Current Issue : April - June Volume : 2015 Issue Number : 2 Articles : 8 Articles
A number of antiviral agents used against Human Immunodeficiency Virus (HIV) infection and hepatitis B virus\n(HBV) mono or co-infection have been associated with real nephrotoxicity (including tenofovir disoproxil fumarate\n(TDF), atazanavir, indinavir and lopinavir) or apparent changes in renal function (e.g. cobicistat, ritonavir, rilpivirine\nand dolutegravir). Patients with HIV are at higher risk of acute and chronic renal dysfunction, so baseline assessment\nand ongoing monitoring of renal function is an important part of routine management of patients with HIV.\nGiven the paucity of evidence in this area, we sought to establish a consensus view on how routine monitoring\ncould be performed in Australian patients on ART regimens, especially those involving TDF. A group of\nnephrologists and prescribers (an HIV physician and a hepatologist) were assembled by Gilead to discuss practical\nand reasonable renal management strategies for patients particularly those on TDF-based combination regimens\n(in the case of those with HIV-infection) or on TDF-monotherapy (in the case of HBV-mono infection). The group\nconsidered which investigations should be performed as part of routine practice, their frequency, and when\nspecialist renal referral is warranted. The algorithm presented suggests testing for serum creatinine along with\nplasma phosphate and an assessment of urinary protein (rather than albumin) and glucose.\nHere we advocate baseline tests of renal function at initiation of therapy. If creatinine excretion inhibitors (e.g.\ncobicistat or rilpivirine) are used as part of the ART regimen, we suggest creatinine is rechecked at 4 weeks and this\nvalue used as the new baseline. Repeat testing is suggested at 3-monthly intervals for a year and then at least yearly\nthereafter if no abnormalities are detected. In patients with abnormal baseline results, renal function assessment\nshould be performed at least 6 monthly. In HBV mono-infected patients advocate that a similar testing protocol\nmay be logical....
We report a 57-year old man with diabetes mellitus and hypertension who presented with acute HIV infection. Routine\nblood tests showed an elevated blood urea nitrogen and creatinine. Renal biopsy showed acute tubular nephropathy,\nwhich has not been reported to occur during acute HIV infection, in the absence of rhabdomyolysis or multiple organ\nsystem failure. Antiretroviral therapy was initiated. His renal failure gradually resolved without further intervention. At\none year of follow-up his HIV RNA was undetectable, and his renal function was normal. The case illustrates a rare\nmanifestation of acute HIV infection ââ?¬â?? acute renal failure - in an older man with diabetes and hypertension. In this\nsetting acute kidney injury might mistakenly have been attributed to his chronic comorbidities, and this case supports\nearly HIV-1 testing in the setting of a high index of suspicion....
Background: While Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need,\nthe epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income\ncountry has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine\nthe socio-demographic, behavioral, clinical and structural factors associated with virologic suppression.\nMethods: Virologic suppression on first-line ART at 6, 12, and 24 months from start of ART was defined as having a\nviral load measurement ?400 copies/mL without drug class modification and/or discontinuation. Drug class modification\nand/or discontinuation were defined based on the class of a particular drug. Quasi-Poisson regression was used\nto quantify the association of factors with virologic suppression.\nResults: From January 2000 through June 2010, 1311 patients started first-line ART; 987 (75%) patients used\nNNRTI-based regimens. Virologic suppression was achieved by 77%, 76% and 68% of patients at 6, 12 and\n24 months, respectively. Factors associated with virologic suppression at 12 months were: >8 years of formal\neducation (compared to <4 years, risk ratio (RR) 1.13, 95% confidence interval (95% CI) 1.03-1.24), starting ART\nin 2005-2010 (compared to 2000-2004, RR 1.25 95% CI 1.15-1.35), and clinical trial participation (compared to\nno participation, RR 1.08 95% CI 1.01-1.16). Also at 12 months, women showed less virologic suppression\ncompared to heterosexual men (RR 0.90 95% CI 0.82-0.99). For the 24-month endpoint, in addition to higher\neducation, starting ART in the later period, and clinical trial participation, older age and an NNRTI-based\nregimen were also independently associated with virologic suppression.\nConclusions: Our results show that in Brazil, a middle-income country with free access to treatment, over\nthree-quarters of patients receiving routine care reached virologic suppression on first-line ART by the end of\nthe first year. Higher education, more recent ART initiation and clinical trial participation were associated with\nimproved outcomes both for the 12-month and the 24-month endpoints, suggesting that further studies are\nneeded to understand what aspects relating to these factors lead to higher virologic suppression....
