-Liss, Inc. [source] Longitudinal follow up of SIVmac pathogenesis in rhesus macaques of Chinese origin: emergence of B cell lymphomaJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2002B. Ling Abstract: Two subspecies of rhesus (Rh) macaques, the Chinese (Ch) and Indian (Ind) subspecies were infected intravenously with 100TCID50 SIVmac239. CD4+, CD8+ T cells, plasma viral loads, depletion of intestinal lymphocytes with memory phenotype, humoral immune responses and clinical courses were monitored for 600 days. The pathogenesis of SIVmac was also compared with primary human immunodeficiency virus (HIV) infection of humans. Plasma viral loads in Ch Rh were lower in the acute and chronic phases compared with Ind Rh. SIVmac pathogenesis in Ch Rh was closer to virus loads in untreated HIV infected humans. Ch Rh had higher CD4/CD8 ratios, stronger antibody responses and interestingly, less depletion of intestinal memory CCR5+ CD4+ T lymphocytes compared with Ind Rh. One Ch Rh developed B cell origin lymphoma at 570 days post-infection, the first such report in this subspecies. Three of four Ind Rh developed AIDS within 6 months. The findings indicate that Ch Rh are more resistant to SIVmac pathogenesis compared with Ind Rh and that Ch Rh paralleled HIV-1 infections in untreated adult humans. The SIVmac infected Ch Rh subspecies are an acceptable model for HIV/AIDS. [source] Early neurodevelopmental markers predictive of mortality in infants infected with HIV-1DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2003Antolin Llorente PhD One-hundred and fifty-seven vertically infected HIV-1 positive infants (85 males, 72 females) underwent longitudinal assessment to determine whether early neurodevelopmental markers are useful predictors of mortality in those infants who survive to at least 4 months of age. Survival analysis methods were used to estimate time to death for quartiles of 4-month scores (baseline) on the Bayley Scales of Infant Development (BSID). Cox proportional hazards progression was used to estimate relative hazard (RH, 95% CI) of death for BSID scores and potential confounders. Thirty infants with BSID scores at 4 months of age died during follow-up. Survival analysis revealed greater mortality rates in infants with BSID (Mental Developmental Index and Psychomotor Developmental Index) scores in the lower quartile(p=0.004,p=0.036). Unadjusted univariate analyses revealed increased mortality associated with baseline CD4+ 29%, gestational age <37 weeks, smaller head circumference, advanced HIV and higher plasma viral load. BSID scores independently predicted mortality after adjusting for treatment, clinical category, gestational age, plasma viral load and CD4+ percentage. [source] Long-term assessment of nevirapine-containing highly active antiretroviral therapy in antiretroviral-naive HIV-infected patients: 3-year follow-up of the VIRGO studyHIV MEDICINE, Issue 7 2006V Reliquet Objectives Data on the durability of antiretroviral regimens over a 3-year period have only rarely been reported. The aim of this study was to evaluate the long-term efficacy and safety of one or two daily doses of nevirapine (NVP), in combination with stavudine (d4T) and didanosine (ddI), in HIV-infected patients. Methods This study was a follow-up of the VIR (amune) Grand Ouest (VIRGO) study, a 12-month open-label trial to assess the safety and immunovirological activity of NVP-d4T-ddI combination therapy in antiretroviral-naive HIV-1-infected adults with baseline CD4 counts ,200 cells/,L and plasma viral loads ,5000 HIV-1 RNA copies/mL. Of the 100 patients included in the study, the 67 patients remaining on the initial triple therapy at the end of the study (1 year) were offered an extra 24 months of follow-up. Results Of the 60 patients who extended follow-up, 46 were still being treated with d4T-ddI-NVP at month 36; 91% (39/43) had a plasma viral load <500 copies/mL (data were missing for three patients). CD4 cell counts increased over 36 months. Safety and tolerance were good with no unexpected long-term toxicity. Conclusion After 3 years of treatment with NVP-d4T-ddI, nearly half of the patients were still receiving the initial antiretroviral therapy with a sustained and durable immunovirological benefit. Long-term toxicity was mainly related to the nucleoside reverse transcriptase inhibitor components of the regimen. [source] Factors associated with virological response in HIV-infected patients failing antiretroviral therapy: a prospective cohort studyHIV MEDICINE, Issue 2 2005S Fournier Objectives To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy. Methods A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response. Results The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/,L. