Current Issue : July - September Volume : 2015 Issue Number : 3 Articles : 9 Articles
Background: Antiretroviral treatment (ART) has been effective in reducing HIV/AIDS related morbidity and\nmortality. However, the use and uptake of ART has resulted in adverse reactions, due mainly to the medicineââ?¬â?¢s\ntoxicity and interactions with other medicines. The timing of adverse drug reactions (ADRs) among these patients is\na critical public health issue for antiretroviral (ARV) treatment adherence and retention. Reliable monitoring of HIV\npatients on ART is through a structured pharmacovigilance surveillance system. However, recurrent nature of these\ndata pose challenges in their analyses. This study aimed at modelling the timing of ADR events in HIV patients on\nART using correlated time-to-event models.\nMethods: The data concern 590 HIV patients registered onto the Medunsa National ARV Pharmacovigilance\nSurveillance System within 6 months of ART initiation between February 2007 and July 2011. Recurrent times of\nADRs and baseline characteristics: patient gender, and age, ART regimen, clinic and initiation period were extracted\nfrom the data. The recurrent ADR events data were modelled using both shared frailty and marginal models on\nthe five patientsââ?¬â?¢ characteristics as covariates.\nResults: Out of 590 patients, 67% were female, 68% started on regimen: Stavudine, Lamivudine and Efavirenz; 37% had\nexperienced at least one ADR and 67% started ART in 2009ââ?¬â??2011. Age (p-value = 0.0210), clinic (p-value < 0.0001) and\nperiod of ART initiation (p-value = 0.0002) were significantly associated with timing of first ADR. There was a significantly\nhigher rates of ADR recurrences in patients aged 38ââ?¬â??44 years [HR = 2.45; 95% CI = (1.47; 4.10)] vs. 30 years and less,\npatients taking regimen: Zidovudine, Lamivudine and Nevarapine) vs. regimen: Stavudine, Lamivudine and Efavirenz\n[HR = 2.09; 95% CI = (1.35; 3.22)], while the rate was lower among those who started ART in 2009ââ?¬â??2011 vs. those who\ninitiated in 2007ââ?¬â??2008 [HR = 0.55; 95% CI = (0.40; 0.76)].\nConclusion: More realistic time-to-event models for recurrent events data have been used to analyse timing of ADR\nevents in HIV patients taking ARV treatment. Age, antiretroviral regimen type and period of initiation of ART were\nassociated with the timing of HIV/AIDS drug related adverse reactions regardless of the analysis model used. This study\nhas public health policy implications in addressing the added morbidity among HIV patients taking ARV treatment in the\ncontext of universal scaling up of ARV treatment....
Background: Treatments in patients with multidrug resistance often involve the use of multiple agents with\npartial antiviral activity and overlapping metabolic toxicities. Enfuvirtide is therefore a welcome addition to the\nantiretroviral management of patients with multiclass resistant virus, given the low risk of systemic toxicities and\nnovel mechanism of action relative to existing drug classes.\nThe aim of this study was to evaluate the effectiveness of ENF plus optimized background regimen (OBR) in a\nMexican cohort of highly HIV-1 ARV-experienced patients.\nMethods: Prospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started\ntherapy with an ENF-containing regimen. The effectiveness of ENF treatment was evaluated with percentages of\nundetectable HIV-1 RNA viral load after 24 and 48 weeks of treatment, and changes in CD4+ cell counts.\nResults: Forty patients >18 years were included. After 24 weeks of treatment, 91% of patients had HIV-1 RNA viral\nload <400 copies/mL and 65.8% had <50 copies/mL. At week 48 of treatment, 81.4% of the patients had HIV-1 RNA\n<400 copies/mL and 55.5% had <50 copies/mL; in both cases p <0.0001 compared to baseline. Increase CD4+ cells\nwere also statistically significant at weeks 24 and 48 with respect to the baseline. Pain at the site of injection was\nthe main adverse event in 100% of patients.\nConclusion: Our study provides clinically important evidence of the effectiveness and safety of ENF in highly\nARV-experienced HIV-1-infected patients. These findings strengthen the results of previous randomized controlled\ntrials with this agent....
