Evaluation of a pharmacogenetic test in Thailand for abacavir hypersensitivity screening in human immunodeficiency virus infection
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ABSTRACT:
SUBMITTER: Chonlaphat S
PROVIDER: S-EPMC4127989 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundAbacavir is a nucleoside reverse transcriptase inhibitor that is used as a component of the antiretroviral treatment regimen in the management of the human immunodeficiency virus for both adults and children. It is efficacious, but its use may be limited by a hypersensitivity reaction linked with the HLA-B*57:01 genotype. HLA-B*57:01 has been reported to be rare in African populations. Because of the nature of its presentation, abacavir hypersensitivity is prone to late diagnosis and treatment, especially in settings where HLA-B*57:01 genotyping is not routinely done.Case reportWe report a case of a severe hypersensitivity reaction in a 44-year-old Kenyan female living with the human immunodeficiency virus and on abacavir-containing antiretroviral therapy. The patient presented to the hospital after recurrent treatment for a throat infection with complaints of fever, headache, throat ache, vomiting, and a generalized rash. Laboratory results evidenced raised aminotransferases, for which she was advised to stop the antiretrovirals that she had recently been started on. The regimen consisted of abacavir, lamivudine, and dolutegravir. She responded well to treatment but was readmitted a day after discharge with vomiting, severe abdominal pains, diarrhea, and hypotension. Her symptoms disappeared upon admission, but she was readmitted again a few hours after discharge in a hysterical state with burning chest pain and chills. Suspecting abacavir hypersensitivity, upon interrogation she reported that she had taken the abacavir-containing antiretrovirals shortly before she was taken ill. A sample for HLA-B*57:01 was taken and tested positive. Her antiretroviral regimen was substituted to tenofovir, lamivudine, and dolutegravir, and on subsequent follow-up she has been well.ConclusionsClinicians should always be cognizant of this adverse reaction whenever they initiate an abacavir-containing therapy. We would recommend that studies be done in our setting to verify the prevalence of HLA-B*57:01.
| S-EPMC9641955 | biostudies-literature
Project description:The objectives of this study were to assess the prevalence and factors associated with hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected and -uninfected Thai pregnant women and the rate of HCV transmission to their infants.Study subjects included 1435 HIV-infected pregnant women and their infants, enrolled in a perinatal HIV prevention trial, and a control group of 448 HIV-uninfected pregnant women. Women were screened for HCV antibodies with an enzyme immunoassay. Positive results were confirmed by recombinant immunoblot and HCV RNA quantification. Infants were tested for HCV antibodies at 18 months or for HCV RNA at between 6 weeks and 6 months.Of the HIV-infected women, 2.9% were HCV-infected compared to 0.5% of HIV-uninfected women (p=0.001). Only history of intravenous drug use was associated with HCV infection in HIV-infected women. Ten percent of infants born to co-infected mothers acquired HCV. The risk of transmission was associated with a high maternal HCV RNA (p=0.012), but not with HIV-1 load or CD4 count.Acquisition of HCV through intravenous drug use partially explains the higher rate of HCV infection in HIV-infected Thai women than in HIV-uninfected controls. Perinatal transmission occurred in 10% of infants of HIV-HCV-co-infected mothers and was associated with high maternal HCV RNA.
| S-EPMC2886172 | biostudies-literature
Project description:Infections with feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) occur worldwide and are among the most important infectious diseases in cats. The aim of the present study was to determine the prevalence of FIV and FeLV infection in healthy outdoor cats in North, Northeast and Central Thailand. So far, a study on retrovirus prevalence of healthy cats in Thailand in a larger geographic area has not been published yet. In addition, risk factors for FIV and FeLV infections were evaluated. Two hundred sixty healthy cats were prospectively recruited. They originated from 13 locations in North, Northeast, and Central Thailand and were presented for either preventive health care and/or neutering. In each cat, a physical examination was performed to confirm health status. FIV and FeLV status was determined using a commercial rapid enzyme-linked immunosorbent assay (ELISA) (SNAP Combo Plus FeLV/FIV, IDEXX). Risk factors were analyzed by binary logistic regression analysis. Samples of 15/260 (5.8%) cats were positive for FIV antibodies, and 11/260 (4.2%) samples were positive for FeLV antigen. One of the 260 (0.4%) cats was positive for both, FIV and FeLV infection. In binary logistic regression analysis, no parameter was associated with a higher risk for FeLV infection. However, cats had a significantly (p = 0.025) higher risk for FIV infection when they were 2 years or older. FIV and FeLV infections occur in healthy cats in North, Northeast and Central Thailand, but prevalence was lower than expected. No risk factors for FeLV infection were detected, but risk for FIV infection increases with age.