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8; P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9; P=0.006), of more than two new drugs (OR 3.0; P<0.0001), of abacavir (OR 1.9; P=0.03), or of lopinavir/ritonavir (OR 3.7; P=0.0002). Conclusions A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome. [source] TRIZAL study: switching from successful HAART to TrizivirTM (abacavir-lamivudine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence resultsHIV MEDICINE, Issue 2 2003C Katlama Objective To assess the antiviral efficacy, safety, and adherence in subjects who switched to TrizivirÔ following long-term HIV-1 RNA suppression. Study design A randomized, open-label, multicentre, 48-week comparative study in subjects who have received two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or an nonnucleoside reverse transcriptase inhibitor or three nucleoside reverse transcriptase inhibitors for at least 6 months, with a history of undetectable plasma HIV-1 RNA since initiation of therapy and plasma viral load of < 50 HIV-1 RNA copies/mL at screening. Methods Subjects were randomized 1:1 to continue their current treatment or to switch to a simplified treatment with TrizivirÔ administered twice daily. Assessments included plasma HIV-1 RNA, lymphocyte counts, clinical laboratory evaluations, adverse events, and adherence to treatment (obtained via subject self-report). Treatment failure was defined as a plasma viral load of , 400 HIV-1 RNA copies/mL on two consecutive occasions or premature discontinuation of randomized treatment. Results At week 48, the proportion of treatment failures in TrizivirÔ arm (23/106, 22%) was noninferior to that observed in continued arm (23/103, 22%) with a treatment difference stratified by prior ART of 1.2%[-10.1; 12.5]. Incidence of adverse events was similar in both treatment groups. The incidence of possible hypersensitivity reaction in the TrizivirÔ arm was 10%. Significant reductions in cholesterol and triglyceride plasma levels were observed in the TrizivirÔ arm (P < 0.001 and P = 0.006, respectively). Conclusion Switching to TrizivirÔ offers a potent and simplified regimen with equivalent efficacy and significant improvement in lipid abnormalities compared to continued triple therapy. [source] Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy, Bordeaux, France, 1998,1999HIV MEDICINE, Issue 3 2002F Bonnet Objectives To describe the causes of death in HIV-infected patients in the era of highly active antiretroviral therapy (HAART). Method A retrospective survey conducted in Bordeaux, France. Medical records of all deaths that had occurred in 1998 and 1999 amongst patients followed within the Aquitaine cohort were reviewed by the same physician. Immediate and underlying causes of death were described, taking into account the morbidity at the time of death. Results Sixty-six deaths occurred in 1998, and 41 in 1999. Sixty-seven per cent of deceased patients were male. Median age at time of death was 43 years (range 25,71), median CD4 was 162 cells/µL (0,957); 28% of patients had a CD4 count > 200 cells/µL and 7% plasma viral load < 500 HIV-RNA copies/mL. Amongst morbidity present at the time of death, there were 23 bacterial infections, 16 non-Hodgkin's lymphomas, 16 cirrhoses, 15 non HIV-related malignancies, 13 central nervous system diseases and 10 myocardiopathies. The main immediate causes of death were: multiple organ failure (21%), coma (18%), septic shock (15%) and acute respiratory failure (14%). Underlying causes of death were AIDS-defining events (48%), non AIDS HIV-related infection (3%), hepatitis B- or C-associated cirrhosis (14%), non HIV-related malignancies (11%), cardiovascular events (10%), suicide and overdose (6%), treatment-related fatalities (4%), injury (2%) and unknown (2%). Patients dying from AIDS-related events were more often female, had a lower CD4 count, a higher level of HIV-RNA, a shorter history of HIV infection and were less often coinfected with hepatitis B and C viruses than those dying from other underlying causes. Conclusions AIDS-related events are no longer the major causes of death of HIV-infected patients in the era of HAART. This evolving mortality pattern justifies an adaptation of both the epidemiological surveillance and the clinical monitoring of HIV-infected patients. [source] Quantitative evaluation of Enterocytozoon bieneusi infection in simian immunodeficiency virus-infected rhesus monkeysJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2003K. Sestak Abstract: The association of the microsporidia Enterocytozoon bieneusi with chronic diarrhea and wasting in