Background: The Human Immune Deficiency Virus (HIV) can manifest neurologically in both adults and children. Early\ninvasion of the central nervous system by the virus, affecting the developing brain, is believed to result in the most\ncommon primary HIV-related neurological complication, HIV Encephalopathy (HIVE). In countries such as South Africa\nwhere many children have not been initiated on antiretroviral treatment early, HIVE remains a significant clinical problem.\nMethods: Children were selected from a clinic for children with neurologic complications of HIV, located at the Red Cross\nWar Memorial Childrenââ?¬â?¢s Hospital, South Africa 2008ââ?¬â??2012. Eligible subjects fulfilled the following inclusion criteria: aged 6\nmonths-13 years; positive diagnosis of HIV infection, vertically infected and HIVE as defined by CDC criteria. Each\nparticipant was prospectively assessed by a Pediatric Neurologist using a standardized proforma which collated relevant\ndetails of background, clinical and immunological status.\nResults: The median age of the 87 children was 64 months (interquartile range 27ââ?¬â??95 months). All except one child\nwere on anti retroviral treatment, 45% had commenced treatment <12 months of age. Delayed early motor milestones\nwere reported in 80% and delayed early speech in 75% of children in whom we had the information. Twenty percent\nhad a history of one or more seizures and 41% had a history of behavior problems. Forty-eight percent had microcephaly\nand 63% a spastic diplegia. CD4 percentages followed a normal distribution with mean of 30.3% (SD 8.69). Viral loads\nwere undetectable ( Read More
Background: The emergence of transmitted drug resistance (TDR) compromises the effect of antiretroviral therapy\n(ART), resulting in treatment failure of human immunodeficiency virus (HIV) disease. Although more than a decade\nhas passed since ART was introduced into Indonesia, information on TDR is limited. Here, a genotypic study of TDR\namong ART-na�¯ve individuals was conducted in Surabaya, Indonesia.\nMethod: HIV-1 seropositive participants were recruited from the communities of commercial sex workers and\nintravenous drug users as well as from the university teaching hospital in Surabaya. Protease (PR) and reverse\ntranscriptase (RT) genes were sequenced in order to conduct HIV-1 subtyping and phylogenetic analysis and to\ndetect TDR. TDR was defined as the presence of at least one surveillance drug resistance mutation on the WHO list\nor major drug resistance mutations in the International AIDS Society-USA panel.\nResult: Fifty two and 47 of the PR and RT genes, respectively, were successfully sequenced in the 58 samples. HIV-1\nsubtyping revealed that 86.3% (50/58) of the sequenced samples were classified as CRF01_AE, 8.6% as subtype B,\n3.4% as B/CRF01_AE, and 1.7% as A/G/CRF01_AE. TDR of PR inhibitors was not detected in this study. In contrast,\nTDR of RT inhibitors was detected in 4.3% (2/47) of samples. In addition, minor drug resistance mutations were\ndetected in 98.1% (51/52) and 12.8% (6/47) of PR and RT genes, respectively.\nConclusion: This study clarified the predominance of the CRF01_AE strain in Surabaya, Indonesia. The prevalence of\nTDR was below 5%, indicating that the currently available first-line regimen is still effective in Surabaya. However,\nthe prevalence might be underestimated since we detected only major population of HIV-1 in individuals.\nTherefore, continuous surveillance is required in order to detect the emergence of TDR in the early phase....
Aims: HIV infection may be associated with an increased recurrence rate of myocardial infarction. Our aim was to\ndetermine whether HIV infection is a risk factor for worse outcomes in patients with coronaray artery disease.\nMethods: We compared data aggregated from two ongoing cohorts: (i) the Acute Myocardial Infarction in Switzerland\n(AMIS) registry, which includes patients with acute myocardial infarction (AMI), and (ii) the Swiss HIV Cohort Study (SHCS),\na prospective registry of HIV-positive (HIV+) patients. We included all patients who survived an incident AMI occurring on\nor after 1st January 2005. Our primary outcome measure was all-cause mortality at one year; secondary outcomes included\nAMI recurrence and cardiovascular-related hospitalisations. Comparisons used Cox and logistic regression analyses, respectively.\nResults: There were 133 HIV+, (SHCS) and 5,328 HIV-negative [HIV-] (AMIS) individuals with incident AMI. In the SHCS\nand AMIS registries, patients were predominantly male (72% and 85% male, respectively), with a median age of 51 years\n(interquartile range [IQR] 46ââ?¬â??57) and 64 years (IQR 55ââ?¬â??74), respectively. Nearly all (90%) of HIV+ individuals were on\nsuccessful antiretroviral therapy. During the first year of follow-up, 5 (3.6%) HIV+ and 135 (2.5%) HIV- individuals died. At\none year, HIV+ status after adjustment for age, sex, calendar year of AMI, smoking status, hypertension and\ndiabetes was associated with a higher risk of death (HR 4.42, 95% CI 1.73-11.27). There were no significant\ndifferences in recurrent AMIs (4 [3.0%] HIV+ and 146 [3.0%] HIV- individuals, OR 1.16, 95% CI 0.41-3.27) or in\nhospitalization rates (OR 0.68 [95% CI 0.42-1.11]).\nConclusions: HIV infection was associated with a significantly increased risk of all-cause mortality one year after\nincident AMI....