Background: Ongoing HIV-1 replication in lymphoid cells is one explanation of the persistence of HIV-1 reservoirs\ndespite highly active antiretroviral therapy (cART). We tested the potential of cART intensification by Maraviroc plus\nRaltegravir to decrease proviral HIV-1 DNA levels in lymphoid cells during a randomized trial.\nPatients and methods: We randomly assigned for 48 weeks 22 patients to continue their current first line regimen\nof Truvada�® plus Kaletra�® or intensify it with Maraviroc and Raltegravir. The primary objective was to obtain a 50%\ndecrease in proviral HIV-1 DNA levels in lymphoid cells with intensification. Blood samples were drawn at W-2, W0,\nW2, W4, W12, W24 and W48. Plasma viremia, cellular proviral DNA and cellular RNA, 2-LTR circles and lymphocytes\nsubsets were assayed using validated methods. Patients in the intensified group underwent a gut biopsy at baseline\nand W48 to measure proviral DNA levels. Statistical analysis used parametric and non-parametric tests.\nResults: Ten patients in each arm completed the trial. The 2 populations were comparable at baseline. No change\nin the reservoir size was observed in the intensified arm compared to the control arm measured in peripheral blood\nmononuclear cells (PBMCs). No change in the reservoir size was observed in gut proviral DNA in the intensified arm. In\nthis group, no increase in 2-LTR circles was observed as early as 2 weeks after intensification and no change was found\nin residual plasma RNA levels measured by the single copy assay. However, a decrease in CD8+ T cells activation was\nobserved at 24 and 48 weeks, as well as in PBMCs HIV-1 RNA levels.\nConclusion: We conclude that the intensification of a Protease Inhibitor regimen with Maraviroc and Raltegravir does\nnot impact the blood proviral DNA reservoir of HIV but can decrease the cell-associated HIV RNA, the CD8 activation\nand has a possible impact on rectal proviral HIV DNA in some patients....
Background: The CD5 protein antagonizes phosphorylation events downstream of T cell receptor (TCR) engagement\nto decrease T cell responsiveness. CD5-negative T cell clones respond preferentially over their CD5+ counterparts\nagainst cells with low human histocompatibility-linked leukocyte antigen (HLA) levels. In human immunodeficiency\nvirus type 1 (HIV-1) infection, CD5?CD8+ T cells increase in prevalence with disease progression.\nMethods: To investigate potential causes of this expansion of CD5?CD8+ T cells in HIV-1 infection, we compared CD5\nexpression on CD8+ T cells reactive against HIV-1 peptides, common viral peptides and a self peptide that together\nspan a broad range of TCR avidities in the context of the common HLA-A2 class I restriction molecule. Following\nstimulation, CD5 expression on peptide-specific CD8+ T cells was assessed by flow cytometry.\nResults: In healthy controls, there was no significant difference in the CD5+ percentage of CD8+ T cells specific for\ncommon viral peptides, but a lower percentage of those responding against a common self peptide expressed CD5.\nThe same relationship occurred in HIV-infected individuals, however, a lower percentage of HIV peptide-specific CD8+\nT cells than other viral peptide-specific CD8+ T cells expressed CD5. In terms of overall CD5 expression level at the\npeptide-specific responder population level, HIV-specific CD8+ T cells resembled those responsive against the self\npeptide, despite much higher avidity TCR/HLA/peptide interactions.\nConclusions: This deficit in CD5 expression selective for HIV-specific CD8+ T cells is consistent with in vivo adaptation\nto low avidity HIV peptide variants and has potential consequences for CD8+ T cell expansion, cross-reactivity and\nautoreactivity....