individuals with acquired immunodeficiency syndrome (AIDS) has been demonstrated. The disease caused by E. bieneusi has been linked to decreased levels of circulating CD4+ T lymphocytes. In this study, we investigated the relationship between the extent of excretion of E. bieneusi in feces of simian immunodeficiency virus (SIV)-infected juvenile macaques and the CD4+ T lymphocyte counts in the peripheral blood. Twelve juvenile rhesus monkeys (Macaca mulatta) were intravenously inoculated with the pathogenic molecular clone SIVmac239. Numbers of CD4+ T lymphocytes were assessed by three-color flow cytometry. The presence of E. bieneusi DNA in feces was assessed by nested PCR. In addition, selected samples of feces were examined by competitive quantitative PCR to assess the level of E. bieneusi infection. Low (n = 5) to undetectable (n = 7) quantities of E. bieneusi were present in feces of the twelve animals in prior to inoculation with SIV. After SIV inoculation the number of animals shedding E. bieneusi increased (n = 10) as did the quantity of E. bieneusi shedding in the feces. Of the twelve juvenile animals, five animals died within 8 months post-SIV inoculation with symptoms of AIDS. Four of the five deceased animals showed shedding of E. bieneusi DNA in feces (,100 spores/g) for at least three consecutive months. Increased number of E. bieneusi in feces was accompanied by decreased counts of circulating CD4+ T lymphocytes and increased SIV plasma viral load. [source] A novel CD4-conjugated ultraviolet light-activated photocatalyst inactivates HIV-1 and SIV efficiently,JOURNAL OF MEDICAL VIROLOGY, Issue 8 2008Koushi Yamaguchi Abstract In this study, we found that the electric potential derived from the redox reaction of ultraviolet (UV)-illuminated CD4-conjugated titanium dioxide (TiO2) inactivated a wide range of high-titered primary HIV-1 isolates, regardless of virus co-receptor usage or genetic clade. In vitro incubation of HIV-1 isolates with CD4-conjugated TiO2 (CD4-TiO2) followed by UV illumination led to inhibition of viral infectivity in both H9 cells and peripheral blood mononuclear cells as well as to the complete inactivation of plasma virions from HIV-1-infected individuals. Treatment with a newly established extra-corporeal circulation system with the photocatalyst in rhesus macaques completely inactivated plasma virus in the system and effectively reduced the infectious plasma viral load. Furthermore, plasma viremia and infectious viral loads were controlled following a second therapeutic photocatalyst treatment during primary SIVmac239 infection of macaques. Our findings suggest that this therapeutic immunophysical strategy may help control human immunodeficiency viral infection in vivo. J. Med. Virol. 80:1322,1331, 2008. © 2008 Wiley-Liss, Inc. [source] Frequent detection of cell-associated HIV-1 RNA in patients with plasma viral load <50 copies/mlJOURNAL OF MEDICAL VIROLOGY, Issue 10 2007Bernd Kupfer Abstract Despite prolonged undetectable plasma viral load some HIV-1 infected patients have been reported to develop resistance-associated mutations leading to treatment failure. The mechanisms for this phenomenon and the point of origin for residual viral evolution are still not elucidated. In order to quantify cell-associated HIV-1 RNA in patients with different levels of plasma viremia paired cell-associated HIV-1 RNA loads and plasma viral loads were determined. Weak inverse correlation between these parameters and the amounts of CD4+ T cells was observed, whereas there was no correlation between viral loads and CD8+ T cells or CD14+ monocytes, respectively. In a subset of patients, cell-associated and plasma HIV-1 env V3 sequences were analyzed. Plasma viral load and the amount of cell-associated HIV-RNA correlated strongly. However, in 62.3% of patients with undetectable plasma viral load cell-associated HIV-RNA could be detected. Analyses of HIV-RNA in plasma and blood cells showed identical sequences in 4/19 patients, whereas the majority of patients had differing HIV-1 RNA sequences in plasma and cells, respectively. In summary, this study shows that residual viral replication in peripheral blood still occurs in the majority of patients with undetectable plasma viral load. Since these replication events could lead to ongoing viral evolution it should be considered to optimize antiretroviral therapy in order to minimize the development of drug resistance. J. Med. Virol. 