Suchergebnisse

IntroductionHIV infection impairs maintenance of immunological memory, yet few studies of HIV‐positive adults receiving 7‐valent pneumococcal conjugate vaccine (PCV7) have followed them beyond the first year. We determined and compared the durability of serological responses and the clinical outcomes of HIV‐positive adults annually for five years following vaccination with one or two doses of PCV7.MethodsIn this non‐randomized clinical trial, 221 pneumococcal vaccine‐naïve HIV‐positive adults receiving one (n=109) or two doses four weeks apart (n=112) of PCV7 between 2008 and 2010 were longitudinally followed for evaluation of significant serological response and for episodes of pneumonia and invasive pneumococcal disease.ResultsAt the time of vaccination, the two groups were well matched for age, risk factors, combination antiretroviral therapy (cART) coverage, CD4 count and plasma HIV RNA load (PVL). At the end of five years, the CD4 counts for the one‐ and two‐dose groups had increased from 407 and 406 to 550 and 592 cells/µL, respectively, and 82.4 and 81.6% of the participants had fully suppressed PVL. Significant immune responses to ≥2 serotypes persisted for 67.9 vs 78.6%, 64.2 vs 71.4%, 66.1 vs 71.4%, 57.8 vs 69.6% in the second, third, fourth and fifth years after one and two doses of PCV7 in the intention‐to‐treat analysis, respectively. In multivariate analysis, immunization with two doses of PCV7 (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.10 to 2.65, p=0.016), concurrent cART (OR 2.16, 95% CI 1.16 to 4.00, p=0.015) and CD4 proliferation (OR 1.12, 95% CI 1.01 to 1.27, p=0.031) were predictive of persistent serological responses in the fifth year. Only one patient in the one‐dose group had documented pneumococcal pneumonia (non‐bacteraemic) and none had invasive pneumococcal disease in the 6.5 years of follow‐up.ConclusionsOne or two doses of PCV7 achieve durable seroprotective responses in HIV‐treated participants; however, two doses may be more robust than one dose in a larger study population or in real‐world populations with less cART coverage.

IntroductionThe incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource‐rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994–2000, 2.29 in 2001–2005 to 10.13 per 1000 person‐years of follow‐up (PYFU) in 2006–2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT) service at a University Hospital.MethodsBetween May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third‐generation enzyme immunoassay. A nested case‐control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013.ResultsDuring the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV‐negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76–4.94); the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05–4.51) in 2006–2009, to 3.33 per 1000 PYFU (95% CI, 0.86–5.80) in 2010–2011, to 4.94 per 1000 PYFU (95% CI, 0.99–8.99) in 2012–2013. In case‐control study, HCV seroconverters were more likely to have HIV‐infected partners, recent syphilis and a Rapid Plasma Reagin (RPR) titre of 4 or greater. In multivariate analysis, having HIV‐infected partners remained as the only independent associated factors with HCV seroconversion (AOR, 6.931; 95% CI, 1.064–45.163). Phylogenetic analysis revealed transmission pairs and clusters, with most clustered sequences derived from MSM.ConclusionsSimilar to the observation among HIV‐infected patients who are not IDUs, increasing trends of recent HCV infection also occur among the individuals who sought VCT services in Taiwan. Having HIV‐infected partners is independently associated with recent HCV seroconversion.