| S-EPMC8862143 | biostudies-literature
Project description:Abacavir is an antiretroviral drug used to reduce human immunodeficiency virus (HIV) replication and decrease the risk of developing acquired immune deficiency syndrome (AIDS). However, its therapeutic value is diminished by the fact that it is associated with drug hypersensitivity reactions in up to 8% of treated patients. This hypersensitivity is strongly associated with patients carrying human leukocyte antigen (HLA)-B*57:01, but not patients carrying closely related alleles. Abacavir's specificity to HLA-B*57:01 is attributed to its binding site within the peptide-binding cleft and subsequent influence of the repertoire of peptides that can bind HLA-B*57:01. To further our understanding of abacavir-induced hypersensitivity we used molecular dynamics (MD) to analyze the dynamics of three different peptides bound to HLA-B*57:01 in the presence and absence of abacavir or abacavir analogues. We found that abacavir and associated peptides bind to HLA-B*57:01 in a highly diverse range of conformations that are not apparent from static crystallographic snapshots, but observed no difference in either the conformations, nor degree of flexibility when compared to abacavir-unbound systems. Our results support hypersensitivity models in which abacavir-binding alters the conformational ensemble of neopeptides, so as to favour exposed peptide surfaces that are no longer recognized as self by circulating CD8+ T cells, and are conducive to TCR binding. Our findings highlight the need to also consider the role of dynamics in understanding drug-induced hypersensitivities at the molecular and mechanistic level. This additional insight can help inform the chemical modification of abacavir to prevent hypersensitivity reactions in HLA-B*57:01+ HIV patients whilst retaining potent antiretroviral activity.
| S-EPMC6642150 | biostudies-literature
Project description:Abacavir is a nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy in HIV-1-infected patients. Because this drug can cause a hypersensitivity reaction that is correlated with the presence of the HLA-B*57:01 allotype, screening for the presence of HLA-B*57:01 is recommended before abacavir initiation. Different genetic assays have been developed for HLA-B*57:01 screening, each with specific sensitivity, turnaround time and assay costs. Here, a new real-time PCR (qPCR) based analysis is described and compared to sequence specific primer PCR with capillary electrophoresis (SSP PCR CE) on 149 patient-derived samples, using sequence specific oligonucleotide hybridization combined with high resolution SSP PCR as gold standard. In addition to these PCR based methods, a complementary approach was developed using flow cytometry with an HLA-B17 specific monoclonal antibody as a pre-screening assay to diminish the number of samples for genetic testing. All three assays had a maximum sensitivity of >99. However, differences in specificity were recorded, i.e. 84.3%, 97.2% and >99% for flow cytometry, qPCR and SSP PCR CE respectively. Our data indicate that the most specific and sensitive of the compared methods is the SSP PCR CE. Flow cytometry pre-screening can substantially decrease the number of genetic tests for HLA-B*57:01 typing in a clinical setting.
| S-EPMC4398410 | biostudies-literature
Project description:Recent studies have shown the public health importance of identifying individuals with acute human immunodeficiency virus infection (AHI); however, the cost of nucleic acid amplification testing (NAAT) makes individual testing of at-risk individuals prohibitively expensive in many settings. Pooled NAAT (or group testing) can improve efficiency and test performance of testing for AHI, but optimizing the pooling algorithm can be difficult. We developed simple, flexible biostatistical models of specimen pooling with NAAT for the identification of AHI cases; these models incorporate group testing theory, operating characteristics of biological assays, and a model of viral dynamics during AHI. Pooling algorithm sensitivity, efficiency (test kits used per individual specimen evaluated), and positive predictive value (PPV) were modeled and compared for three simple pooling algorithms: two-stage minipools (D2), three-stage hierarchical pools (D3), and square arrays with master pools (A2m). We confirmed the results by stochastic simulation and produced reference tables and a Web calculator to facilitate pooling by investigators without specific biostatistical expertise. All three pooling strategies demonstrated improved efficiency and PPV for AHI case detection compared to individual NAAT. D3 and A2m algorithms generally provided better efficiency and PPV than D2; additionally, A2m generally exhibited better PPV than D3. Used selectively and carefully, the simple models developed here can guide the selection of a pooling algorithm for the detection of AHI cases in a wide variety of settings.
| S-EPMC2395100 | biostudies-literature
Project description:Strongyloides stercoralis affects more than half a billion people worldwide, and hyperinfection in immunocompromised patients can be fatal. Elimination of this neglected tropical disease requires field-applicable diagnostic tools. We conducted a laboratory evaluation of a lateral flow rapid dipstick test (SsRapid™) using sera samples from a Strongyloides-endemic area in northeast Thailand. Group 1 was S. stercoralis-positive and larvae- and/or antibody-positive (according to the IgG ELISA) (N = 100). Group 2 had negative fecal examination and IgG ELISA results (N = 25). Group 3 had other parasitic infections and negative IgG ELISA results (N = 25). The results showed good diagnostic sensitivity (82%) and excellent specificity (96%). Suggested improvements in the SsRapid™ test include increased diagnostic sensitivity and conversion to the more robust cassette format. Field studies should be performed as well.