79:1440,1445, 2007. © Wiley-Liss, Inc. [source] Cellular HIV-1 DNA quantitation in patients during simplification therapy with protease inhibitor-sparing regimensJOURNAL OF MEDICAL VIROLOGY, Issue 7 2007Loredana Sarmati Abstract Simplified regimens containing protease-inhibitors (PI)-sparing combinations were used in patients with virological suppression after prolonged highly active antiretroviral therapy. This study evaluated the total HIV-1 DNA quantitation as a predictor of long-term success for PI-sparing simplified therapy. Sixty-two patients were enrolled in a prospective non-randomized cohort. All patients have been receiving a triple-therapy regimen, two nucleoside reverse transcriptase inhibitors (NRTIs) plus one PI, for at least 9 months and were characterized by undetectable plasma HIV-1 RNA levels (<50 cp/ml) for at least 6 months. Patients were changed to a simplified PI-sparing regimen to overcome PI-associated adverse effects. HIV-DNA levels in peripheral blood mononuclear cells (PBMCs) were evaluated at baseline and at the end of follow-up. Patients with proviral DNA levels below the median value (226 copies/106 PBMCs) had a significant higher CD4 cell count at nadir (P,=,0.003) and at enrolment (P,=,0.001) with respect to patients with HIV-DNA levels above the median value. At month 18, 53 out of 62 (85%) patients on simplified regimen showed virological success, 4 (6.4%) patients experienced virological failure and 5 (8%) patients showed viral blip. At logistic regression analysis, HIV-DNA levels below 226 copies/106 PBMCs at baseline were associated independently to a reduced risk of virological failure or viral blip during simplified therapy (OR 0.002, 95% CI 0.001,0.46, P,=,0.025). The substitution of PI with NRTI or non-NRTIs may represent an effective treatment option. Indeed, treatment failure or viral blip were experienced by 6% and 8% of the patients on simplified therapy, respectively. In addition, sustained suppression of the plasma viral load was significantly correlated with low levels of proviral DNA before treatment simplification. J. Med. Virol. 79:880,886, 2007. © 2007 Wiley-Liss, Inc. [source] Lack of effect of chemokine receptor CCR2b gene polymorphism (64I) on HIV-1 plasma RNA viral load and immune activation among HIV-1 seropositive female workers in Abidjan, Côte d'IvoireJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001Christiane A. Adjé Abstract The prevalence of the CCR2b,V64I mutation among human immunodeficiency virus (HIV)-seropositive and -seronegative female workers and the potential effect of heterozygosity of this mutation on HIV-1 plasma RNA viral load and markers of immune activation were assessed. CCR2b,V64I was detected by polymerase chain reaction, followed by restriction enzymes analysis; plasma viral load was measured by the Amplicor HIV-1 monitor assay and CD4+ T-cell counts and markers of immune activation by standard three-color FACscan flow cytometry. Of the 260 female workers, 56 (21.5%) were heterozygous for CCR2b,V64I, and 8 (3%) were homozygous. Of the 99 HIV-seronegative female workers, 19 (19.2%) were heterozygous for the CCR2b,V64I mutation compared with 37 (23%) of the 161 HIV-seropositive FSW (P,=,0.47). In a univariate analysis of viral load among HIV-seropositive FSW, no difference was noted between those heterozygous for or without the mutation; both groups had plasma viral loads of 5.0 log10 copies/ml. After controlling for the effects of CD4+ T-cell counts in a multivariate analysis, no significant difference was observed between the groups in viral load or in markers of immune activation. The data suggest that the presence of the CCR2b mutation has no effect on HIV-1 plasma viral load and markers of immune activation in our study population. The finding that the frequency of this mutation is similar in HIV-seropositive and -seronegative female workers suggests that its presence is not associated with increased risk of HIV infection. J. Med. Virol. 64:398,401, 2001. © 2001 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Analysis of Immunological Markers Associated with Pregnancy and HIV-1 Infection: Relevance in Perinatal Transmission in HIV-1-Infected Pregnant Women with Low Plasma Viral LoadAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2008Naresh Sachdeva Problem, In HIV-1-infected pregnant women with low plasma viral load, risk factors associated with perinatal HIV-1 transmission are not clearly understood. Method of study, We analyzed distribution of peripheral CD8 T-cell subsets, plasma cytokines and measured secretory leukocyte peptidase inhibitor (SLPI) and myeloid-related protein (MRP)-8 levels in whole-blood and cervico-vaginal fluid (CVF) specimens obtained from 35 HIV-1-infected pregnant women (group 1), 12 HIV-1-infected non-pregnant women (group 2) and 15 HIV-1 uninfected pregnant women (group 3). Results, The group 1 women had higher expression of CD38, human