The 2014 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for\ninvestigators to hear the latest research developments in the clinical management of HIV and HCV infections as\nwell as HIV cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease\nprognosis and transformed this infection into a chronic disease. However, HIV is able to persist within the infected\nhost and the pandemic is still growing. The main 2014 ISHEID theme was, hence ââ?¬Å?Together for a world without\nHIV and AIDSââ?¬Â. In this report we not only give details on this main topic but also summarize what has been\ndiscussed in the areas of HCV coinfection and present a short summary on currently emerging viral diseases....
Background: Increasing numbers of HIV-infected patients in sub-Saharan Africa are exposed to antiretroviral\ntherapy (ART), but there are few data on lipid changes on first-line ART, and even fewer on second-line.\nMethods: DART was a randomized trial comparing monitoring strategies in Ugandan/Zimbabwean adults initiating\nfirst-line ART and switching to second-line at clinical/immunological failure. We evaluated fasting lipid profiles at\nsecond-line initiation and ?48 weeks subsequently in stored samples from Zimbabwean patients switching before\n18 September 2006.\nResults: Of 91 patients switched to second-line ART, 65(73%) had fasting samples at switch and ?48 weeks, 14(15%)\ndied or were lost <48 weeks, 10(11%) interrupted ART for >14 days and 2(2%) had no samples available. 56/65(86%)\nreceived ZDV/d4T + 3TC + TDF first-line, 6(9%) ZDV/d4T + 3TC + NVP and 3(5%) ZDV + 3TC with TDF and NVP.\nInitial second-line regimens were LPV/r + NNRTI in 27(41%), LPV/r + NNRTI + ddI in 33(50%) and LPV/r + TDF + ddI/\n3TC/ZDV in 6(9%). At second-line initiation median (IQR) TC, LDL-C, HDL-C and TG (mmol/L) were 3.3(2.8-4.0),\n1.7(1.3-2.2), 0.7(0.6-0.9) and 1.1(0.8-1.9) respectively. Levels were significantly increased 48 weeks later, by\nmean (SE) +2.0(0.1), +1.1(0.1), +0.5(0.05) and +0.4(0.2) respectively (p < 0.001; TG p = 0.01). 3% at switch vs 25%\n48 weeks later had TC >5.2 mmol/L; 3% vs 25% LDL-C >3.4 mmol/L and 91% vs 41% HDL-C <1.1 mmol/L (p < 0.001).\nSimilar proportions had TG >1.8 mmol/L (0 vs 3%) and TC/HDL-C ?5 (40% vs 33%) (p > 0.15).\nConclusion: Modest lipid elevations were observed in African patients on predominantly LPV/r + NNRTI-based\nsecond-line regimens. Routine lipid monitoring during second-line ART regimens may not be warranted in this\nsetting but individual cardiovascular risk assessment should guide practice....
Introduction: We report a case of an adult patient with human immunodeficiency virus (HIV), acute respiratory\ndistress syndrome (ARDS) and ventilator associated pneumonia (VAP) caused by multidrug resistant (MDR) bacteria\nthat was successfully managed with veno-venous extracorporeal membrane oxygenation (ECMO).\nCase report: A 25 year old male with no significant past medical history had been admitted to a local hospital due\nto dyspnea and fever. His pulmonary function subsequently failed necessitating mechanical ventilation (MV) and\nintroduction of ECMO support. The patient was transported for 300 km by road on ECMO to a tertiary medical\ncenter. The diagnosis of ARDS, HIV infection and MDR bacterial and fungal VAP was made. Patient was successfully\ntreated with antiretroviral therapy (ART), anti-infective agents and 58 days of veno-venous ECMO support, with\ncomplete resolution of the respiratory symptoms.\nConclusion: HIV infected patients with ARDS and MDR bacterial VAP whose HIV replication is controlled by ART\ncould be successfully managed with ECMO....
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