Background: Antimalarials quinacrine (Qc) and chloroquine (Cq) intercalate DNA, potentiate the activity of other\ndrugs and have lysosomotropic, anti-inflammatory and antiviral activities that could increase the effect of the\n3?-azido-3?-deoxythymidine (AZT) antiretroviral agent. The aim of the current study was to evaluate if Qc and Cq\ncould improve the in vitro effect of the antiretroviral AZT agent.\nFindings: Inhibition of viral replication in human immunodeficiency virus (HIV)SF33-infected peripheral blood\nmononuclear cells treated with Qc or Cq, alone or combined with a low dose of AZT was measured. Viral\nreplication increased with Qc and decreased with high doses of Cq. The increase of replication caused by Qc was\nreversed by AZT. Neither Qc nor Cq significantly changed the antiviral activity of AZT.\nConclusion: Cq does not potentiate the effect of AZT, but it is effective by itself at high doses. The rise of HIV\nreplication by Qc could be deleterious in HIV endemic regions, where it is used as antimalarial. The mechanisms\nassociated to this phenomenon must be identified....
Background: While HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor\nbased cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily\nin situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced\nUridine-5�-diphosph- gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to\nincreased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part\nof cost-saving effects in countries with high-tuberculosis prevalence and less economic power.\nMethods: We report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from\ndisseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were\nmeasured with HPLC (internal standard: carbamazepine, LLQ 11 ng/ml, validation with Valistat 2.0 program\n(Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used.\nResults: High intra-personal variability in raltegravir serum levels was seen. Comparable Cmax concentrations were\nfound for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While Cmax\nseems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased AUC12\nis clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease\nin serum levels.\nConclusions: We found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co-medication leads\nto optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations...
Background: Tubular dysfunction is common in HIV-infected people and detection of proteinuria is essential to\nidentify this problem. In low-income countries, resources for detection of proteinuria using the Kidney Disease\nImprove Global Outcomes (KDIGO) gold standard urinary protein/creatinine ratio (uPCR) is rarely possible, and\nuse of the protein reagent strip (PRS) could be an option in these places. The aims of this study were to establish\nthe concordance between PRS and uPCR to detect tubular proteinuria in HIV-infected people, and to assess the\nsensitivity and specificity of PRS as a diagnostic method in this group.\nMethods: A cross-sectional study was conducted to evaluate the correlation between the two techniques to detect\nprotein in urine. Participants were enrolled for a period of 6 months. The measurements were performed in participants\nwho were on highly active antiretroviral therapy (HAART) or prior to the start of treatment. Proteinuria was defined as\nuPCR ? 150 mg/g, and/or ? trace on PRS. A phi coefficient was calculated to establish the degree of correlation. We\nassessed the sensitivity and specificity of PRS compared with uPCR using standard methods.\nResults: A total of 799 subjects were included. Of these, 737 (92%) were men. The mean age was 32.9 years\n(Ã?±10.1 years). Most (561, 70%) were on antiretroviral treatment. The mean estimated glomerular filtration rate (eGFR)\ncalculated according to Modification of Diet in Renal Disease (MDRD)-4 was 113.0 mL/min (Ã?±22.6). Comorbidities\nincluded diabetes mellitus (10, 1.3%) and hypertension (17, 2.1%). The prevalence of proteinuria detected by PRS was\n8.3% (n = 66) and by uPCR 10.6% (n = 85). The concordance assessed by phi correlation coefficient was 0.70, p < 0.001,\nwith a sensitivity of 51.7% (95% confidence interval [CI] 41%ââ?¬â??62%) and specificity 97% (95% CI 39%ââ?¬â??97%).\nConclusions: There is a high concordance between detection of proteinuria by PRS and uPCR. Therefore, in\nlow-income countries PRS can be helpful for detecting tubular damage in people infected with HIV....
Background: The availability of HIV antiretroviral therapy (ART) has been associated with the development of\ntransmitted drug resistance-associated mutations (TDRM). TDRM can compromise treatment effectiveness in patients\ninitiating ART and the prevalence can vary in different clinical settings. In this study, we investigated the proportion\nof TDRM in treatment-naÃ?¯ve, recently infected HIV-positive individuals sampled from four urban locations across Asia\nbetween 2007ââ?¬â??2010.\nMethods: Patients enrolled in the TREAT Asia Studies to Evaluate Resistance ââ?¬â?? Surveillance Study (TASER-S) were\ngenotyped prior to ART initiation, with resulting resistance mutations analysed according to the WHO 2009 list.\nResults: Proportions of TDRM from recently infected individuals from TASER-S ranged from 0% to 8.7% - Hong Kong:\n3/88 (3.4%, 95% CI (0.71%-9.64%)); Thailand: Bangkok: 13/277 (4.7%, 95% CI (2.5%-7.9%)), Chiang Mai: 0/17 (0%, 97.5% CI\n(0%-19.5%)); and the Philippines: 6/69 (8.7%, 95% CI (3.3%-18.0%)). There was no significant increase in TDRM over time\nacross all four clinical settings.\nConclusions: The observed proportion of TDRM in TASER-S patients from Hong Kong, Thailand and the Philippines\nwas low to moderate during the study period. Regular monitoring of TDRM should be encouraged, especially with the\nscale-up of ART at higher CD4 levels....
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