leukocyte antigen-DR and CD95 on CD8 T-cells and higher levels of plasma tumor necrosis factor-, and epidermal growth factor. CVF-SLPI levels were the highest in group-3, while MRP-8 levels were the highest in group 1 women in plasma and CVF (P < 0.01). Although there were no cases of perinatal HIV-1 transmission, group 1 women undergoing HIV-1-indicated cesarean section had lower levels of CVF-SLPI as compared with those undergoing normal vaginal delivery. Conclusion, Pregnancy contributes to the activation of peripheral CD8 T cells and increase in pro-inflammatory cytokines. Production of protective mucosal secretory factors such as SLPI is affected by HIV-1 infection in pregnant women and down-regulated SLPI levels may indirectly indicate a higher possibility of perinatal HIV-1 transmission. [source] Safety and Efficacy of Raltegravir in HIV-Infected Transplant Patients Cotreated with Immunosuppressive DrugsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009L. Tricot Solid organ transplantations (SOT) are performed successfully in selected HIV-infected patients. However, multiple and reciprocal drug,drug interactions are observed between antiretroviral (ARV) drugs and calcineurin inhibitors (CNIs) through CYP450 metabolization. Raltegravir (RAL), a novel HIV-1 integrase inhibitor, is not a substrate of CYP450 enzymes. We retrospectively reviewed the outcomes of 13 HIV-infected transplant patients treated by an RAL + two nucleosidic reverse transcriptase inhibitor (NRTI) regimen, in terms of tolerability, ARV efficacy (plasma viral load, CD4 cell count), drug interactions, RAL pharmacokinetics and transplant outcome. Thirteen patients with liver (n = 8) or kidney (n = 5) transplantation were included. RAL was initiated (400 mg BID) either at time of transplantation (n = 6), or after transplantation (n = 7). Median RAL trough concentration was 507 ng/mL (176,890), which is above the in vitro IC95 for wild type HIV-1 strains (15 ng/mL). Target trough levels of CNIs were promptly obtained with standard dosages of tacrolimus or cyclosporine. RAL tolerability was excellent. There was no episode of acute rejection. HIV infection remained controlled. After a median follow-up of 9 months (range: 6,14), all patients were alive with satisfactory graft function. The use of an RAL + two NRTI-based regimen is a good alternative in HIV-infected patients undergoing SOT. [source] Long-term assessment of nevirapine-containing highly active antiretroviral therapy in antiretroviral-naive HIV-infected patients: 3-year follow-up of the VIRGO studyHIV MEDICINE, Issue 7 2006V Reliquet Objectives Data on the durability of antiretroviral regimens over a 3-year period have only rarely been reported. The aim of this study was to evaluate the long-term efficacy and safety of one or two daily doses of nevirapine (NVP), in combination with stavudine (d4T) and didanosine (ddI), in HIV-infected patients. Methods This study was a follow-up of the VIR (amune) Grand Ouest (VIRGO) study, a 12-month open-label trial to assess the safety and immunovirological activity of NVP-d4T-ddI combination therapy in antiretroviral-naive HIV-1-infected adults with baseline CD4 counts ,200 cells/,L and plasma viral loads ,5000 HIV-1 RNA copies/mL. Of the 100 patients included in the study, the 67 patients remaining on the initial triple therapy at the end of the study (1 year) were offered an extra 24 months of follow-up. Results Of the 60 patients who extended follow-up, 46 were still being treated with d4T-ddI-NVP at month 36; 91% (39/43) had a plasma viral load <500 copies/mL (data were missing for three patients). CD4 cell counts increased over 36 months. Safety and tolerance were good with no unexpected long-term toxicity. Conclusion After 3 years of treatment with NVP-d4T-ddI, nearly half of the patients were still receiving the initial antiretroviral therapy with a sustained and durable immunovirological benefit. Long-term toxicity was mainly related to the nucleoside reverse transcriptase inhibitor components of the regimen. [source] Longitudinal follow up of SIVmac pathogenesis in rhesus macaques of Chinese origin: emergence of B cell lymphomaJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2002B. Ling Abstract: Two subspecies of rhesus (Rh) macaques, the Chinese (Ch) and Indian (Ind) subspecies were infected intravenously with 100TCID50 SIVmac239. CD4+, CD8+ T cells, plasma viral loads, depletion of intestinal lymphocytes with memory phenotype, humoral immune responses and clinical courses were monitored for 600 days. The pathogenesis of SIVmac was also compared with primary human immunodeficiency virus (HIV) infection of humans. Plasma viral loads in Ch Rh