| S-EPMC8592336 | biostudies-literature
Project description:ObjectivesThe goal of this study is to evaluate the analytical and clinical performance of a new human immunodeficiency virus antigen and antibody (HIV Ag/Ab) test using light-initiated chemiluminescent assay (LiCA®) and compare it with the well-established Architect® HIV Ag/Ab combo assay in a clinical setting.MethodsWe used banked samples and national reference controls to identify the ability to detect HIV Ag/Ab and different viral subtypes. Thirteen seroconversion panels were tested to evaluate early detection of HIV. A total of 21,042 patient samples were collected to compare the diagnostic performance of LiCA® with Architect®. Screening-reactive results were confirmed by Western blotting and nucleic acid testing.ResultsTotal imprecision was within 2.49%-6.56%. The C5-C95 interval was within -10.20%-7.67% away from C50. The limit of detection for p24 antigen was <1.00 IU/mL. Using national reference panels and banked sample pools, LiCA® successfully detected all negative and positive controls in line with the criteria, and all HIV-positive specimens containing different viral subtypes. In 13 seroconversion panels, LiCA® detected reactive results on average 5.73 days (95% CI: 3.42-8.04) after the initial RNA test results were confirmed positive, which was 1.27 days earlier (-3.75 to 1.21) compared to Architect®. Paired comparisons in 21,042 clinical patient samples demonstrated that LiCA® detected HIV Ag/Ab with a slightly better performance in sensitivity (100.00% vs. 99.65%), specificity (99.85% vs. 99.81%), negative predictive value (NPV, 100.00% vs. 99.99%), and positive predictive value (PPV, 89.84% vs. 87.85%) than Architect®. Total agreement between two assays was 99.67% with a kappa value of 0.89.ConclusionLiCA® HIV Ag/Ab is a precise and highly sensitive assay for measuring HIV-1 p24 antigen and HIV-1/2 antibodies with differentiated S/Co values of Ag/Ab. The assay is appropriate for use in the clinical routine test for the early detection of HIV.
| S-EPMC11825764 | biostudies-literature
Project description:Human endogenous retrovirus type K (HERV-K) transcripts are upregulated in the plasma of HIV-infected individuals and have been considered as targets for an HIV vaccine. We evaluated cynomolgus macaque endogenous retrovirus (CyERV) mRNA expression by RT-qPCR in PBMCs isolated from a cohort of animals previously utilized in a live attenuated SIV vaccine trial. CyERV env transcript levels decreased following vaccination (control and vaccine groups) and CyERV env and gag mRNA expression was decreased following acute SIV-infection, whereas during chronic SIV infection, CyERV transcript levels were indistinguishable from baseline. Reduced susceptibility to initial SIV infection, as measured by the number of SIV challenges required for infection, was associated with increased CyERV transcript levels in PBMCs. In vitro analysis revealed that SIV infection of purified CD4(+) T-cells did not alter CyERV gene expression. This study represents the first evaluation of ERV expression in cynomolgus macaques following SIV infection, in an effort to assess the utility of cynomolgus macaques as an animal model to evaluate ERVs as a target for an HIV/SIV vaccine. This non-human primate model system does not recapitulate what has been observed to date in the plasma of HIV-infected humans suggesting that further investigation at the cellular level is required to elucidate the impact of HIV/SIV infection on endogenous retrovirus expression.
| S-EPMC3387136 | biostudies-literature
Project description:Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS) are potentially life-threatening cutaneous reactions caused by several drugs. Recently, a number of genes encoding for human antigen presenting proteins, HLA alleles, have been discovered as valid pharmacogenetic markers for prediction of these life-threatening reactions. This study was aimed to determine the distribution of HLA alleles including the HLA class I and class II genes in 183 unrelated individuals of a Thai population using high resolution HLA genotyping in order to obtain 2-field data (4-digit resolution) and compare the frequencies of the HLA alleles that have been proposed as markers of SCARs with other ethnics. Results revealed a high prevalence of pharmacogenetic markers of drug-induced SCARs e.g., B*13:01 for dapsone; B*15:02 for carbamazepine and oxcarbazepine; B*58:01, A*33:03 and C*03:02 for allopurinol; C*08:01, C*14:02 and DRB1*12:02 for co-trimoxazole. Whereas, low prevalence of pharmacogenetic markers of SCARs induced by abacavir, B*57:01 and phenytoin, B*56:02/B*56:04 were noticed. The allele frequencies of B*13:01, B*15:02, and B*58:01 observed in a Thai population were significantly higher than those reported in Japanese and Caucasian populations. Similar to those observed in other Southeast Asian populations, low frequencies of A*31:01 and B*57:01 alleles were noted in the study population. Based on the frequencies of HLA pharmacogenetic markers, Thai and other Southeast Asian populations may at higher risk of drug-induced SCARs compared with Caucasian population.
| S-EPMC6087736 | biostudies-literature