IntroductionThe total case number of persons who are newly diagnosed with HIV continues to increase in Taiwan and men who have sex with men (MSM) have re‐emerged as the leading risk group for HIV transmission. In this study, we aimed to estimate the incidence rate of HIV infection among those individuals who sought voluntary counselling and testing (VCT) service at a university hospital.MethodsBetween 1 April, 2006 and 31 December, 2013, 18,246 tests for HIV antibody were performed among 12143 individuals at the VCT service. A total of 2157 individuals who tested negative for anti‐HIV antibody had subsequent follow‐up tests at the same VCT service, which composed the study population for estimation of incidence rate of recent HIV infection. The BED assays were used to identify recent HIV infections that occurred within the previous six months before seeking VCT service.ResultsDuring the 6.5‐year study period, 647 individuals were diagnosed as being HIV‐positive, with an overall HIV seroprevalence of 3.55% (95% CI 3.27–3.82). The overall incidence rate of HIV infection was estimated 4.13 per 100 person‐years of follow‐up (95% CI 3.67–4.69 per 100 person‐years of follow‐up). MSM had an estimated 10‐fold higher seroprevalence and seroincidence of HIV than heterosexuals. Of 647 clients testing positive for HIV, 603 clients were MSM (93.2%) and 477 patients (70.8%) subsequently sought HIV care at the hospital; 226 (47.4%) were diagnosed as having recent HIV infections by the BED assay, while 244 (51.2%) long‐term infection and 7 without data by the BED assay. Of those patients, 173 (75.6%) and 178 patients (73.0%) with recent HIV infection and long‐term infection had data of transmitted drug resistance mutations, respectively. The prevalence of transmitted drug resistance mutations to any class of antiretroviral therapy was 9.0% and 10.6% (p=0.68), respectively, of the HIV‐1 strains from the patients with recent HIV infection and long‐term infection, respectively.ConclusionsThe seroincidence rate of HIV among persons seeking VCT was estimated 4.13 per 100 person‐years of follow‐up. The prevalence of transmitted drug resistance to any class of antiretroviral agents was similar between those who were recently infected with HIV and those who had long‐term infection in Taiwan.

IntroductionWide inter‐patient variation of plasma efavirenz (EFV) concentrations has been observed, and a substantial proportion of HIV‐positive patients may have unnecessarily higher plasma EFV concentrations than recommended while receiving EFV‐containing combination antiretroviral therapy (cART) at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV has recently been demonstrated to be as efficacious as the recommended 600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We aimed to use a therapeutic drug monitoring (TDM)‐guided strategy to optimize the EFV dose in HIV‐positive Taiwanese patients.Materials and MethodsThe plasma EFV concentrations at 12 hours (C12) after taking the previous dose were determined among HIV‐positive adults who had received EFV‐containing cART with viral suppression (plasma HIV RNA load (PVL) <200 copies/mL). For those with EFV C12 >2.0 mg/L, EFV (Stocrit, MSD) was reduced to half a tablet daily. Determinations of EFV C12 were repeated 4–12 weeks after switch using high‐performance liquid chromatography. CYP2B6 G516T polymorphisms were determined using polymerase‐chain‐reaction restriction fragment‐length polymorphism.ResultsBetween April 2013 and June 2014, 111 patients (95.5% male; mean age, 39 years; 96.4% with PVL <40 copies/ml; 26.4% HBsAg‐positive and 7.5% anti‐HCV‐positive) with plasma C12 efavirenz >2.0 mg/L were switched to a reduced dose (1/2# hs) of EFV; 45.5% of them had CYP2B6 G516T or TT genotypes; and 32.4% weighed 60 kg or less. The mean baseline EFV C12 before switch was 3.65 mg/L (interquartile range (IQR), 2.62–4.17) for 111 patients, which decreased to 1.96 mg/L (IQR, 1.53–2.33) for 64 patients who had completed follow‐up of C12 EFV 4 weeks after switch, with a reduction of 49.4% (IQR, 38.9–57.0%). As of 10 July, 2014, all of the 38 patients (100%) who had completed at least one follow‐up of PVL achieved undetectable PVL (<40 copies/ml) following switch to a reduced dose of EFV after a mean observation of 13 weeks (IQR, 7–15 weeks).ConclusionsSwitch to cART containing a half tablet of EFV (1/2#) in HIV‐positive Taiwanese patients with higher plasma EFV concentrations who had achieved viral suppression could maintain successful viral suppression with the guidance of TDM.