were lower in the acute and chronic phases compared with Ind Rh. SIVmac pathogenesis in Ch Rh was closer to virus loads in untreated HIV infected humans. Ch Rh had higher CD4/CD8 ratios, stronger antibody responses and interestingly, less depletion of intestinal memory CCR5+ CD4+ T lymphocytes compared with Ind Rh. One Ch Rh developed B cell origin lymphoma at 570 days post-infection, the first such report in this subspecies. Three of four Ind Rh developed AIDS within 6 months. The findings indicate that Ch Rh are more resistant to SIVmac pathogenesis compared with Ind Rh and that Ch Rh paralleled HIV-1 infections in untreated adult humans. The SIVmac infected Ch Rh subspecies are an acceptable model for HIV/AIDS. [source] Chronic immune stimulation accelerates SIV-induced disease progressionJOURNAL OF MEDICAL PRIMATOLOGY, Issue 5 2001François Villinger The contribution of chronic immune stimulation on the progression of lentivirus-induced disease was evaluated in the SIVmac251 macaque model of AIDS. Following SIV inoculation, seroconversion and control of the acute viral replication phase, repeated immune stimulations with tetanus toxoid (TT), keyhole limpet hemocyanin (KLH) and allogeneic peripheral blood mononuclear cells (PBMC) were initiated in four monkeys. These animals showed a significant shortening of survival when compared with eight non-immune-stimulated control animals inoculated with the same route, dose and stock of SIVmac251 (median survival 9.5 months versus 17 months, P=0.010). In addition, when the comparison was extended to another 22 control animals of different origin but inoculated by the same route with similar doses and stocks of SIVmac251, the difference in survival was still significant (9.5 versus 18 months, P=0.003). This accelerated progression of symptomatic disease was not accompanied with significant increases in plasma viral loads, but suboptimal antibody responses to the immunizing antigens were noted, correlating with the length of survival. These findings may have implications for HIV-infected humans suffering from chronic infectious diseases. [source] Low-level plasma HIVs in patients on prolonged suppressive highly active antiretroviral therapy are produced mostly by cells other than CD4 T-cellsJOURNAL OF MEDICAL VIROLOGY, Issue 1 2009Gautam K. Sahu Abstract The cellular source(s) and the clinical significance of persistent low-level viremia, below 50 HIV RNA copies per ml of plasma, achieved in many patients with high adherence to highly active antiretroviral therapy (HAART) remain unclear. Also, it is not clear if residual plasma HIVs during HAART can become predominant populations in the rebounding plasma viral loads after therapy interruption. Since, different HIV quasispecies tend to compartmentalize in various cell types and tissue locations in patients during chronic infection, the phylogenetic relationships between HIV sequences amplified from residual plasma viruses and CD4 T cells of five patients on long-term suppressive therapy were examined. Three of these patients stopped therapy voluntarily for 3 weeks, but only one of them demonstrated viral load rebound in plasma. In phylogenetic analyses, the residual plasma viruses were found to be distinct genetically from the majority of CD4 T cell-associated virus populations in four of five patients. The compartmental analyses revealed that in all patients, plasma- and CD4 T cell-derived viral sequences were compartmentalized separately. Interestingly, the plasma sequences obtained before and after HAART-off in two patients were produced apparently from the same compartment, which was different from the circulating CD4 T cell-compartment. These results suggest the possibility that residual plasma viruses in patients on long-term suppressive HAART may be produced persistently from a cellular source yet to be identified, and are capable of spreading quickly in vivo, accounting for the rapid rebound of viral loads in plasma after therapy interruption. J. Med. Virol. 81:9,15, 2009. © 2008 Wiley-Liss, Inc. [source] Frequent detection of cell-associated HIV-1 RNA in patients with plasma viral load <50 copies/mlJOURNAL OF MEDICAL VIROLOGY, Issue 10 2007Bernd Kupfer Abstract Despite prolonged undetectable plasma viral load some HIV-1 infected patients have been reported to develop resistance-associated mutations leading to treatment failure. The mechanisms for this phenomenon and the point of origin for residual viral evolution are still not elucidated. In order to quantify cell-associated HIV-1 RNA in patients with different levels of plasma viremia paired cell-associated HIV-1 RNA loads and plasma viral loads were determined. Weak inverse correlation between these parameters and the amounts of CD4+ T cells was observed, whereas there was no correlation between viral loads and CD8+ T cells or CD14+ monocytes, respectively. In a subset of patients, cell-associated and plasma HIV-1 env V3 sequences were analyzed. Plasma viral load and the amount of cell-associated HIV-RNA correlated strongly. However, in 62.3% of patients with undetectable plasma viral load cell-associated HIV-RNA could be detected. Analyses of HIV-RNA in plasma and blood cells showed identical sequences in 4/19 patients, whereas the majority of patients had differing HIV-1 RNA sequences in plasma and cells, respectively. In summary, this study shows that residual viral replication in peripheral blood still occurs in the majority of patients with undetectable plasma viral load. Since these replication events could lead to ongoing viral evolution it should be considered to optimize antiretroviral therapy in order to minimize the development of drug resistance. J. Med. Virol. 79:1440,1445, 2007. © Wiley-Liss, Inc. [source] Lack of effect of chemokine receptor CCR2b gene polymorphism (64I) on HIV-1 plasma RNA viral load and immune activation among HIV-1 seropositive female workers in Abidjan, Côte d'IvoireJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001Christiane A. Adjé Abstract The prevalence of the CCR2b,V64I mutation among human immunodeficiency virus (HIV)-seropositive and -seronegative female workers and the potential effect of heterozygosity of this mutation on HIV-1 plasma RNA viral load and markers of immune activation were assessed. CCR2b,V64I was detected by polymerase chain reaction, followed by restriction enzymes analysis; plasma viral load was measured by the Amplicor HIV-1 monitor assay and CD4+ T-cell counts and markers of immune activation by standard three-color FACscan flow cytometry. Of the 260 female workers, 56 (21.5%) were heterozygous for CCR2b,V64I, and 8 (3%) were homozygous. Of the 99 HIV-seronegative female workers, 19 (19.2%) were heterozygous for the CCR2b,V64I mutation compared with 37 (23%) of the 161 HIV-seropositive FSW (P,=,0.47). In a univariate analysis of viral load among HIV-seropositive FSW, no difference was noted between those heterozygous for or without the mutation; both groups had plasma viral loads of 5.0 log10 copies/ml. After controlling for the effects of CD4+ T-cell counts in a multivariate analysis, no significant difference was observed between the groups in viral load or in markers of immune activation. The data suggest that the presence of the CCR2b mutation has no effect on HIV-1 plasma viral load and markers of immune activation in our study population. The finding that the frequency of this mutation is similar in HIV-seropositive and -seronegative female workers suggests that its presence is not associated with increased risk of HIV infection. J. Med. Virol. 64:398,401, 2001. © 2001 Wiley-Liss, Inc. [source] Human immunodeficiency virus (HIV)-specific T helper responses fail to predict CD4+ T cell decline following short-course treatment at primary HIV-1 infectionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008J. Fox Summary Early anti-retroviral treatment (ART) in primary human immunodeficiency virus (HIV) infection (PHI) may have unique, restorative immunological and virological benefits which could enhance clinical outcomes. However, the sustainability of these HIV-specific immune responses and their impact on clinical outcome remains unclear. We present a 3-year longitudinal clinical and immunological follow-up of a single-arm, prospective study assessing the long-term impact of a short-course of ART (SCART) during PHI. Twenty-eight subjects with defined PHI received 3 months of SCART at HIV-1 seroconversion. HIV-specific interferon-,+ CD4+ T cell responses, CD4 cell counts and plasma viral loads were assessed prospectively. Clinical outcome was defined as the time taken from PHI to a fall in CD4 cell counts <350 cells/,l on two or more occasions. Of 28 patients, 25 (89%) had detectable HIV-specific CD4+ helper responses at baseline. Five of 11 (45%) patients had preserved HIV-specific CD4+ responses 3 years after stopping SCART. Neither the presence nor magnitude of HIV-1-specific T helper responses either at baseline or 3 years following SCART cessation predicted clinical outcome. Rebound viraemia associated with stopping SCART did not diminish HIV-1-specific CD4+ responses. Long-term (>3 years) preservation of virus-specific CD4+ cells occurred in 45% of patients receiving SCART in PHI. There was no correlation between either the presence or magnitude of these responses and clinical outcome. [source] | |||||||||||||||||||||||||